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A major consequence of insulin binding its receptor on fat and muscle cells is the stimulation of glucose transport into these tissues. This is achieved through an increase in the exocytic trafficking rate of the facilitative glucose transporter GLUT4 from intracellular stores to the cell surface. Delivery of GLUT4 to the cell surface requires the formation of functional SNARE complexes containing Syntaxin 4, SNAP23, and VAMP2. Insulin stimulates the formation of these complexes and concomitantly causes phosphorylation of Syntaxin 4. Here, we use a combination of biochemistry and cell biological approaches to provide a mechanistic link between these observations. We present data to support the hypothesis that Tyr-115 and Tyr-251 of Syntaxin 4 are direct substrates of activated insulin receptors, and that these residues modulate the protein's conformation and thus regulate the rate at which Syntaxin 4 forms SNARE complexes that deliver GLUT4 to the cell surface. This report provides molecular details on how the cell regulates SNARE-mediated membrane traffic in response to an external stimulus.

Background/aims: This aim of this audit was to assess the extent of serum calcium testing and the frequency of hypercalcaemia in the primary care setting. We also assessed the appropriateness of subsequent investigations with repeat serum calcium and PTH testing if hypercalcaemia was identified., Methods: All laboratory requests for adjusted calcium and PTH samples sent from primary care in Glasgow were analysed over a 12 month period. This covered approximately 125 GP practices and a patient population of over 590,000., Results: There were 78,845 requests for adjusted calcium and 2053 PTH requests from 62,745 patients aged 16-105 years (median age 57, IQ range 30 years). Of these requests 1423 (2.3%) of patients had biochemical evidence of hypercalcaemia (adjusted calcium ≥ 2.61 mmol/L). Of the 1423 patients with hypercalcaemia, 368 patients (45.8%) had a single raised calcium level that was within the normal range on repeat testing. Of the 400 patients with persistent hypercalcaemia on 2 or more samples, 210 (52.5%) had a PTH measured. Eight patients had a PTH < 2.0 pmol/L, whilst 202 (96.1%) had a PTH ≥ 2.0 pmol/L (range 2.1-106.1 pmol/L)., Conclusions: Serum calcium was checked in 10.6% of the population per year within primary care. In the 2.4% with a raised calcium on initial testing, approximately half (45.8%) will normalise on repeat testing. Of those who remained persistently hypercalcaemic, only half (52.5%) had a PTH measured and the majority (96.1%) were in keeping with primary hyperparathyroidism being the most common cause of hypercalcaemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

This paper serves as an update to the previous RESNA Position on the Application of Power Wheelchairs for Pediatric Users with more current and additional scientific literature. This document contains typical clinical applications and best evidence from the literature supporting the application of power mobility (PM) for young children and to assist practitioners in decision-making and justification. It is RESNA' s position that age, limited vision or cognition, behavioral issues, and the ability to walk or propel a manual wheelchair short distances should not, in and of themselves, be used as discriminatory factors against providing PM for children. RESNA recommends early utilization of PM for children with mobility limitations as medically necessary, to promote integration and psycho-social development, reduce passive dependency, and to enhance participation, function, and independence.

Adipocytes are key to metabolic regulation, exhibiting insulin-stimulated glucose transport that is underpinned by the insulin-stimulated delivery of glucose transporter type 4 (SLC2A4, also known and hereafter referred to as GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, and increase cell surface GLUT4 levels. Adipocytokines, such as adiponectin, are secreted via a similar mechanism. We used genome editing to knock out syntaxin-4, a protein reported to mediate fusion between GLUT4-containing vesicles and the plasma membrane in 3T3-L1 adipocytes. Syntaxin-4 knockout reduced insulin-stimulated glucose transport and adiponectin secretion by ∼50% and reduced GLUT4 levels. Ectopic expression of haemagglutinin (HA)-tagged GLUT4 conjugated to GFP showed that syntaxin-4-knockout cells retain significant GLUT4 translocation capacity, demonstrating that syntaxin-4 is dispensable for insulin-stimulated GLUT4 translocation. Analysis of recycling kinetics revealed only a modest reduction in the exocytic rate of GLUT4 in knockout cells, and little effect on endocytosis. These analyses demonstrate that syntaxin-4 is not always rate limiting for GLUT4 delivery to the cell surface. In sum, we show that syntaxin-4 knockout results in reduced insulin-stimulated glucose transport, depletion of cellular GLUT4 levels and inhibition of adiponectin secretion but has only modest effects on the translocation capacity of the cells. This article has an associated First Person interview with Hannah L. Black and Rachel Livingstone, joint first authors of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD)., Aim: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab., Results: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure., Conclusion: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: The regulated delivery of the glucose transporter GLUT4 from intracellular stores to the plasma membrane underpins insulin-stimulated glucose transport. Insulin-stimulated glucose transport is impaired in skeletal muscle of patients with type-2 diabetes, and this may arise because of impaired intracellular trafficking of GLUT4. However, molecular details of any such impairment have not been described. We hypothesized that GLUT4 and/or levels of proteins involved in intracellular GLUT4 trafficking may be impaired in skeletal muscle in type-2 diabetes and tested this in obese individuals without and without type-2 diabetes., Methods: We recruited 12 participants with type-2 diabetes and 12 control participants. All were overweight or obese with BMI of 25-45 kg/m 2 . Insulin sensitivity was measured using an insulin suppression test (IST), and vastus lateralis biopsies were taken in the fasted state. Cell extracts were immunoblotted to quantify levels of a range of proteins known to be involved in intracellular GLUT4 trafficking., Results: Obese participants with type-2 diabetes exhibited elevated fasting blood glucose and increased steady state glucose infusion rates in the IST compared with controls. Consistent with this, skeletal muscle from those with type-2 diabetes expressed lower levels of GLUT4 (30%, p = .014). Levels of Syntaxin4, a key protein involved in GLUT4 vesicle fusion with the plasma membrane, were similar between groups. By contrast, we observed reductions in levels of Syntaxin16 (33.7%, p = 0.05), Sortilin (44%, p = .006) and Sorting Nexin-1 (21.5%, p = .039) and -27 (60%, p = .001), key proteins involved in the intracellular sorting of GLUT4, in participants with type-2 diabetes., Conclusions: We report significant reductions of proteins involved in the endosomal trafficking of GLUT4 in skeletal muscle in obese people with type 2 diabetes compared with age- and weight-matched controls. These abnormalities of intracellular GLUT4 trafficking may contribute to reduced whole body insulin sensitivity., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Introduction: In the management of acute hospital admissions during the COVID-19 pandemic, safe patient cohorting depends on robust admission diagnostic strategies. It is essential that screening strategies are sensitive and rapid, to prevent nosocomial transmission of COVID-19 and maintain patient flow., Methods: We retrospectively identified all COVID-19 positive and suspected cases at our institution screened by reverse transcription polymerase chain reaction (RT-PCR) between 4 April and 28 June 2020. Using RT-PCR positivity within 7 days as our reference standard, we assessed sensitivity and net-benefit of three admission screening strategies: single admission RT-PCR, composite admission RT-PCR and CXR and repeat RT-PCR with 48 h., Results: RT-PCR single-test sensitivity was 91.5% (87.8%-94.4%) versus 97.7% (95.4%-99.1%) (p = 0.025) for RT-PCR/CXR composite testing and 95.1% (92.1%-97.2%) (p = 0.03) for repeated RT-PCR. Net-benefit was 0.83 for single RT-PCR versus 0.89 for RT-PCR/CXR and 0.87 for repeated RT-PCR at 0.02% threshold probability., Conclusion: The RT-PCR/CXR composite testing strategy was highly sensitive when screening patients at the point of hospital admission. Real-world sensitivity of this approach was comparable to repeat RT-PCR testing within 48 h; however, faster facilitating improved patient flow., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Purpose: Excessive accumulation of free fatty acids in the coronary arteries can lead to coronary artery disease (CAD). Quantification of epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) is beneficial to understand its relationship with CAD, hypertension (HT), and diabetes., Material and Methods: This retrospective study included 54 patients who underwent CT coronary angiogram using a multidetector row CT scanner. The EAT and PAT volumes from cardiac images were quantified using Image J software. The severity of CAD was graded using the CAD-RADS score., Results: Twenty-nine patients had no CAD, 21 patients had significant CAD, and 4 patients had insignificant CAD. Out of 21 patients with significant CAD, 14 had involvement of multiple coronary arteries. The EAT and PAT volumes were higher in patients with HT, DM, CAD-present group and significant-CAD-present group, but this was not statistically significant except the PAT volume with respect to diabetes. Significant correlation was found between EAT volume and calcium score ( p = 0.035) and between EAT volume and total cholesterol level ( p = 0.017). Significant differences in the EAT volumes were found in different CAD-RADS categories in the right coronary artery (RCA). From the threshold values, it was observed that CAD can develop in LAD even at lower of EAT and PAT volumes., Conclusions: Quantification of EAT and PAT volumes is beneficial in understanding its relationship with the presence and severity of coronary artery disease and its risk factors., Competing Interests: The authors report no conflict of interest., (© Pol J Radiol 2022.)

Objective: Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes., Research Design and Methods: State-of-the-art metabolic studies were used to characterize Indian individuals with "low BMI diabetes" (LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically matched groups: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy., Results: The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D., Conclusions: These studies are the first to demonstrate that LD individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation., (© 2022 by the American Diabetes Association.)

Purpose: To explore parent and therapist experiences of early power mobility following participation in a Power Mobility Day - a 60-90 min play-based session where children with mobility limitations (<6 years of age) experienced four different early power mobility devices., Method: Participants were purposefully selected from parents and therapists who took part in Power Mobility Days as part of a larger cross-sectional study. One semi-structured interview with each participant was conducted via telephone. Interviews were audio-recorded, transcribed, and analyzed using a content analysis approach., Results: Of 35 adults approached, 11 parents and 11 occupational or physical therapists completed interviews averaging 20 min (range 10-45 min), one week to three months after the session. Participants were parents or therapists of children aged 12 to 48 months of age with a variety of neuromotor diagnoses from different areas of the province. The overarching theme Empowering Children and Families to Explore was developed from themes: Earlier Experiences ; A Novel Introduction ; and Moving Forward ., Conclusion: Power Mobility Days provided a welcoming and inclusive child- and family-led introduction to power mobility. This novel approach may help change both therapists' and families' perception of child potential and perspectives on power mobility as an intervention.IMPLICATIONS FOR REHABILITATION:Exploratory sessions can provide a novel introduction to power mobility interventions.Child enjoyment has a reciprocal impact on family engagement with early power mobility.Experiential child- and family-led learning can increase awareness of power mobility options and possibilities.

Objectives: Risk of hospital-acquired COVID-19 (HA-COVID-19) infection is increased by cohorting infected and non-infected patients together in assessment areas, whist awaiting laboratory PCR results. Molecular point-of-care tests (mPOCT) reduce time to results and improve patient flow but the impact on HA-COVID-19 is unknown., Methods: In this pre and post implementation study patients were evaluated across two time periods: March 1st to August 13th 2020, prior to the introduction of mPOCT in medical admissions areas, and 14th August 2020 to 1st April 2021, after mPOCT introduction. The primary outcome was proportion of HA-COVID-19 infection among all COVID-19 positive patients. Secondary outcome measures included time to SARS-CoV-2 results, length of time spent in the medical assessment area and comparison of local, regional and national proportions of HA-COVID-19., Results: 1988 patients were admitted through the acute medicine admission cohorting area and tested for SARS-CoV-2 prior to introducing mPOCT and 4640 afterwards. Median (IQR) time to SARS-CoV-2 result was 6.5 (2.1-17.9) hours prior to introducing mPOCT and 1.0 (0.8-1.3) hours afterwards (p < 0.0001). Median (IQR) duration in the assessment cohort area was 12.0 (4.8-20.6) hours prior to introduction of POCT and 3.2 (2.0-5.6) hours afterwards (p < 0.0001). The proportion of hospital-acquired COVID-19 cases was 108 (16.5%) of 654 prior to introducing mPOCT compared with 168 (9.4%) of 1782 afterwards, (HR 0.55, 95%CI 0.43-0.70; p < 0.0001). In the period following the introduction of mPOCT up to 1st April 2021 the median proportion of HA-COVID-19 was 13.6% (95%CI 8.2-18.9%) locally, compared with 43.8% (95%CI 37.8-49.9%) for all acute NHS trusts regionally and 30.9% (95%CI 28.4-33.5%) for all NHS trusts nationally., Conclusions: Routine mPOCT for SARS-CoV-2 was associated with reduced time to results, time spent in admission cohort areas, and hospital-acquired COVID-19, compared to laboratory PCR., Competing Interests: Declaration of Competing Interest None TWC has received speaker fees, honoraria, consultancy fees, travel reimbursement, and equipment and consumables free of charge for the purposes of research outside of this submitted study, from BioFire diagnostics and BioMerieux. He has received speaker fees and discounted equipment and consumables from QIAGEN. He has received consultancy fees from Shionogi, Synairgen research, Randox laboratories and Cidara therapeutics. He has been a member of advisory boards for Roche, Janssen and Cepheid. He is a member of two independent data monitoring committees for trials sponsored by Roche. He has acted as the UK chief investigator for a trial sponsored by Janssen, (Copyright © 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Postural management is a multi-disciplinary approach incorporating a comprehensive schedule of daily and night-time positions, equipment and physical activity to help maintain or improve body structures and function and increase activity and participation. Postural management may play a role in preventing contracture, deformity, pain, and asymmetry. This article provides an overview of the evidence supporting use of postural management to positively influence hip health in individuals with cerebral palsy, functioning as Gross Motor Classification System (GMFCS) levels IV or V. Sitting or lying without changing position for more than 8 hours, unsupported supine lying and asymmetrical or windswept postures are associated with pain and hip subluxation/dislocation. Although high-quality experimental research is still limited by many factors, there is limited evidence of harm, and most individuals at GMFCS IV or V require positioning supports to enable participation and function and ease caregiving. Clinical recommendations combining research and clinical opinion support the early use of comfortable positioning routines and/or equipment to reduce time spent in sustained asymmetrical or potentially harmful sitting and lying positions. Supported standing, active weightbearing and stepping are recommended to promote active movement and position change when possible, depending on individual, family and caregiver routines and preferences.

Objectives: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study., Methods: This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202,012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as the dominant strain)., Results: Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47,[0.27,0.79],p = 0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86,[0.64, 1.15],p = 0.308)., Conclusions: The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new treatments and ongoing concern over new COVID-19 variants., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To explore the views of paediatric occupational therapists and physical therapists in Canada and the USA related to (1) the rationale for the age at which power mobility is considered for children and (2) the cognitive skills considered when trialling power mobility. Materials and methods: This study was part of a larger web-based survey study and analyzed responses to two open-ended survey questions: one related to age and one related to cognitive skills. Data were analyzed using the constant comparative method. Results: Analysis revealed four unique themes in the question related to age: (1) 'Power Mobility Should be Introduced at a Specific Age or Stage'; (2) 'Child Requirements'; (3) 'Developmental Impact of All Forms of Independent Mobility'; and (4) 'Benefits of Power Mobility'. In the question concerning cognitive skills, two unique themes were identified: 'Cognitive Skill Requirements?' and 'Non-Cognitive Requirements'. Two additional themes were identified in both questions: ('Non-child Requirements' and 'Power Mobility Trials, Use, and Options Are Dependent on Age and Goal'). Conclusions: Data indicate wide variability in respondents' views related to the provision of power mobility. Additional research is needed to explore both therapists' reasoning regarding power mobility use for children and how to best facilitate knowledge translation in this area.Implications for RehabilitationWide variability exists related to the provision of power mobility for children.Children's age or stage in life influences therapists' consideration of power mobility.Many respondents considered cognitive skills when trialling power mobility but some did not.

In 2011, the James Lind Alliance published a 'top 10' list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long-term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the 'glucose variability hypothesis'. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross-sectional, and based on 'finger-prick' glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short-term glucose variability on long-term complications. Few other high-quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA 1c and avoidance of hypoglycaemia., (© 2019 Diabetes UK.)

Aim: To explore the views and practices of paediatric occupational therapists and physical therapists in Canada and the USA regarding the implementation of power mobility for children with mobility limitations., Method: This descriptive study utilized a web-based survey that included questions pertaining to therapists' decisions to trial and use power mobility, agreement or disagreement with statements developed from published practice considerations regarding power mobility, and the frequency of performing tasks related to power mobility prescription and training., Results: Most respondents reported that child characteristics (e.g. cognition, safety awareness) were important factors in decision-making about power mobility, whereas other child characteristics (e.g. communication abilities, age) were not as important. Family resources and home accessibility were also not considered important. The average age at which respondents considered power mobility for children was 2 years 3 months. The majority of respondents agreed with statements developed from published practice considerations and most frequently performed various power mobility tasks twice a year or less., Interpretation: Although most respondents appeared to have positive views regarding power mobility, few appeared to actively perform power mobility tasks in their practice. Resources to support therapists in the early introduction of power mobility may be beneficial., What This Paper Adds: Occupational and physical therapists positively view early introduction of power mobility for children with mobility limitations. Few therapists actively provide early power mobility experiences. Power mobility training and monitoring power mobility devices are important therapist roles., (© 2018 Mac Keith Press.)

Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial infarction, stroke, and peripheral vascular disease) and microvascular (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an effective strategy for preventing microvascular complications, but the extent to which it can reduce CV complications is less certain. Glucagon-like peptide-1 (GLP-1) agonists are potent glucose-lowering agents but also have potentially beneficial effects on other traditional (body weight, blood pressure (BP), and LDL cholesterol) and non-traditional risk factors (low grade inflammation and endothelial dysfunction). The results of four large CV outcome trials with GLP-1 agonists are now available. These have compared lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), and long-acting exenatide (EXSCEL) with placebo and standard of care over 2-4 years; four others (including with dulaglutide and albiglutide) are ongoing. LEADER and SUSTAIN-6 have demonstrated reductions in rates of major adverse CV events with active GLP-1 treatment but ELIXA and EXSCEL have not. In this review, we discuss the mechanisms by which GLP-1 receptor agonists act on the CV system and the design and conduct of these trials. Contrary to the assertions that (a) all GLP-1 agonists reduce CV disease in T2D but to different extents or (b) the magnitude of CV protection is predominantly related to glucose-lowering, we argue that CV benefit is specific to agents that provide longer acting agonism at the GLP-1 receptor. The mechanisms involve reduction in body weight and BP, and lowering of LDL-cholesterol and glucose, but pleiotropic effects-including suppression of low grade inflammation, vasodilation, and natriuresis-are also likely relevant., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associates with lower insulin secretion., Subjects/methods: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices. Magnetic resonance imaging and 1 H-magnetic resonance spectroscopy were used to measure body fat distribution and ectopic fat content in liver and pancreas., Results: In age-, sex- and BMI-adjusted analyses, total and high-molecular-weight adiponectin were the strongest negative predictors of fasting beta-cell function (BCF; β=-0.403, p=0.0003 and β=-0.237, p=0.01, respectively) and adaptation index (AI; β=-0.210, p=0.006 and β=-0.133, p=0.02, respectively). Circulating TG, but not pancreatic fat content, related positively to BCF (β=0.375, p<0.0001) and AI (β=0.192, p=0.003). Similar results were obtained for the disposition index (DI)., Conclusions: The association of serum lipids and adiponectin with beta-cell function may represent a compensatory response to adapt for lower insulin sensitivity in nondiabetic humans., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate evidence supporting physical and occupational therapy interventions used to improve sensory and motor outcomes for children 0-6 years with central hypotonia., Methods: Four electronic databases were searched from 1996 to March 2017. Level of evidence and study conduct was evaluated using American Academy of Cerebral Palsy and Developmental Medicine criteria. Traffic lighting classification identified interventions that were green (proven effective), yellow (possibly effective) or red (proven ineffective or contraindicated)., Results: Thirty-seven articles were included. Nine studies measured orthotic interventions while four distinct studies published over nine articles measured treadmill interventions. Remaining studies measured impact of compression garments, massage, motor and sensori-motor interventions, positioning and mobility interventions., Conclusions: Green light evidence supports treadmill training (to promote ambulation and gait characteristics) and massage (to positively affect muscle tone, motor development and use of vision) for infants with Down syndrome. These interventions are considered Yellow (possibly effective) for other populations. Green light evidence supports impact of orthoses on foot alignment for ambulatory children with hypotonia, while impact on gait characteristics is Yellow light and motor development may be negatively impacted (Red light) in pre-ambulatory children. All other interventions rated Yellow (possibly effective) and therapists should monitor using sensitive outcome measures.

Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble N -ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. We will describe how these proteins are controlled in a range of regulated trafficking events, with particular emphasis on the insulin-stimulated delivery of glucose transporters to the surface of adipose and muscle cells. Here, we focus on a few examples of SNARE phosphorylation which exemplify distinct ways in which SNARE machinery phosphorylation may regulate membrane fusion., (© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: In 2017, the Australian Government funded the update of the National Physical Activity Recommendations for Children 0-5 years, with the intention that they be an integration of movement behaviours across the 24-h period. The benefit for Australia was that it could leverage research in Canada in the development of their 24-h guidelines for the early years. Concurrently, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group published a model to produce guidelines based on adoption, adaption and/or de novo development using the GRADE evidence-to-decision framework. Referred to as the GRADE-ADOLOPMENT approach, it allows guideline developers to follow a structured and transparent process in a more efficient manner, potentially avoiding the need to unnecessarily repeat costly tasks such as conducting systematic reviews. The purpose of this paper is to outline the process and outcomes for adapting the Canadian 24-Hour Movement Guidelines for the Early Years to develop the Australian 24-Hour Movement Guidelines for the Early Years guided by the GRADE-ADOLOPMENT framework., Methods: The development process was guided by the GRADE-ADOLOPMENT approach. A Leadership Group and Consensus Panel were formed and existing credible guidelines identified. The draft Canadian 24-h integrated movement guidelines for the early years best met the criteria established by the Panel. These were evaluated based on the evidence in the GRADE tables, summaries of findings tables and draft recommendations from the Canadian Draft Guidelines. Updates to each of the Canadian systematic reviews were conducted and the Consensus Panel reviewed the evidence for each behaviour separately and made a decision to adopt or adapt the Canadian recommendations for each behaviour or create de novo recommendations. An online survey was then conducted (n = 302) along with five focus groups (n = 30) and five key informant interviews (n = 5) to obtain feedback from stakeholders on the draft guidelines., Results: Based on the evidence from the Canadian systematic reviews and the updated systematic reviews in Australia, the Consensus Panel agreed to adopt the Canadian recommendations and, apart from some minor changes to the wording of good practice statements, keep the wording of the guidelines, preamble and title of the Canadian Guidelines. The Australian Guidelines provide evidence-informed recommendations for a healthy day (24-h), integrating physical activity, sedentary behaviour (including limits to screen time), and sleep for infants (<1 year), toddlers (1-2 years) and preschoolers (3-5 years)., Conclusions: To our knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been used. Following this approach, the judgments of the Australian Consensus Panel did not differ sufficiently to change the directions and strength of the recommendations and as such, the Canadian recommendations were adopted with very minor alterations. This allowed the Guidelines to be developed much faster and at lower cost. As such, we would recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines, with all supporting materials and developed using a transparent process, is available. Other countries may consider using this approach when developing and/or revising national movement guidelines.

Metformin is quite frequently used off-label in type 1 diabetes to limit insulin dose requirement. Guidelines recommend that it can improve glucose control in those who are overweight and obese but evidence in support of this is limited. Recently-published findings from the REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL) trial suggest that metformin therapy in type 1 diabetes can reduce atherosclerosis progression, weight and LDL-cholesterol levels. This provides a new perspective on metformin therapy in type 1 diabetes and suggests a potential role for reducing the long-term risk of cardiovascular disease.

Background: There is a lack of understanding of the factors that influence independent mobility and participation in meaningful activities. The purpose of this study was to analyse physical factors influencing independent use of manual and power wheelchairs in a total population of children with cerebral palsy (CP)., Methods: A cross-sectional study based on the most recent examination of all children with CP, born 2002-2013, reported into the Swedish cerebral palsy registry (CPUP), from January 2012 to June 2014. There were 2328 children (58 % boys, 42 % girls), aged 0-11 years, at all levels of gross motor function and hand function. Hazard ratios adjusted for age and sex were used to calculate the risk for not being able to self-propel based on Gross Motor Function Classification System (GMFCS) levels, upper extremity range of motion and hand function including Manual Ability Classification System (MACS), House functional classification system, Thumb-in-palm deformity, Zancolli (spasticity of wrist/finger flexors) and bimanual ability., Results: In total 858 children used wheelchairs outdoors (692 manual, 20 power, 146 both). Only 10 % of the 838 children self-propelled manual wheelchairs, while 90 % were pushed. In contrast 75 % of the 166 children who used power mobility outdoors were independent. Poor hand function was the greatest risk factor for being unable to self-propel a manual wheelchair, while classification as GMFCS V or MACS IV-V were the greatest risk factors for not being able to use a power wheelchair independently., Conclusions: The majority of children with CP, aged 0-11 years did not self-propel manual wheelchairs regardless of age, gross motor function, range of motion or manual abilities. Power mobility should be considered at earlier ages to promote independent mobility for all children with CP who require a wheelchair especially outdoors.

The purpose of this study was to evaluate the inertial properties and forces required to initiate movement on two different surfaces in a sample of three commonly prescribed gait trainers. Tests were conducted in a laboratory setting to compare the Prime Engineering KidWalk, Rifton Pacer, and Snug Seat Mustang with and without a weighted anthropometric test dummy configured to the weight and proportions of a 4-year-old child. The Pacer was the lightest and the KidWalk the heaviest while footprints of the three gait trainers were similar. Weight was borne fairly evenly on the four casters of the Pacer and Mustang while 85% of the weight was borne on the large wheels of the mid-wheel drive KidWalk. These differences in frame style, wheel, and caster style and overall mass impact inertial properties and forces required to initiate movement. Test results suggest that initiation forces on tile were equivalent for the Pacer and KidWalk while the Mustang had the highest initiation force. Initiation forces on carpet were lowest for the KidWalk and highest for the Mustang. This initial study of inertia and movement initiation forces may provide added information for clinicians to consider when selecting a gait trainer for their clients.

Aims: To assess young healthy men from rural India, who had normal or low birth weights, using magnetic resonance spectroscopy to determine the potential differences in ectopic fat storage between birth weight groups, and to determine if ectopic fat storage was associated with insulin resistance in this population., Methods: A total of 54 lean men with normal birth weight and 49 lean men with low birth weight (age range 18-22 years) from rural India were recruited. All the men underwent anthropometry, magnetic resonance spectroscopy, a hyperinsulinaemic-euglycaemic clamp and a dual-energy X-ray absorptiometry., Results: The median (interquartile range) values for hepatic cellular lipids, intramyocellular lipids and extramyocellular lipids, measured using magnetic resonance spectroscopy were 0.76 (0.1-1.8)%, 1.27 (1.0-2.3)% and 1.89 (1.3-3.2)%, respectively, for the normal birth weight group and 0.4 (0.1-1.3)%, 1.38 (0.9-2.2)% and 2.07 (1.2-2.8)%, respectively, for the low birth weight group (P > 0.05). No difference in ectopic fat storage was observed between the low and normal birth weight groups, with or without adjustment for age and total fat percentage. Homeostatic model assessment of insulin resistance values were not associated with hepatic cellular, intramyocellular or extramyocellular lipid content in any of the groups. Total fat percentage was the only independent predictor of intramyocellular and extramyocellular lipid content., Conclusion: Young and lean men from rural India with low birth weight were not observed to have ectopic fat storage in the liver or muscle, and the amount of liver and muscle fat was unrelated to insulin resistance. Older age and/or an urban affluent lifestyle may be required to show a potential role of ectopic fat storage on insulin resistance in Indian people with low or normal birth weight., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Purpose: Lack of time, competencies, resources and supports are documented as barriers to evidence-based practice (EBP). This paper introduces a recently developed web-based toolkit designed to assist interprofessional clinicians in implementing EBP within a paediatric rehabilitation setting., Methods: EBP theory, models, frameworks and tools were applied or adapted in the development of the online resources, which formed the basis of a larger support strategy incorporating interactive workshops, knowledge broker facilitation and mentoring., Results: The highly accessed toolkit contains flowcharts with embedded information sheets, resources and templates to streamline, quantify and document outcomes throughout the EBP process. Case examples relevance to occupational therapy and physical therapy highlight the utility and application of the toolkit in a clinical paediatric setting. Workshops were highly rated by learners for clinical relevance, presentation level and effectiveness. Eight evidence syntheses have been created and 79 interventions have been evaluated since the strategy's inception in January 2011., Conclusions: The toolkit resources streamlined and supported EBP processes, promoting consistency in quality and presentation of outputs. The online toolkit can be a useful tool to facilitate clinicians' use of EBP in order to meet the needs of the clients and families whom they support. Implications for Rehabilitation A comprehensive online EBP toolkit for interprofessional clinicians is available to streamline the EBP process and to support learning needs regardless of competency level. Multi-method facilitation support, including interactive education, e-learning, clinical librarian services and knowledge brokering, is a valued but cost-restrictive supplement to the implementation of online EBP resources. EBP resources are not one-size-fits-all; targeted appraisal tools, models and frameworks may be integrated to improve their utility for specific sectors, which may limit them for others.

Background: Sitting for more than 8 h a day has been shown to negatively impact health and mortality while standing is the recommended healthier alternative. Home-based standing programs are commonly recommended for adults who cannot stand and/or walk independently. The aim of this systematic review is to review effectiveness of home-based standing programs for adults with neurological conditions including stroke and spinal cord injury; and to provide dosage guidelines to address body structure and function, activity and participation outcomes., Methods: Eight electronic databases were searched, including Cochrane Library databases, MEDLINE, CINAHL and EMBASE. From 376 articles, 36 studies addressing impact of a standing intervention on adults with sub-acute or chronic neurological conditions and published between 1980 and September 2015 were included. Two reviewers independently screened titles, reviewed abstracts, evaluated full-text articles and rated quality and strength of evidence. Evidence level was rated using Oxford Centre for Evidence Based Medicine Levels and quality evaluated using a domain-based risk-of-bias rating. Outcomes were divided according to ICF components, diagnoses and dosage amounts from individual studies. GRADE and the Evidence-Alert Traffic-Lighting system were used to determine strength of recommendation and adjusted in accordance with risk-of-bias rating., Results: Stronger evidence supports the impact of home-based supported standing programs on range of motion and activity, primarily for individuals with stroke or spinal cord injury while mixed evidence supports impact on bone mineral density. Evidence for other outcomes and populations is weak or very weak., Conclusions: Standing should occur 30 min 5 times a week for a positive impact on most outcomes while 60 min daily is suggested for mental function and bone mineral density.

Objective: To summarize and critically appraise evidence regarding use of gait trainers (walkers providing trunk and pelvic support) at home or school with children who are unable to walk independently or with hand-held walkers., Data Sources: Searches were performed in seven electronic databases including EBM Reviews, CINAHL, Medline and EMBASE for publications in English from database inception to November 2014., Review Methods: Included studies involved at least one child with a mobility limitation and measured an outcome related to gait trainer use. Articles were appraised using American Academy of Cerebral Palsy and Developmental Medicine criteria for group and single-subject designs and quality ratings completed for studies rated levels I-III. The PRISMA statement was followed with inclusion criteria set a priori. Two reviewers independently screened titles, abstracts and full-text articles., Results: Seventeen studies involving 182 children were included. Evidence from one small randomized controlled trial suggests a non-significant trend toward increased walking distance while the other evidence level II study (concurrent multiple baseline design) reports increased number of steps. Two level III studies (non-randomized two-group studies) report statistically significant impact on mobility level with one finding significant impact on bowel function and an association between increased intervention time and bone mineral density. Remaining descriptive level evidence provides support for positive impact on a range of activity outcomes, with some studies reporting impact on affect, motivation and participation with others., Conclusions: Evidence supporting outcomes for children using gait trainers is primarily descriptive and, while mainly positive, is insufficient to draw firm conclusions., (© The Author(s) 2015.)

Background: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage., Objective: We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans., Design: Young, lean, insulin-sensitive humans (CONs) [mean ± SD body mass index (BMI; in kg/m(2)): 23.2 ± 1.5]; insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 ± 1.7); and type 2 diabetes patients (T2Ds) (BMI: 32.0 ± 2.4) were studied (n = 10/group). T2Ds (61 ± 7 y old) were older (P < 0.001) than were OBEs (31 ± 7 y old) and CONs (28 ± 3 y old). We quantified hepatic γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps., Results: OBEs and T2Ds were similarly insulin resistant (M value: 3.5 ± 1.4 and 1.9 ± 2.5 mg · kg(-1) · min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic γATP concentrations, the maximum postprandial increase of γATP was 6-fold higher in OBEs (0.7 ± 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 ± 0.2 mmol/L; P = 0.09) than in CONs (0.1 ± 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs., Conclusions: Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01229059., (© 2015 American Society for Nutrition.)

Diabetes is becoming more prevalent in the UK and this is represented in the in-patient cohort, such that 1 in 6 hospital patients have diabetes (1). The UK National Diabetes In-Patient Audit in 2012 estimated that 30% of patients experience one episode of hypoglycaemia during admission. Hypoglycaemia is associated with increased morbidity and mortality, and longer length of hospital stay. It is therefore important that hypoglycaemia is managed promptly and effectively to reduce associated morbidity. The Joint British Diabetes Society recommends that all wards should have access to 'Hypo Boxes' (2). We assessed all episodes of hypoglycaemia (<4.0 mmol/l) in the diabetes wards in over a 4 week period. 'Hypo Boxes' were installed to the wards and the appropriateness of treatment and time to correction of hypoglycaemia was re-assessed. Assessment of hypoglycaemia pre-intervention revealed 45 episodes of hypoglycaemia in 14 patients, and 42% (n=19) of episodes were deemed to have been treated appropriately. Only 17.8% of episodes were corrected within 30 minutes, and 33.3% were corrected within 60 minutes. A third of patients (35%) did not have a further blood glucose checked. Following intervention, there was a marked improvement in management. The proportion of appropriately managed episodes increased to 82% (n=35) and management of episodes of severe hypoglycaemia (<3.0 mmol/l) increased to 94%. The time to correction increased with 40% of episodes corrected to >4.0 mmol/l within 30 minutes, and a further 54% between 30-60 minutes. In conclusion, the introduction of 'Hypo Boxes' improved the assessment and management of hypoglycaemia.

Aim: The aim of this study was to critically synthesize qualitative evidence regarding the child and family experience of power mobility, and to examine how this evidence fits with current theoretical concepts., Method: Electronic database/hand searches were undertaken in September 2012 and updated in February 2014. The searches were restricted to qualitative studies published in English before February 2014 that included at least one child under the age of 19 with a disability and described an outcome related to the use of power mobility. Inclusion criteria were set a priori. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. McMaster qualitative review forms were used for quality appraisal., Results: Of 259 titles, 21 met inclusion criteria. From 143 codes, 15 second-order themes were developed using constant comparison and analysis. Three overarching themes emerged: power mobility experience promotes developmental change and independent mobility; power mobility enhances social relationships and engagement in meaningful life experiences; and power mobility access and use is influenced by factors in the physical, social, and attitudinal environment., Interpretation: This qualitative research provides rich and rigorous evidence supporting the benefits of power mobility for children and families. Numerous factors, which warrant careful consideration, influence power mobility access and use., (© 2014 Mac Keith Press.)

Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m(2)) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD(+) levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD(+) boosters can also directly affect skeletal muscle mitochondrial function in humans., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To summarize and critically appraise the evidence related to power mobility use in children (18 years or younger) with mobility limitations., Data Sources: Searches were performed in 12 electronic databases along with hand searching for articles published in English to September 2012 and updated February 2014., Review Methods: The search was restricted to quantitative studies including at least one child with a mobility limitation and measuring an outcome related to power mobility device use. Articles were appraised using American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) criteria for group and single-subject designs. The PRISMA statement was followed with inclusion criteria set a priori. Two reviewers independently screened titles, abstracts and full-text articles. AACPDM quality ratings were completed for levels I-III studies., Results: Of 259 titles, 29 articles met inclusion criteria, describing 28 primary research studies. One study, rated as strong level II evidence, supported positive impact of power mobility on overall development as well as independent mobility. Another study, rated as moderate level III evidence, supported positive impact on self-initiated movement. Remaining studies, rated evidence levels IV and V, provided support for a positive impact on a broad range of outcomes from to International Classification of Functioning (ICF) components of body structure and function, activity and participation. Some studies suggest that environmental factors may be influential in successful power mobility use and skill development., Conclusion: The body of evidence supporting outcomes for children using power mobility is primarily descriptive rather than experimental in nature, suggesting research in this area is in its infancy., (© The Author(s) 2014.)

Purpose: The aims of this study were (i) to establish a robust and fast method to quantify hepatocellular phosphorus compounds in molar concentration on a 3T clinical scanner, (ii) to evaluate its reproducibility, and (iii) to test its feasibility for a use in large cohort studies., Method: Proton-decoupled (31) P magnetic resonance spectroscopy of liver (31) P compounds were acquired on 85 healthy subjects employing image selected in-vivo spectroscopy localization in 13 min of acquisition at 3T. Absolute quantification was achieved using an external reference and double-matching phantoms (inorganic phosphates and adenosine triphosphate (ATP) solutions). Reproducibility of the method was also examined., Results: This method showed a high intra- and interday as well as inter- and intraobserver reproducibility (r > 0.98; P < 0.001), with a high signal to noise ratio (SNR) (i.e., mean SNR of γ-ATP: 16). The mean liver concentrations of 85 healthy subjects were assessed to be 1.99 ± 0.51 and 2.74 ± 0.55 mmol/l of wet tissue volume for Pi and γ-ATP, respectively., Conclusion: This method reliably quantified molar concentrations of liver (31) P compounds on 85 subjects with a short total examination time (∼25 min) on a 3T clinical scanner. Thus, the current method can be readily utilized for a clinical study, such as a large cohort study., (Copyright© 2013 Wiley Periodicals, Inc.)

Context: Hepatic steatosis, defined as increased hepatocellular lipid content (HCL), associates with visceral obesity and glucose intolerance. As exact HCL quantification by 1H-magnetic resonance spectroscopy (1H-MRS) is not generally available, various clinical indices are increasingly used to predict steatosis., Objective: The purpose of this study was to test the accuracy of NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI) and fatty liver index (FLI) against 1H-MRS and their relationships with insulin sensitivity and secretion., Design, Setting and Participants: Ninety-two non-diabetic, predominantly non-obese humans underwent clinical examination, 1H-MRS and an oral glucose tolerance test (OGTT) to calculate insulin sensitivity and β-cell function. Accuracy of indices was assessed from the area under the receiver operating characteristic curve (AROC)., Results: Median HCL was 2.49% (0.62;4.23) and correlated with parameters of glycemia across all subjects. NAFLD-LFS, FLI and HSI yielded AROCs of 0.70, 0.72, and 0.79, respectively, and related positively to HCL, insulin resistance, fasting and post-load β-cell function normalized for insulin resistance. Upon adjustment for age, sex and HCL, regression analysis revealed that NAFLD-LFS, FLI and HSI still independently associated with both insulin sensitivity and β-cell function., Conclusion: The tested indices offer modest efficacy to detect steatosis and cannot substitute for fat quantification by 1H-MRS. However, all indices might serve as surrogate parameters for liver fat content and also as rough clinical estimates of abnormal insulin sensitivity and secretion. Further validation in larger collectives such as epidemiological studies is needed.

Aim: The aim of the study was to support clinicians in recommending and justifying power mobility for children of different ages and abilities, and with different needs. The study comprised three distinct parts: a literature review; a Delphi consensus; and clinical practice considerations., Method: A scoping review of eight electronic databases and manual searches carried out in February 2011 identified 15 themes or transferable messages among 27 articles meeting initial inclusion criteria and these formed the basis of a draft paper. Informal consensus at two international conference presentations refined and modified the paper to include 10 messages supported by 24 articles. The literature review was updated in May 2012 and a modified Delphi process sought to formalize the consensus process with an international panel of 16 expert clinicians and researchers using a priori criteria of 80% agreement., Results: Evidence from studies was classified using the American Academy of Cerebral Palsy and Developmental Medicine guidelines, with evidence from most studies being classified as either level IV or level V, apart from one study each with evidence classified as level II and level III. Expert consensus on the content and wording of nine transferable messages may raise evidence overall to level III., Interpretation: This paper suggests that power mobility may reasonably be considered as an effective and appropriate intervention for children lacking efficient, independent mobility from around 12 months of age including children who may never become competent drivers and children lacking independent mobility only in early childhood., (© 2013 Mac Keith Press.)

Objective: To identify and critically appraise clinical measurement tools used to assess sitting posture, seated postural control or functional abilities for children with motor impairment who are candidates for seating interventions., Data Sources: Searches were run in 15 electronic databases along with hand searching. The search included articles published in English to December 2011., Review Methods: Key terms included: posture, sitting, sitting posture, seated posture, seated postural control, sitting position, seating, wheelchair(s), outcome and assess(ment). The PRISMA statement was followed with inclusion criteria set a priori. Two reviewers independently screened titles, reviewed abstracts and identified full-text articles that met criteria. Data extraction included tool description and clinical utility. Two quality-rating scales were used to evaluate conduct of the studies and psychometric properties of the tools., Results: Of the 497 titles found in the search, 29 full-text articles met the inclusion criteria and 19 tools were identified. Tools represented all components of the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY), with emphasis on body structure and function and activity components. Evidence supporting reliability and validity varied, with small sample sizes influencing quality ratings. Evidence of the tools' reliability was more prevalent than evidence of the tools' validity. Only four tools reported on responsiveness, an important consideration for evaluating change. Little information on clinical utility was provided., Conclusion: Although a number of tools are available, evidence supporting their use for seating interventions is limited, as is the evidence supporting the strength of their measurement properties. Few tools address participation, environmental factors or the child's and family's perspective.

Objective: Low birth weight (LBW) is common in the Indian population and may represent an important predisposing factor for type 2 diabetes (T2D) and the metabolic syndrome. Intensive metabolic examinations in ethnic LBW Asian Indians have been almost exclusively performed in immigrants living outside India. Therefore, we aimed to study the metabolic impact of being born with LBW in a rural non-migrant Indian population., Subjects and Methods: One hundred and seventeen non-migrant, young healthy men were recruited from a birth cohort in a rural part of south India. The subjects comprised 61 LBW and 56 normal birth weight (NBW) men, with NBW men acting as controls. Subjects underwent a hyperinsulinaemic euglycaemic clamp, i.v. and oral glucose tolerance tests and a dual-energy X-ray absorptiometry scan. The parents' anthropometric status and metabolic parameters were assessed., Results: Men with LBW were shorter (167±6.4 vs 172±6.0 cm, P<0.0001), lighter (51.9±9 vs 55.4±7 kg, P=0.02) and had a reduced lean body mass (42.1±5.4 vs 45.0±4.5 kg, P=0.002) compared with NBW controls. After adjustment for height and weight, the LBW subjects had increased diastolic blood pressure (77±6 vs 75±6 mmHg, P=0.01). Five LBW subjects had impaired glucose tolerance. In vivo insulin secretion and peripheral insulin action were similar in both the groups. Mothers of the LBW subjects were 3 cm shorter than the control mothers., Conclusion: Only subtle features of the metabolic syndrome and changes in body composition among LBW rural Indians were found. Whether other factors such as urbanisation and ageing may unmask more severe metabolic abnormalities may require a long-term follow-up.

Time-resolved photoelectron spectroscopy was used to obtain new information about the dynamics of electronic relaxation in gas-phase indole and 5-hydroxyindole following UV excitation with femtosecond laser pulses centred at 249 nm and 273 nm. Our analysis of the data was supported by ab initio calculations at the coupled cluster and complete-active-space self-consistent-field levels. The optically bright (1)L(a) and (1)L(b) electronic states of (1)ππ∗ character and spectroscopically dark and dissociative (1)πσ∗ states were all found to play a role in the overall relaxation process. In both molecules we conclude that the initially excited (1)L(a) state decays non-adiabatically on a sub 100 fs timescale via two competing pathways, populating either the subsequently long-lived (1)L(b) state or the (1)πσ∗ state localised along the N-H coordinate, which exhibits a lifetime on the order of 1 ps. In the case of 5-hydroxyindole, we conclude that the (1)πσ∗ state localised along the O-H coordinate plays little or no role in the relaxation dynamics at the two excitation wavelengths studied.

Purpose: Assessment and training of young children using powered mobility tends to be based on expert opinion although research in this area has recently been completed. This review critiques available research and discusses the studies in relation to theory and expert opinion., Method: A literature review was completed to identify research regarding powered mobility training for children with developmental disabilities. Two recent qualitative studies were identified and their models and assessment tools were compared and discussed with recommendations for clinical practice and research., Results: The focus of the two studies is on a continuum of learning, the reciprocal relationship of trainer and trainee, and impact of the social and attitudinal environment on powered mobility skill development. The assessment tools and training protocols are backed up by motor learning principles and expert opinion. Further research is required to incorporate the tools into clinical practice and to examine additional psychometric properties., Conclusions: Rather than focusing on readiness skills or pass/fail tests, clinicians should explore early mobility options for clients at the beginning of the continuum of learning, reflect on how they relate to and impact on their clients' learning, and set up the environment to facilitate independent learning and exploration.

Two color polarization spectroscopy has been employed to measure the collisional depolarization of OH(A(2)Sigma(+), v = 1) by He and Ar. Complementary experiments using Zeeman quantum beat spectroscopy have also been performed to determine separately the cross sections for rotational energy transfer (RET) out of selected rotational levels of OH(A, v = 0) + Ar, as well as those for elastic depolarization. This has been achieved by dispersing the emission, so as to observe a single fluorescence transition. Elastic depolarization of OH(A) by Ar is found to be significant with that for loss of rotational alignment exceeding that for loss of orientation. In the case of OH(A) + He, the polarization spectroscopy measurements suggest that elastic depolarization plays a relatively minor role in the loss of the polarization signal compared with RET. The experimental data for OH(A) + Ar are compared in detail with the results of quasi-classical trajectory calculations that accommodate the effects of electron spin. These classical calculations are assessed against the results obtained using full close-coupled open shell quantum mechanical scattering methods. Overall the level of agreement between the two experiments, and between experiment and theory, is very reasonable. Surprisingly, at low N the elastic depolarization cross sections for OH(A) + Ar are found to be quite similar in magnitude to those observed for OH(X) + Ar despite the fact that the well depth in the latter system is considerably smaller than that for OH(A)-Ar. However, for OH(A) + Ar the depolarization cross sections are insensitive to N in the range 1-14. It is proposed that this behavior partly reflects the relatively anisotropic nature of the potential energy surface, which exhibits deep wells of different depths at the two linear configurations OH(A)-Ar and Ar-OH(A), and partly the nature of elastic depolarizing collisions, which must occur with a velocity component perpendicular to the plane of rotation of the diatomic molecule.

Background: Studies by individual acupuncture practitioners have given an indication that offering acupuncture in primary care may reduce the need for referral to secondary care and reduce the costs of prescriptions. It would be informative to find out whether these findings can be supported by data from other practices. The aim of this study was to test the feasibility of surveying national data on referrals and prescribing., Methods: Three primary care trusts (PCTs) were selected, and all practices within each trust were sent an email asking whether any member of the primary care team offered acupuncture, and if so how many appointments per week. Data on rates of referral to orthopaedic, physiotherapy, pain and rheumatology clinics were then sought from the PCT, both for the practices offering acupuncture and for the PCT as a whole. Similarly, data on costs of prescriptions for non-steroidal (NSAID) and non-opioid analgesic drugs were obtained from the Prescription Pricing Authority., Results: Out of the 109 practices surveyed, a total of 14 (13%) offered acupuncture services to some extent. There was wide variation in provision between the different PCTs. The eight practices which offered at least one appointment per week for every 2000 registered patients were included in the analysis. The mean values (and SDs) for the three PCTs and for the eight acupuncture practices, respectively, were as follows: for referral to various clinics: orthopaedic 32.3 (16.2) and 27.4 (10.87); pain clinic 1.6 (1.3) and 2.8 (1.6); physiotherapy 13.4 (14.5) and 29.5 (10.0); and rheumatology 4.7 (2.3) and 6.4 (3.0). The mean values for costs of non-opioid analgesics were pound1820 ( pound442) and pound2008 ( pound762); and for NSAIDs were pound4148 ( pound269) and pound4476 ( pound1366), respectively. There were no trends towards a reduction of clinic referral or prescription costs., Conclusions: We have conducted the first survey of the effects of provision of acupuncture in UK general practice, using data provided by the NHS, and uncovered a wide variation in the availability of the service in different areas. We have been unable to demonstrate any consistent differences in the prescribing or referral rates that could be due to the use of acupuncture in these practices. The wide variation in the data means that if such a trend exists, a very large survey would be needed to identify it. However, we discovered inaccuracies and variations in presentation of data by the PCTs which have made the numerical input, and hence our results, unreliable. Thus the practicalities of access to data and the problems with data accuracy would preclude a nationwide survey.

Background: Knowledge of variations in the cerebral venous anatomy and apparent signal abnormalities seen on Magnetic resonance (MR) angiography are essential to avoid over-diagnosis of cerebral venous sinus thrombosis (CVST), while interpreting the MR angiograms., Aims: To evaluate the variations of cerebral venous anatomy and signal abnormalities by using 3D phase contrast MR angiography performed in a 0.5 Tesla MRI scanner., Materials and Methods: One hundred patients who underwent MR imaging and MR angiography examinations at our institution from March 2004 to February 2005, with normal MR imaging of brain were studied retrospectively. Patients with clinical suspicion of CVST and patients who underwent color doppler evaluation for suspected deep vein thrombosis were excluded., Results: The superior sagittal, straight sinus and the internal cerebral veins were visualized in all patients. There was hypoplasia of the right transverse sinus in 13 patients, left transverse sinus in 35 patients, right sigmoid sinus in 6 patients and left sigmoid sinus in 19 patients. Absence of transverse sinus on left side was observed in one patient and absence of sigmoid sinus in 2 patients on left side. Flow gaps were observed in non-dominant transverse sinus, sigmoid sinus as well as transverse sigmoid sinus junctions. The occipital sinus was visualized in 17 patients., Conclusions: MR angiography done at low field strengths is also a reliable method, for assessing cerebral venous sinuses. Awareness of the normal anatomical variations of venous sinuses and apparent MR angiographic flow gaps prevent misdiagnosis of cerebral venous sinus thrombosis.

A micturating cystourethrography (MCU) examination is a specific radiological procedure that is performed under fluoroscopic screening to visualize the bladder by filling it with contrast material and to evaluate the urethral morphology during voiding. It is necessary to evaluate radiation dose during MCU examination since it involves radiosensitive organs such as the gonads. Radiation dose imparted to 109 patients undergoing MCU examination were measured using a dose-area product (DAP) meter. Patients were categorized into two groups based on whether filling of the bladder with contrast medium was done retrogradely (MCU) or by the suprapubic percutaneous route (SP-MCU). The DAP values to Group A (MCU) and Group B (SP-MCU) patients varied from 0.43 Gycm(2) to 9.26 Gycm(2) and 0.54 Gycm(2) to 9.87 Gycm(2), respectively. Reduction of radiation dose to patients was possible by the use of optimized exposure factors, precise collimation of X-ray beam, use of 0.2 mm copper filters and by acquiring images digitally.

Apligraf consists of bovine collagen dermis seeded with allogeneic male fibroblasts and keratinocytes. It is been shown to promote healing, but the length of persistence and pathological features have not been characterized previously in acute wounds. Forty-eight deep dermal wounds were created and Apligraf, a split-skin graft (SSG), or a dressing was applied. Biopsies of wounds were taken for immunohistochemical analysis and polymerase chain reaction was performed to detect the Y chromosome from Apligraf cells in 14 female wounds. Male allogeneic DNA was detected in wounds for the first 4 weeks. All subsequent time points were negative apart from one biopsy at 6 weeks. The wounds took 4-9 weeks to heal, with the Apligraf exhibiting no features of engraftment. This was in contrast to the rapid healing seen in the SSG control group. Histology revealed a more intense cellular infiltrate, but less vascularization below Apligraf compared with controls. Evidence of an epidermal-mesenchymal interaction was observed. This is the first article to elucidate the survival of Apligraf allogeneic cells in acute wounds in immunocompetent human subjects for up to 6 weeks and demonstrates that in the management of acute surgical wounds, Apligraf has a role only as a temporary biological dressing.

The radiation dose to voluntary kidney donors undergoing renal angiography performed using digital subtraction angiography (DSA) was estimated. The effective dose was calculated from values of dose-area product measured using a Diamentor dose-area product meter. The duration of the fluoroscopic screening and the number of image acquisitions during each examination varied depending upon the number of arteries supplying the kidneys and other parameters. The effective dose varied from 2.3 mSv to 30.5 mSv. The clinical aspects involved during the study were also taken into consideration in the analysis of the data.

Despite reduced fertility, pregnancy is likely to occur with increasing frequency in cystic fibrosis in proportion to the number of patients reaching childbearing age. Thirty-eight pregnancies in 25 patients with cystic fibrosis are presented. Twelve of the 25 mothers were pancreatic-sufficient. Despite previous reports of the hazards of pregnancy in cystic fibrosis, we found that pregnancy was well tolerated by the vast majority of our patients and had little effect on their pulmonary and nutritional status. Therapeutic abortion for medical indications was required in two pregnancies. The incidence of prematurity and the neonatal mortality rate were low, and no congenital abnormalities occurred. We conclude that pregnancy can be tolerated by the majority of cystic fibrosis patients, particularly those who are pancreatic-sufficient.