Attenuated Semliki Forest virus for cancer treatment in dogs : safety assessment in two laboratory Beagles

Background: Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of similar to 2 x 10(5) plaque forming units of parental A7(74) strain. Results: VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination. Conclusions: Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.Peer reviewe

Cardiorespiratory fitness is associated with sickness absence and work ability

BACKGROUND: Physical activity may sustain the physical aspect of work ability despite health problems such as musculoskeletal disorders and anxiety, which are the most prevalent work-related health problem in Europe. AIMS: To evaluate the association of Finnish municipal workers' accelerometer-measured physical activity, sedentary behaviour, and cardiorespiratory and muscular fitness with their sickness absence levels, perceived work ability and health-related quality of life. METHODS: In connection with a randomized controlled trial recruiting 185 municipal workers, the authors performed baseline data analysis utilizing quantile regression to examine relationships between the outcome variables (all-cause sickness absence for 6 months, perceived work ability and health-related quality of life) and cardiorespiratory fitness, muscular fitness, and physical activity, and sedentary behaviour. All results were adjusted for age, sex and education level. RESULTS: The median duration of all-cause sickness absence over the preceding 6 months was lowest among participants with high cardiorespiratory fitness relative to the lowest tertile (2.0 versus 6.0 days; P < 0.05), and the highest perceived work ability was found among those with high or moderate cardiorespiratory fitness as compared to the lowest tertile (8.0 versus 7.0; P < 0.001). Moderate-to-vigorous physical activity correlated positively with the physical component of health-related quality of life (P < 0.01) and with a high cardiorespiratory-fitness level (P < 0.05). CONCLUSIONS: High cardiorespiratory fitness was associated with decreased all-cause sickness absence days and improved work ability among municipal workers.publishedVersionPeer reviewe

Personalised eHealth intervention to increase physical activity and reduce sedentary behaviour in rehabilitation after cardiac operations: Study protocol for the PACO randomised controlled trial (NCT03470246)

Introduction: Personalized intervention to increase physical Activity and reduce sedentary behaviour in rehabilitation after Cardiac Operations (PACO) is a smartphone-based and accelerometer-based eHealth intervention to increase physical activity (PA) and reduce sedentary behaviour (SB) among patients recovering from cardiac surgery.Design: Prospective randomised controlled trial.Methods and analysis: The present protocol describes a randomised controlled clinical trial to be conducted in the Heart Centres of Kuopio and Turku university hospitals. The trial comprises 540 patients scheduled for elective coronary artery bypass grafting, aortic valve replacement or mitral valve repair. The patients will be randomised into two groups. The control group will receive standard postsurgical rehabilitation guidance. The eHealth intervention group will be given the same guidance together with personalised PA guidance during 90 days after discharge. These patients will receive personalised daily goals to increase PA and reduce SB via the ExSedapplication. Triaxial accelerometers will be exploited to record patients’ daily accumulated PA and SB, and transmit them to the application. Using the accelerometer data, the application will provide online guidance to the patients and feedback of accomplishing their activity goals. The data will also be transmitted to the cloud, where a physiotherapist can monitor individual activity profiles and customise the subsequent PA and SB goals online. The postoperative improvement in patients’ step count, PA, exercise capacity, quality of sleep, laboratory markers, transthoracic echocardiography (TTE) parameters and quality of life, and reduction in SB and incidence of major cardiac events are investigated as outcomes.Conclusions: The PACO intervention aims to build a personalised eHealth tool for the online tutoring of cardiac surgery patients.</p

Cross-species amplification of 41 microsatellites in European cyprinids: A tool for evolutionary, population genetics and hybridization studies

<p>Abstract</p> <p>Background</p> <p>Cyprinids display the most abundant and widespread species among the European freshwater Teleostei and are known to hybridize quite commonly. Nevertheless, a limited number of markers for conducting comparative differentiation, evolutionary and hybridization dynamics studies are available to date.</p> <p>Findings</p> <p>Five multiplex PCR sets were optimized in order to assay 41 cyprinid-specific polymorphic microsatellite loci (including 10 novel loci isolated from <it>Chondrostoma nasus nasus, Chondrostoma toxostoma toxostoma </it>and <it>Leuciscus leuciscus</it>) for 503 individuals (440 purebred specimens and 63 hybrids) from 15 European cyprinid species. The level of genetic diversity was assessed in <it>Alburnus alburnus, Alburnoides bipunctatus, C. genei, C. n. nasus, C. soetta, C. t. toxostoma, L. idus, L. leuciscus, Pachychilon pictum, Rutilus rutilus, Squalius cephalus </it>and <it>Telestes souffia</it>. The applicability of the markers was also tested on <it>Abramis brama, Blicca bjoerkna </it>and <it>Scardinius erythrophtalmus </it>specimens. Overall, between 24 and 37 of these markers revealed polymorphic for the investigated species and 23 markers amplified for all the 15 European cyprinid species.</p> <p>Conclusions</p> <p>The developed set of markers demonstrated its performance in discriminating European cyprinid species. Furthermore, it allowed detecting and characterizing hybrid individuals. These microsatellites will therefore be useful to perform comparative evolutionary and population genetics studies dealing with European cyprinids, what is of particular interest in conservation issues and constitutes a tool of choice to conduct hybridization studies.</p

Physical activity measured by accelerometry among adolescents participating in sports clubs and non-participating peers

The purpose of this descriptive cross-sectional study is to describe the amount and intensity of physical activity (PA) measured by accelerometry among adolescents participating in organized sports (SCP) and age-matched non-participating peers (NP). SCPs (332) and NPs (139) wore an accelerometer on the hip for seven days. PA was reported using the 1-min exponential moving average. The current moderate-to-vigorous physical activity (MVPA) recommendation of at least an average of 60 min of MVPA daily was reached by 85% of SCPs and 45% of NPs (p < .001). During training days, the MVPA times among SCPs ranged from 153 ± 39 min in males and 109 ± 35 min in females participating in basketball to 113 ± 33 min in males participating in floorball and 83 ± 32 min in females participating in gymnastics. Sports participation contributes rather strongly to the accumulation of the recommended amount of MVPA. During training days, SCPs, except for females participating in gymnastics, accumulated more MVPA than NPs. During non-training days, only males participating in cross-country skiing and females participating in track and field accumulated more MVPA than NPs. HIGHLIGHTSPA of Finnish adolescents participating in nine different organized sports and age-matched non-participating peers was measured by accelerometry for one week and the results are reported using the 1-min exponential moving average.Adolescents participating in many organized sports accumulated more PA than non-participants; this was observed in meeting the PA recommendations, total amount of PA at different intensities, and step count.The current PA recommendation of at least an average of 60 min of MVPA per day was reached by 85% of SCPs and 45% of non-participating peers. Vigorous physical activity at least three times per week was incorporated by 96% of SCPs and 81% of NPs.During training days, males participating in soccer, basketball, and cross-country skiing spent more time in MVPA than females participating in the same sports. During non-training days, the time spent in MVPA was similar between males and females participating in sports clubs.publishedVersionPeer reviewe

Physical activity measured by accelerometry among adolescents participating in sports clubs and non-participating peers

The purpose of this descriptive cross-sectional study is to describe the amount and intensity of physical activity (PA) measured by accelerometry among adolescents participating in organized sports (SCP) and age-matched non-participating peers (NP). SCPs (332) and NPs (139) wore an accelerometer on the hip for seven days. PA was reported using the 1-min exponential moving average. The current moderate-to-vigorous physical activity (MVPA) recommendation of at least an average of 60 min of MVPA daily was reached by 85% of SCPs and 45% of NPs (p PA of Finnish adolescents participating in nine different organized sports and age-matched non-participating peers was measured by accelerometry for one week and the results are reported using the 1-min exponential moving average.Adolescents participating in many organized sports accumulated more PA than non-participants; this was observed in meeting the PA recommendations, total amount of PA at different intensities, and step count.The current PA recommendation of at least an average of 60 min of MVPA per day was reached by 85% of SCPs and 45% of non-participating peers. Vigorous physical activity at least three times per week was incorporated by 96% of SCPs and 81% of NPs. During training days, males participating in soccer, basketball, and cross-country skiing spent more time in MVPA than females participating in the same sports. During non-training days, the time spent in MVPA was similar between males and females participating in sports clubs.</ul

A review of friction models in interacting joints for durability design.

This paper presents a comprehensive review of friction modelling to provide an understanding of design for durability within interacting systems. Friction is a complex phenomenon and occurs at the interface of two components in relative motion. Over the last several decades, the effects of friction and its modelling techniques have been of significant interests in terms of industrial applications. There is however a need to develop a unified mathematical model for friction to inform design for durability within the context of varying operational conditions. Classical dynamic mechanisms model for the design of control systems has not incorporated friction phenomena due to non-linearity behaviour. Therefore, the tribological performance concurrently with the joint dynamics of a manipulator joint applied in hazardous environments needs to be fully analysed. Previously the dynamics and impact models used in mechanical joints with clearance have also been examined. The inclusion of reliability and durability during the design phase is very important for manipulators which are deployed in harsh environmental and operational conditions. The revolute joint is susceptible to failures such as in heavy manipulators these revolute joints can be represented by lubricated conformal sliding surfaces. The presence of pollutants such as debris and corrosive constituents has the potential to alter the contacting surfaces, would in turn affect the performance of revolute joints, and puts both reliability and durability of the systems at greater risks of failure. Key literature is identified and a review on the latest developments of the science of friction modelling is presented here. This review is based on a large volume of knowledge. Gaps in the relevant field have been identified to capitalise on for future developments. Therefore, this review will bring significant benefits to researchers, academics and industrial professionals

Drug Target Commons : A Community Effort to Build a Consensus Knowledge Base for Drug-Target Interactions

Knowledge of the full target space of bioactive substances, approved and investigational drugs as well as chemical probes, provides important insights into therapeutic potential and possible adverse effects. The existing compound-target bioactivity data resources are often incomparable due to non-standardized and heterogeneous assay types and variability in endpoint measurements. To extract higher value from the existing and future compound target-profiling data, we implemented an open-data web platform, named Drug Target Commons (DTC), which features tools for crowd-sourced compound-target bioactivity data annotation, standardization, curation, and intra-resource integration. We demonstrate the unique value of DTC with several examples related to both drug discovery and drug repurposing applications and invite researchers to join this community effort to increase the reuse and extension of compound bioactivity data.Peer reviewe

Hybridization but No Evidence for Backcrossing and Introgression in a Sympatric Population of Great Reed Warblers and Clamorous Reed Warblers

Hybridization is observed frequently in birds, but often it is not known whether the hybrids are fertile and if backcrossing occurs. The breeding ranges of the great reed warbler (Acrocephalus arundinaceus) and the clamorous reed warbler (A. stentoreus) overlap in southern Kazakhstan and a previous study has documented hybridization in a sympatric population. In the present study, we first present a large set of novel microsatellite loci isolated and characterised in great reed warblers. Secondly, we evaluate whether hybridization in the sympatric breeding population has been followed by backcrossing and introgression