The anti-inflammatory effects of equine bone marrow stem cell-derived extracellular vesicles on autologous chondrocytes.

Funder: BBSRC BrightStar StudentshipBACKGROUND: Osteoarthritis (OA) in the horse is an economic and welfare issue and there are no current disease modifying drugs available. Stem cells have been suggested as a therapeutic intervention for OA, originally on the basis of their regenerative capacity. However, it is hypothesised that mesenchymal stem cells (MSC) exert their effects via paracrine factors including the production of extracellular vesicles that can themselves recapitulate the MSC effects in the joint. OBJECTIVES: To isolate extracellular vesicles from bone marrow MSC and investigate their anti-inflammatory effects on chondrocytes. STUDY DESIGN: An in vitro assessment of the effect of direct culturing extracellular vesicles on artificially inflamed chondrocytes. METHODS: Extracellular vesicles were isolated from bone marrow MSC using differential sequential ultracentrifugation. Vesicles were characterised using electron microscopy, nanoparticle tracing analysis and protein analysis. Vesicle internalisation was carried out via vesicles being pre-stained and co-cultured with equine chondrocytes before analysis using confocal microscopy. The effects of vesicles on artificially inflamed chondrocytes was examined using quantitative PCR. RESULTS: To the best of the authors' knowledge, this is the first study to isolate and characterise extracellular vesicles from equine bone MSC. Vesicles were taken up by autologous chondrocytes and had anti-inflammatory effects on gene expression following chondrocyte exposure to tumour necrosis factor α and Interleukin 1β. MAIN LIMITATIONS: Only three independent biological repeats were performed and the work was done in vitro. CONCLUSION: Extracellular vesicles can be isolated from equine bone marrow MSC; they may be taken up by chondrocytes and have an anti-inflammatory action

Modelling the Reallocation of Time Spent Sitting into Physical Activity: Isotemporal Substitution vs. Compositional Isotemporal Substitution.

Isotemporal substitution modelling (ISM) and compositional isotemporal modelling (CISM) are statistical approaches used in epidemiology to model the associations of replacing time in one physical behaviour with time in another. This study's aim was to use both ISM and CISM to examine and compare associations of reallocating 60 min of sitting into standing or stepping with markers of cardiometabolic health. Cross-sectional data collected during three randomised control trials (RCTs) were utilised. All participants (n = 1554) were identified as being at high risk of developing type 2 diabetes. Reallocating 60 min from sitting to standing and to stepping was associated with a lower BMI, waist circumference, and triglycerides and higher high-density lipoprotein cholesterol using both ISM and CISM (p < 0.05). The direction and magnitude of significant associations were consistent across methods. No associations were observed for hemoglobin A1c, total cholesterol, or low-density lipoprotein cholesterol for either method. Results of both ISM and CISM were broadly similar, allowing for the interpretation of previous research, and should enable future research in order to make informed methodological, data-driven decisions

Associations of objectively measured moderate-to-vigorous-intensity physical activity and sedentary time with all-cause mortality in a population of adults at high risk of type 2 diabetes mellitus

The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge,we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010–2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality.MVPA and sedentary time were assessed by accelerometer; those with valid data (≥10 hours of wear-time/day with ≥4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p=0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p=0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation

Image processing using Android device - gas-meter value recognition

Diplomová práce se zabývá návrhem zpracování obrazu v systému Android. Volbou vývojového prostředí a jeho implementací. Pracovní postup řešení problematiky zahrnuje vytvoření aplikace a grafického uživatelského rozhraní. Text zahrnuje popis funkcionality aplikace, komunikace s fotoaparátem, uložení a načítání dat. Dále popisuje použité algoritmy a metody zpracování obrazu pro detekci hodnot plynoměru.This thesis describes the design of the image processing for Android system, consisting of the choice of the development environment and its implementation. Workflow solution to the problem involves development of the Androidapplication and it’s graphical user interface. The text includes description of the application functionality, communicationwith a camera, storing and retrieving data. It also describes used algorithms and image processing methods used for detecting values from the counter of the gas meter.

Fitness moderates glycemic responses to sitting and light activity breaks

Purpose: Regular engagement in sedentary behaviours can lead to major public health consequences. This study aimed to experimentally determine whether cardio-respiratory fitness modifies postprandial glycemia during prolonged sitting and investigated the potentially blunting influence this may have upon the benefits of interrupting postprandial sitting time with light activity breaks. Methods: Thirty–four adult volunteers (18female; 16male; mean±SD age: 40±9 years, BMI: 24.5±3 kg/m2) undertook two 7·5 hour experimental conditions in a randomized order: 1) Prolonged sitting; 2) Sitting interspersed with 5 minute light walking bouts every 30minutes. Blood samples were obtained while fasting and throughout the postprandial period following ingestion of two identical meals. Incremental Area Under the Curve (iAUC) was calculated for glucose and insulin throughout each experimental condition. Maximal exercise testing quantified VO2 peak as a measure of cardiorespiratory fitness (CRF) prior to experimental conditions. A repeated measures ANOVA investigated whether VO2 peak modified iAUC data between conditions. This trial is registered with ClinicalTrials.gov (Reg no.NCT0493309). Results: Interrupting prolonged sitting time with light walking breaks reduced blood glucose iAUC from 3.89 ± 0.7 to 2·51 ± 0.7 mmol·L-1·h (p = 0.015) and insulin iAUC from 241 ± 46 to 156 ± 24 mU·L-1·h (p = 0.013) after adjustment for VO2 peak and sex. A significant interaction between treatment response and VO2 peak was observed for glucose (p = 0.035), but not insulin (p = 0.062), whereby the treatment effect reduced with higher levels of fitness. Average blood glucose iAUC responses for a man at the 25th centile of CRF (42.5 mL∙kg-1∙min-1) within our cohort went from 5.80 to 2.98 mmol·L-1·h during the prolonged sitting and light walking breaks conditions respectively, whereas average responses for a man at the 75th centile of CRF (60.5 mL∙kg-1∙min-1) went from 1.99 to 1.78 mmol·L-1·h. Similar trends were observed for women. Conclusions: Individuals with low levels of CRF gained the most metabolic benefit from breaking prolonged sitting with regular bouts of light walking. Future interventions aimed at alleviating the deleterious impacts of sedentary behavior may be optimized by tailoring to cardio-respiratory fitness levels within the general population

Associations of objectively measured moderate-to-vigorous-intensity physical activity and sedentary time with all-cause mortality in a population of adults at high risk of type 2 diabetes mellitus

a b s t r a c t a r t i c l e i n f o The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge, we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010-2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality. MVPA and sedentary time were assessed by accelerometer; those with valid data (≥10 hours of wear-time/day with ≥4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p = 0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p = 0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation

activPAL and ActiGraph Assessed Sedentary Behavior and Cardiometabolic Health Markers

Purpose To establish whether associations between sedentary behavior and cardiometabolic health differ when assessed by thigh-worn and waist-worn accelerometry. Methods Participants were recruited from several areas in the United Kingdom. Sedentary behavior was assessed using the activPAL worn on the thigh and ActiGraph worn on the waist. Average total (TST), prolonged (bouts ≥30 min; PST) and breaks (BST) in sedentary time were calculated. Cardiometabolic health markers included: adiposity (body fat) and surrogate markers of adiposity ((waist circumference, body mass index [BMI]), lipids (total, low density lipoprotein, and high-density lipoprotein [HDL] cholesterol, triglycerides), blood pressure, and glucose (fasting, 2 h and glycated hemoglobin A1c). A clustered cardiometabolic risk score was calculated. Linear regression analysis examined the associations with cardiometabolic health. Results There were 1457 participants (mean age [± standard deviation], 59.38 ± 11.85 yr; 51.7% male; mean BMI, 30.19 ± 5.59 kg·m−2) included in the analyses. ActivPAL and ActiGraph sedentary variables were moderately correlated (0.416–0.511, P < 0.01); however, all variables were significantly different from each other (P < 0.05). Consistency was observed across devices in the direction and magnitude of associations of TST and PST with adiposity, surrogate markers of adiposity, HDL, triglycerides, and cardiometabolic risk score and for BST with adiposity, surrogate markers of adiposity, and cardiometabolic risk. Differences across devices were observed in associations of TST and PST with diastolic blood pressure, for TST with 2-h glucose and for BST with HDL. No other associations were observed for any other health marker for either device. Conclusions Results suggest that associations with cardiometabolic health are largely comparable across the two common assessments of sedentary behavior but some small differences may exist for certain health markers

Promoting physical activity in a multi-ethnic population at high risk of diabetes: the 48-month PROPELS randomised controlled trial.

BackgroundPhysical activity is associated with a reduced risk of type 2 diabetes and cardiovascular disease but limited evidence exists for the sustained promotion of increased physical activity within diabetes prevention trials. The aim of the study was to investigate the long-term effectiveness of the Walking Away programme, an established group-based behavioural physical activity intervention with pedometer use, when delivered alone or with a supporting mHealth intervention.MethodsThose at risk of diabetes (nondiabetic hyperglycaemia) were recruited from primary care, 2013-2015, and randomised to (1) Control (information leaflet); (2) Walking Away (WA), a structured group education session followed by annual group-based support; or (3) Walking Away Plus (WAP), comprising WA annual group-based support and an mHealth intervention delivering tailored text messages supported by telephone calls. Follow-up was conducted at 12 and 48 months. The primary outcome was accelerometer measured ambulatory activity (steps/day). Change in primary outcome was analysed using analysis of covariance with adjustment for baseline, randomisation and stratification variables.ResultsOne thousand three hundred sixty-six individuals were randomised (median age = 61 years, ambulatory activity = 6638 steps/day, women = 49%, ethnic minorities = 28%). Accelerometer data were available for 1017 (74%) individuals at 12 months and 993 (73%) at 48 months. At 12 months, WAP increased their ambulatory activity by 547 (97.5% CI 211, 882) steps/day compared to control and were 1.61 (97.5% CI 1.05, 2.45) times more likely to achieve 150 min/week of moderate-to-vigorous physical activity. Differences were not maintained at 48 months. WA was no different to control at 12 or 48 months. Secondary anthropometric and health outcomes were largely unaltered in both intervention groups apart from small reductions in body weight in WA (~ 1 kg) at 12- and 48-month follow-up.ConclusionsCombining a pragmatic group-based intervention with text messaging and telephone support resulted in modest changes to physical activity at 12 months, but changes were not maintained at 48 months.Trial registrationISRCTN 83465245 (registered on 14 June 2012)

The association between air pollution and type 2 diabetes in a large cross-sectional study in Leicester: The CHAMPIONS Study

Background: Observational evidence suggests there is an association between air pollution and type 2 diabetes; however, there is high risk of bias. Objective: To investigate the association between air pollution and type 2 diabetes, while reducing bias due to exposure assessment, outcome assessment, and confounder assessment. Methods: Data were collected from 10,443 participants in three diabetes screening studies in Leicestershire, UK. Exposure assessment included standard, prevailing estimates of outdoor nitrogen dioxide and particulate matter concentrations in a 1 × 1 km area at the participant's home postcode. Three-year exposure was investigated in the primary analysis and one-year exposure in a sensitivity analysis. Outcome assessment included the oral glucose tolerance test for type 2 diabetes. Confounder assessment included demographic factors (age, sex, ethnicity, smoking, area social deprivation, urban or rural location), lifestyle factors (body mass index and physical activity), and neighbourhood green space. Results: Nitrogen dioxide and particulate matter concentrations were associated with type 2 diabetes in unadjusted models. There was no statistically significant association between nitrogen dioxide concentration and type 2 diabetes after adjustment for demographic factors (odds: 1.08; 95% CI: 0.91, 1.29). The odds of type 2 diabetes was 1.10 (95% CI: 0.92, 1.32) after further adjustment for lifestyle factors and 0.91 (95% CI: 0.72, 1.16) after yet further adjustment for neighbourhood green space. The associations between particulate matter concentrations and type 2 diabetes were also explained away by demographic factors. There was no evidence of exposure definition bias. Conclusions: Demographic factors seemed to explain the association between air pollution and type 2 diabetes in this cross-sectional study. High-quality longitudinal studies are needed to improve our understanding of the association

Metabolic effects of breaking prolonged sitting with standing or light walking in older South Asians and White Europeans: a randomized acute study

Background: Prolonged sitting is common in older adults and associated with insulin resistance and poor cardiometabolic health. We investigate whether breaking prolonged sitting with regular short bouts of standing or light walking improves postprandial metabolism in older white European and South Asian adults and whether effects are modified by ethnic group. Methods: Thirty South Asian (15 women) and 30 white European (14 women) older adults (65-79 years) undertook three experimental conditions in random order. 1) Prolonged sitting: continuous sitting during a 7.5 h observation period consuming two standardised mixed meals. 2) Standing breaks: sitting interrupted with 5 mins of standing every 30 mins (accumulating 60 mins of standing over the observation period). 3) Walking Breaks: sitting interrupted with 5 mins of self-paced light walking every 30 mins (accumulating 60 mins of walking). Blood samples (glucose, insulin, triglycerides) and blood pressure were sampled regularly throughout each condition. Results: Compared with prolonged sitting, walking breaks lowered postprandial insulin by 16.3 mU/l, (95% CI 19.7, 22.0) with greater reductions (p = 0.029) seen in South Asians (22.4 mU/l; 12.4, 32.4) than White Europeans (10.3 mU/l; 5.9, 14.7). Glucose (0.3 mmol/l; 0.1, 0.5) and blood pressure (4 mmHg; 2, 6), but not triglycerides, were lower with walking breaks, with no ethnic differences. Standing breaks did not improve any outcome. Conclusions: Breaking prolonged sitting with short bouts of light walking, but not standing, resulted in clinically meaningful improvements in markers of metabolic health in older adults, with South Asians gaining a greater reduction in postprandial insulin