The use of equine chondrogenic‐induced mesenchymal stem cells as a treatment for osteoarthritis : a randomised, double‐blinded, placebo‐controlled proof‐of‐concept study

Background: There is a need to improve therapies for osteoarthritis in horses. Objectives To assess the efficacy of equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses. Study design: Randomised, double-blinded, placebo-controlled experiment. Methods: In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment-groove model. Five weeks after surgery, horses were randomly assigned to either an intra-articular injection with chondrogenic-induced mesenchymal stem cells + equine allogeneic plasma (= intervention) or with 0.9% saline solution (= control). From surgery until the study end, horses underwent a weekly joint and lameness assessment. Synovial fluid was collected for cytology and biomarker analysis before surgery and at Weeks 5, 5 + 1d, 7, 9 and 11. At Week 11, horses were subjected to euthanasia, and the metacarpophalangeal joints were evaluated macroscopically and histologically. Results: No serious adverse events or suspected adverse drug reactions occurred during the study. A significant improvement in visual and objective lameness was seen with the intervention compared with the control. Synovial fluid displayed a significantly higher viscosity and a significantly lower glycosaminoglycan concentration in the intervention group. Other biomarkers or cytology parameters were not significantly different between the treatment groups. Significantly less wear lines and synovial hyperaemia were present in the intervention group. The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans were significantly higher in the articular cartilage of the intervention group. Main limitations: This study assessed the short-term effect of the intervention on a limited number of horses, using an osteoarthritis model. This study also included multiple statistical tests, increasing the risk of type 1 error. Conclusions: Equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma may be a promising treatment for osteoarthritis in horses

Experience of unpleasant sensations in the mouth after injection of saline from prefilled syringes

Background Nurses at The Norwegian Radium Hospital have reported that some patients notice an unpleasant smell or taste in accordance with flushing of intravenous lines with commercially available prefilled syringes. We have conducted a study in healthy volunteers to investigate the occurrence, consistency and intensity of this phenomenon. Methods A randomised, blinded, crossover study comparing commercial available prefilled saline 9 mg/ml syringes to saline 9 mg/ml for injection in polyethylene package was performed in 10 healthy volunteers. The volunteers were given intravenous injections of varying volume and speed. Data were analysed using descriptive statistics, and also Wilcoxon Signed Rank Test to compare groups. Results After intravenous injection, 2 of 15 recordings demonstrated any sensation of smell or taste after injection of saline from polyethylene package, while 14 of 15 recordings noted a sensation after injection of saline from prefilled syringes. The intensity of the unpleasant sensation was rated significantly higher after injection of saline from prefilled syringes compared to saline from polyethylene (p = 0.001). Conclusions Injection of saline from prefilled syringes in healthy volunteers resulted in an experience of bad taste or smell. It is important that nurses and health workers are aware of the phenomenon as described in this article in order to choose the preferred product for a given patient

Effectiveness of food supplements in increasing fat-free tissue accretion in children with moderate acute malnutrition: A randomised 2 × 2 × 3 factorial trial in Burkina Faso.

BACKGROUND: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplement (LNS) or corn-soy blend (CSB). We assessed the effectiveness of (a) matrix, i.e., LNS or CSB, (b) soy quality, i.e., soy isolate (SI) or dehulled soy (DS), and (c) percentage of total protein from dry skimmed milk, i.e., 0%, 20%, or 50%, in increasing fat-free tissue accretion. METHODS AND FINDINGS: Between September 9, 2013, and August 29, 2014, a randomised 2 × 2 × 3 factorial trial recruited 6- to 23-month-old children with MAM in Burkina Faso. The intervention comprised 12 weeks of food supplementation providing 500 kcal/day as LNS or CSB, each containing SI or DS, and 0%, 20%, or 50% of protein from milk. Fat-free mass (FFM) was assessed by deuterium dilution technique. By dividing FFM by length squared, the primary outcome was expressed independent of length as FFM index (FFMI) accretion over 12 weeks. Other outcomes comprised recovery rate and additional anthropometric measures. Of 1,609 children, 4 died, 61 were lost to follow-up, and 119 were transferred out due to supplementation being switched to non-experimental products. No children developed allergic reaction. At inclusion, 95% were breastfed, mean (SD) weight was 6.91 kg (0.93), with 83.5% (5.5) FFM. In the whole cohort, weight increased 0.90 kg (95% CI 0.88, 0.93; p 0.05). LNS compared to CSB resulted in 128 g (95% CI 67, 190; p < 0.01) greater weight gain if both contained SI, but there was no difference between LNS and CSB if both contained DS (mean difference 22 g; 95% CI -40, 84; p = 0.49) (interaction p = 0.017). Accordingly, SI compared to DS increased weight by 89 g (95% CI 27, 150; p = 0.005) when combined with LNS, but not when combined with CSB. A limitation of this and other food supplementation trials is that it is not possible to collect reliable data on individual adherence. CONCLUSIONS: Based on this study, children with MAM mainly gain fat-free tissue when rehabilitated. Nevertheless, LNS yields more fat-free tissue and higher recovery rates than CSB. Moreover, current LNSs with DS may be improved by shifting to SI. The role of milk relative to soy merits further research. TRIAL REGISTRATION: ISRCTN registry ISRCTN42569496

Sensory Measurements: Coordination and Standardization

Do sensory measurements deserve the label of “measurement”? We argue that they do. They fit with an epistemological view of measurement held in current philosophy of science, and they face the same kinds of epistemological challenges as physical measurements do: the problem of coordination and the problem of standardization. These problems are addressed through the process of “epistemic iteration,” for all measurements. We also argue for distinguishing the problem of standardization from the problem of coordination. To exemplify our claims, we draw on olfactory performance tests, especially studies linking olfactory decline to neurodegenerative disorders

Translation of evidence-based Assistive Technologies into stroke rehabilitation: Users' perceptions of the barriers and opportunities

Background: Assistive Technologies (ATs), defined as "electrical or mechanical devices designed to help people recover movement", demonstrate clinical benefits in upper limb stroke rehabilitation; however translation into clinical practice is poor. Uptake is dependent on a complex relationship between all stakeholders. Our aim was to understand patients', carers' (P&Cs) and healthcare professionals' (HCPs) experience and views of upper limb rehabilitation and ATs, to identify barriers and opportunities critical to the effective translation of ATs into clinical practice. This work was conducted in the UK, which has a state funded healthcare system, but the findings have relevance to all healthcare systems. Methods. Two structurally comparable questionnaires, one for P&Cs and one for HCPs, were designed, piloted and completed anonymously. Wide distribution of the questionnaires provided data from HCPs with experience of stroke rehabilitation and P&Cs who had experience of stroke. Questionnaires were designed based on themes identified from four focus groups held with HCPs and P&Cs and piloted with a sample of HCPs (N = 24) and P&Cs (N = 8). Eight of whom (four HCPs and four P&Cs) had been involved in the development. Results: 292 HCPs and 123 P&Cs questionnaires were analysed. 120 (41%) of HCP and 79 (64%) of P&C respondents had never used ATs. Most views were common to both groups, citing lack of information and access to ATs as the main reasons for not using them. Both HCPs (N = 53 [34%]) and P&C (N = 21 [47%]) cited Functional Electrical Stimulation (FES) as the most frequently used AT. Research evidence was rated by HCPs as the most important factor in the design of an ideal technology, yet ATs they used or prescribed were not supported by research evidence. P&Cs rated ease of set-up and comfort more highly. Conclusion: Key barriers to translation of ATs into clinical practice are lack of knowledge, education, awareness and access. Perceptions about arm rehabilitation post-stroke are similar between HCPs and P&Cs. Based on our findings, improvements in AT design, pragmatic clinical evaluation, better knowledge and awareness and improvement in provision of services will contribute to better and cost-effective upper limb stroke rehabilitation. © 2014 Hughes et al.; licensee BioMed Central Ltd

Improving the efficiency of clinical trials in multiple sclerosis

BACKGROUND: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. OBJECTIVE: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. METHODS: We held an international workshop with experts in clinical trial design. RESULTS: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. CONCLUSION: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions

Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work

Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis

: EPHPP quality rating scores (DOCX 38 kb

Ambient-aware continuous care through semantic context dissemination

Background: The ultimate ambient-intelligent care room contains numerous sensors and devices to monitor the patient, sense and adjust the environment and support the staff. This sensor-based approach results in a large amount of data, which can be processed by current and future applications, e. g., task management and alerting systems. Today, nurses are responsible for coordinating all these applications and supplied information, which reduces the added value and slows down the adoption rate. The aim of the presented research is the design of a pervasive and scalable framework that is able to optimize continuous care processes by intelligently reasoning on the large amount of heterogeneous care data. Methods: The developed Ontology-based Care Platform (OCarePlatform) consists of modular components that perform a specific reasoning task. Consequently, they can easily be replicated and distributed. Complex reasoning is achieved by combining the results of different components. To ensure that the components only receive information, which is of interest to them at that time, they are able to dynamically generate and register filter rules with a Semantic Communication Bus (SCB). This SCB semantically filters all the heterogeneous care data according to the registered rules by using a continuous care ontology. The SCB can be distributed and a cache can be employed to ensure scalability. Results: A prototype implementation is presented consisting of a new-generation nurse call system supported by a localization and a home automation component. The amount of data that is filtered and the performance of the SCB are evaluated by testing the prototype in a living lab. The delay introduced by processing the filter rules is negligible when 10 or fewer rules are registered. Conclusions: The OCarePlatform allows disseminating relevant care data for the different applications and additionally supports composing complex applications from a set of smaller independent components. This way, the platform significantly reduces the amount of information that needs to be processed by the nurses. The delay resulting from processing the filter rules is linear in the amount of rules. Distributed deployment of the SCB and using a cache allows further improvement of these performance results

Influences of the G2350A polymorphism in the ACE Gene on cardiac structure and function of ball game players

<p>Abstract</p> <p>Background</p> <p>Except for the I/D polymorphism in the angiotensin I-converting enzyme (ACE) gene, there were few reports about the relationship between other genetic polymorphisms in this gene and the changes in cardiac structure and function of athletes. Thus, we investigated whether the G2350A polymorphism in the <it>ACE </it>gene is associated with the changes in cardiac structure and function of ball game players. Total 85 healthy ball game players were recruited in this study, and they were composed of 35 controls and 50 ball game players, respectively. Cardiac structure and function were measured by 2-D echocardiography, and the G2350A polymorphism in the <it>ACE </it>gene analyzed by the SNaPshot method.</p> <p>Results</p> <p>There were significant differences in left ventricular mass index (LVmassI) value among each sporting discipline studied. Especially in the athletes of basketball disciplines, indicated the highest LVmassI value than those of other sporting disciplines studied (p < 0.05). However, there were no significant association between any echocardiographic data and the G2350A polymorphism in the <it>ACE </it>gene in the both controls and ball game players.</p> <p>Conclusions</p> <p>Our data suggests that the G2350A polymorphism in the <it>ACE </it>gene may not significantly contribute to the changes in cardiac structure and function of ball game players, although sporting disciplines of ball game players may influence the changes in LVmassI value of these athletes. Further studies using a larger sample size and other genetic markers in the <it>ACE </it>gene will be needed.</p