A Morphological Assessment of Bovine Chondrocytes Cultured on Poly(Ethyl Methacrylate)/Tetrahydrofurfuryl Methacrylate

A heterocyclic methacrylate polymer system, PEMA/THFMA, has shown potential as a biomaterial for cartilage repair in a rabbit model and has properties making it suitable for use clinically. The ability of the polymer system, PEMA/THFMA, and a related system, PEMA/HEMA, to support chondrocytes in vitro was assessed by scanning electron microscopy. Chondrocytes adhered to the surface of the PEMA/THFMA by day one, having a rounded morphology and clustered appearance opposed to the Thermanox® control, where the cells had spread out and become fibroblastic in appearance. The chondrocytes divided rapidly on the PEMA/ THFMA system by day three and had completely covered the surface by day seven. In contrast, chondrocytes did not adhere well to the more hydrophilic PEMA/ HEMA system. A few cells were seen on the surface by day one and by days three and seven, there was no evidence of cell growth or spreading across the surface. In conclusion, the PEMA/THFMA system can support chondrocytes in vitro, whereas the PEMA/HEMA system does not

Implementing a structured education program for children with diabetes: lessons learnt from an integrated process evaluation

There is recognition of an urgent need for clinic-based interventions for young people with type 1 diabetes mellitus that improve glycemic control and quality of life. The Child and Adolescent Structured Competencies Approach to Diabetes Education (CASCADE) is a structured educational group program, using psychological techniques, delivered primarily by diabetes nurses. Composed of four modules, it is designed for children with poor diabetic control and their parents. A mixed methods process evaluation, embedded within a cluster randomized control trial, aimed to assess the feasibility, acceptability, fidelity, and perceived impact of CASCADE

The blinking spotlight of attention

Increasing evidence suggests that attention can concurrently select multiple locations; yet it is not clear whether this ability relies on continuous allocation of attention to the different targets (a "parallel" strategy) or whether attention switches rapidly between the targets (a periodic "sampling" strategy). Here, we propose a method to distinguish between these two alternatives. The human psychometric function for detection of a single target as a function of its duration can be used to predict the corresponding function for two or more attended targets. Importantly, the predicted curves differ, depending on whether a parallel or sampling strategy is assumed. For a challenging detection task, we found that human performance was best reflected by a sampling model, indicating that multiple items of interest were processed in series at a rate of approximately seven items per second. Surprisingly, the data suggested that attention operated in this periodic regime, even when it was focused on a single target. That is, attention might rely on an intrinsically periodic process

Effectiveness of a structured educational intervention using psychological delivery methods in children and adolescents with poorly controlled type 1 diabetes: a cluster randomised controlled trial of the CASCADE intervention

Introduction: Type 1 diabetes in children and adolescents is increasing worldwide with a particular increase in children < 5 years. Fewer than one in six children and adolescents achieve recommended HbA1c values. Methods: A pragmatic, cluster randomised control trial assessed the efficacy of a clinic-based structured educational group incorporating psychological approaches to improve long-term glycaemic control, quality of life and psychosocial functioning in children and adolescents with T1D. 28 paediatric diabetes services were randomised to deliver the intervention or standard care. 362 children (8-16 years) HbA1c ≥ 8.5% were recruited. Outcomes were HbA1c at 12 and 24 months, hypoglycaemia, admissions, self-management skills, intervention compliance, emotional and behavioural adjustment and quality of life. A process evaluation collected data from key stakeholder groups in order to evaluate the feasibility of delivering the intervention. Results: 298/362 patients (82.3%) provided HbA1c at 12 months and 284/362 (78.5%) at 24 months. The intervention did not improve HbA1c at 12 months (intervention effect 0.11, 95% CI −0.28 to 0.50, P=0.584), or 24 months (intervention effect 0.03, 95% CI -0.36 to 0.41, P=0.891). There were no significant changes in remaining outcomes. 96/180 (53%) families in the intervention arm attended at least one module. The number of modules attended did not affect outcome. Reasons for low uptake included difficulties organising groups and work and school commitments. Those with highest HbA1cs were less likely to attend. Mean cost of the intervention was £683 per child. Conclusions: Significant challenges in the delivery of a structured education intervention using psychological techniques to enhance engagement and behaviour change delivered by diabetes nurses and dietitians in routine clinical practice were found. The intervention did not improve HbA1c in children and adolescents with poor control

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

A Zebrafish Compound Screen Reveals Modulation of Neutrophil Reverse Migration as an Anti-Inflammatory Mechanism

Diseases of failed inflammation resolution are common and largely incurable. Therapeutic induction of inflammation resolution is an attractive strategy to bring about healing without increasing susceptibility to infection. However, therapeutic targeting of inflammation resolution has been hampered by a lack of understanding of the underlying molecular controls. To address this drug development challenge, we developed an in vivo screen for proresolution therapeutics in a transgenic zebrafish model. Inflammation induced by sterile tissue injury was assessed for accelerated resolution in the presence of a library of known compounds. Of the molecules with proresolution activity, tanshinone IIA, derived from a Chinese medicinal herb, potently induced inflammation resolution in vivo both by induction of neutrophil apoptosis and by promoting reverse migration of neutrophils. Tanshinone IIA blocked proinflammatory signals in vivo, and its effects are conserved in human neutrophils, supporting a potential role in treating human inflammation and providing compelling evidence of the translational potential of this screening strategy

Group antenatal care: findings from a pilot randomised controlled trial of REACH Pregnancy Circles

BACKGROUND: Antenatal care has the potential to impact positively on maternal and child outcomes, but traditional models of care in the UK have been shown to have limitations and particularly for those from deprived populations. Group antenatal care is an alternative model to traditional individual care. It combines conventional aspects of antenatal assessment with group discussion and support. Delivery of group antenatal care has been shown to be successful in various countries; there is now a need for a formal trial in the UK. METHOD: An individual randomised controlled trial (RCT) of a model of group care (Pregnancy Circles) delivered in NHS settings serving populations with high levels of deprivation and diversity was conducted in an inner London NHS trust. This was an external pilot study for a potential fully powered RCT with integral economic evaluation. The pilot aimed to explore the feasibility of methods for the full trial. Inclusion criteria included pregnant with a due date in a certain range, 16 + years and living within specified geographic areas. Data were analysed for completeness and usability in a full trial; no hypothesis testing for between-group differences in outcome measures was undertaken. Pre-specified progression criteria corresponding to five feasibility measures were set. Additional aims were to assess the utility of our proposed outcome measures and different data collection routes. A process evaluation utilising interviews and observations was conducted. RESULTS: Seventy-four participants were randomised, two more than the a priori target. Three Pregnancy Circles of eight sessions each were run. Interviews were undertaken with ten pregnant participants, seven midwives and four other stakeholders; two observations of intervention sessions were conducted. Progression criteria were met at sufficient levels for all five measures: available recruitment numbers, recruitment rate, intervention uptake and retention and questionnaire completion rates. Outcome measure assessments showed feasibility and sufficient completion rates; the development of an economic evaluation composite measure of a 'positive healthy birth' was initiated. CONCLUSION: Our pilot findings indicate that a full RCT would be feasible to conduct with a few adjustments related to recruitment processes, language support, accessibility of intervention premises and outcome assessment. TRIAL REGISTRATION: ISRCTN ISRCTN66925258. Retrospectively registered, 03 April 2017

Grain refinement of Al-Mg-Sc alloy by ultrasonic treatment

In foundry practice, ultrasonic treatment has been used as an efficient technique to achieve grain refinement in aluminium and magnesium alloys. This article shows the strong effect of pouring temperature and ultrasonic treatment at various temperatures on the grain refinement of Al-1 wt% Mg-0.3 wt% Sc alloy. Without ultrasonic treatment, a fine grain structure was obtained at the pouring temperature of 700 °C. The average grain size sharply decreases from 487 ± 20 to 103 ± 2 μm when the pouring temperature decreases from 800 to 700 °C. Ultrasonic vibration proved to be a potential grain refinement technique with a wide range of pouring tem- perature. A microstructure with very fine and homogeneous grains was obtained by applying ultrasonic treatment to the melt at the temperature range between 700 and 740 °C, before pouring. Cavitation-enhanced hetero- geneous nucleation is the mechanism proposed to explain grain refinement by ultrasound in this alloy. Moreover, ultrasonic treatment of the melt was found to lead to cast samples with hardness values similar to those obtained in samples submitted to precipitation hardening, suggesting that ultrasonic treatment can avoid carrying out heat treatment of cast parts.This research was supported by The Project Bridging The Gap, funded by the Erasmus Mundus External Cooperation Window Programme. Acknowledgements also to the University of Minho, for the provision of research facilities

Group antenatal care (Pregnancy Circles) for diverse and disadvantaged women: study protocol for a randomised controlled trial with integral process and economic evaluations

Background Group antenatal care has been successfully implemented around the world with suggestions of improved outcomes, including for disadvantaged groups, but it has not been formally tested in the UK in the context of the NHS. To address this the REACH Pregnancy Circles intervention was developed and a randomised controlled trial (RCT), based on a pilot study, is in progress. Methods The RCT is a pragmatic, two-arm, individually randomised, parallel group RCT designed to test clinical and cost-effectiveness of REACH Pregnancy Circles compared with standard care. Recruitment will be through NHS services. The sample size is 1732 (866 randomised to the intervention and 866 to standard care). The primary outcome measure is a ‘healthy baby’ composite measured at 1 month postnatal using routine maternity data. Secondary outcome measures will be assessed using participant questionnaires completed at recruitment (baseline), 35 weeks gestation (follow-up 1) and 3 months postnatal (follow-up 2). An integrated process evaluation, to include exploration of fidelity, will be conducted using mixed methods. Analyses will be on an intention to treat as allocated basis. The primary analysis will compare the number of babies born “healthy” in the control and intervention arms and provide an odds ratio. A cost-effectiveness analysis will compare the incremental cost per Quality Adjusted Life Years and per additional ‘healthy and positive birth’ of the intervention with standard care. Qualitative data will be analysed thematically. Discussion This multi-site randomised trial in England is planned to be the largest trial of group antenatal care in the world to date; as well as the first rigorous test within the NHS of this maternity service change. It has a recruitment focus on ethnically, culturally and linguistically diverse and disadvantaged participants, including non-English speakers. Trial registration Trial registration; ISRCTN, ISRCTN91977441. Registered 11 February 2019 - retrospectively registered. The current protocol is Version 4; 28/01/2020

A physical activity intervention for children with type 1 diabetes- steps to active kids with diabetes (STAK-D): a feasibility study

Background This study describes the development and feasibility evaluation of a physical activity intervention for children with type 1 diabetes called ‘Steps to Active Kids with Diabetes’ (STAK-D). It aims to explore the feasibility and acceptability of the intervention and study design. Methods Thirteen children aged 9-11 years and their parents were recruited from one paediatric diabetes clinic. A process evaluation was conducted alongside a two-arm randomised feasibility trial, including assessment of rate of recruitment, adherence, retention, data completion and burden, implementation fidelity and adverse events. Qualitative interviews with children (n=9), parents (n=8), healthcare professionals (n=3) and STAK-D volunteers (n=8) explored intervention acceptability. Interviews were analysed thematically. Results Rate of recruitment was 25%, with 77% retention at 3-month follow-up. Study burden was low, data completion was high and the intervention was delivered as per protocol. No serious adverse event was reported. Engagement with intervention materials was generally good, but attendance at group activity sessions was low due to logistical barriers. Interview analysis identified preferred methods of recruitment, motivations for recruitment, barriers and facilitators to adherence, the experience of data collection, experience of the STAK-D programme and its perceived benefits. Conclusions STAK-D was feasible and acceptable to children, their parents and healthcare professionals, but group sessions may present logistical issues. Recruitment and retention may be improved with a clinic-wide approach to recruitment. Trial registration This trial was registered on ClinicalTrials.gov: NCT02144337 (16/01/2014). Keywords Children, feasibility study, intervention, paediatric diabetes, physical activity, process evaluation, self-efficacy, type 1 diabete