Circulating fragments of N-Terminal Pro-B-Type Natriuretic Peptides in plasma of heart failure patients

BACKGROUND: The use of nonstandardized N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS: Plasma samples were collected from HF patients (n = 20) at rest and stored at -80 degrees C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA (R) immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS: Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS: In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule. (c) 2013 American Association for Clinical Chemistry

Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease

Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21–24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD

Phosphorylation of caveolin-1 is anti-apoptotic and promotes cell attachment during oxidative stress of kidney cells

Aims: Caveolin-1 (cav1) is reported to have both cell survival and pro-apoptotic characteristics. This may be explained by its localisation or phosphorylation in injured cells. This study investigated the role of cav1 in kidney cells of different nephron origin and developmental state after oxidative stress. Methods: Renal MCDK distal tubular, HK2 proximal tubular epithelial cells and HEK293T renal embryonic cells were treated with 1mM hydrogen peroxide. Apoptosis, loss of cell adhesion, and cell survival were compared with expression of cav1 in its non-phosphorylated and phosphorylated (p-cav1) forms. Cav1 was transfected into the HEK293T cells, or caveolae were disrupted with filipin or nystatin in HK2 cells, to investigate functions of cav1 and p-cav1. Results: Oxidative stress induced more apoptosis in HK2s than MDCKs (p<0.05). HK2s had lower endogenous cav1 and p-cav1 than MDCKs (p<0.05). Both cell lines had increased p-cav1, but not cav1, with oxidative stress. This increase was greatest in MDCKs (p<0.01). Cav1 was located mainly in the plasma membrane of untreated cells and translocated to the cytoplasm with oxidative stress in both cell lines, more so in MDCKs. Disruption of caveolae caused cytoplasmic translocation of cav1 in HK2s, but did not alter high levels of oxidative stress-induced apoptosis. When HEK293Ts lacking endogenous cav1 were transfected with cav1, oxidant-induced apoptosis and loss of cell adhesion was decreased (p<0.01), and p-cav1 was induced by treatment. Conclusion: Cav1 expression and localisation in kidney cells is not anti-apoptotic, but increased expression of p-cav1 may promote cell survival after oxidative stress. © 2008 Royal College of Pathologists of Australasia.

Synthesis, characterization and activity of an immobilized photocatalyst : natural porous diatomite supported titania nanoparticles

Diatomite, a porous non-metal mineral, was used as support to prepare TiO2/diatomite composites by a modified sol–gel method. The as-prepared composites were calcined at temperatures ranging from 450 to 950 _C. The characterization tests included X-ray powder diffraction (XRD), scanning electron microscopy (SEM) with an energy-dispersive X-ray spectrometer (EDS), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and nitrogen adsorption/desorption measurements. The XRD analysis indicated that the binary mixtures of anatase and rutile exist in the composites. The morphology analysis confirmed the TiO2 particles were uniformly immobilized on the surface of diatom with a strong interfacial anchoring strength, which leads to few drain of photocatalytic components during practical applications. In further XPS studies of hybrid catalyst, we found the evidence of the presence of Ti–O–Si bond and increased percentage of surface hydroxyl. In addition, the adsorption capacity and photocatalytic activity of synthesized TiO2/diatomite composites were evaluated by studying the degradation kinetics of aqueous Rhodamine B under UV-light irradiation. The photocatalytic degradation was found to follow pseudo-first order kinetics according to the Langmuir–Hinshelwood model. The preferable removal efficiency was observed in composites by 750 _C calcination, which is attributed to a relatively appropriate anatase/rutile mixing ratio of 90/10.

Design for creative activity : a framework for analyzing the creative potential of computer games

This paper describes a design framework intended to conceptually map the influence that game design has on the creative activity people engage in during gameplay. The framework builds on behavioral and verbal analysis of people playing puzzle games. The analysis was designed to better understand the extent to which gameplay activities within different games facilitate creative problem solving. We have used an expert review process to evaluate these games in terms of their game design elements and have taken a cognitive action approach to this process to investigate how particular elements produce the potential for creative activity. This paper proposes guidelines that build upon our understanding of the relationship between the creative processes that players undertake during a game and the components of the game that allow these processes to occur. These guidelines may be used in the game design process to better facilitate creative gameplay activity.

Machine learning for activity recognition : hip versus wrist data

Problem addressed Wrist-worn accelerometers are associated with greater compliance. However, validated algorithms for predicting activity type from wrist-worn accelerometer data are lacking. This study compared the activity recognition rates of an activity classifier trained on acceleration signal collected on the wrist and hip. Methodology 52 children and adolescents (mean age 13.7 +/- 3.1 year) completed 12 activity trials that were categorized into 7 activity classes: lying down, sitting, standing, walking, running, basketball, and dancing. During each trial, participants wore an ActiGraph GT3X+ tri-axial accelerometer on the right hip and the non-dominant wrist. Features were extracted from 10-s windows and inputted into a regularized logistic regression model using R (Glmnet + L1). Results Classification accuracy for the hip and wrist was 91.0% +/- 3.1% and 88.4% +/- 3.0%, respectively. The hip model exhibited excellent classification accuracy for sitting (91.3%), standing (95.8%), walking (95.8%), and running (96.8%); acceptable classification accuracy for lying down (88.3%) and basketball (81.9%); and modest accuracy for dance (64.1%). The wrist model exhibited excellent classification accuracy for sitting (93.0%), standing (91.7%), and walking (95.8%); acceptable classification accuracy for basketball (86.0%); and modest accuracy for running (78.8%), lying down (74.6%) and dance (69.4%). Potential Impact Both the hip and wrist algorithms achieved acceptable classification accuracy, allowing researchers to use either placement for activity recognition.

Advances in the science of objective physical activity monitoring : 3rd International Conference on Ambulatory Monitoring of Physical Activity and Movement

Editorial: This theme issue of BJSM presents key papers from the 3rd International Conference on Ambulatory Monitoring of Physical Activity and Movement (ICAMPAM). The July 2013 conference was hosted by the University of Massachusetts and was attended by researchers, clinicians, students and technology vendors for North America, Europe, Australasia and Asia...

Use of physical activity self-management strategies by high school students

Teaching adolescents to use self-management strategies (SMS's) may be an effective approach to promoting lifelong physical activity (PA). However, the extent to which adolescents use SMS's and their impact on current PA have not been studied previously. The aims of this study were: 1) describe the prevalence of SMS use in adolescents; and 2) determine relationships between SMS use, PA self-efficacy, and PA participation. 197 students completed questionnaires measuring use of SMS's, self-efficacy, and PA behavior. The most prevalent SMS's (>30%) were thinking about the benefits of PA, making PA more enjoyable, choosing activities that are convenient, setting aside time to do PA, and setting goals to do PA. Less than 10% reported rewarding oneself for PA, writing planned activities in a book or calendar, and keeping charts of PA. SMS use was associated with increased self-efficacy (r = 0.47, P < .001) and higher levels of PA (r = 0.34 P < .001). A one unit difference in SMS scores was associated with a ~ 4-fold increase in the probability of being active (OR = 3.7, 95% CI = 1.8-7.4). Although strongly associated with PA, a relatively small percentage of adolescents routinely use SMS's.

Activity patterns of preschool-aged children at risk for obesity

BACKGROUND Although the prevalence of obesity in young children highlights the importance of early interventions to promote physical activity (PA), there are limited data on activity patterns in this age group. The purpose of this study is to describe activity patterns in preschool-aged children and explore differences by weight status. METHODS Analyses use baseline data from Healthy Homes/Healthy Kids- Preschool, a pilot obesity prevention trial of preschool-aged children overweight or at risk for overweight. A modified parent-reported version of the previous-day PA recall was used to summarize types of activity. Accelerometry was used to summarize daily and hourly activity patterns. RESULTS "Playing with toys" accounted for the largest proportion of a child's previous day, followed by "meals and snacks", and "chores". Accelerometry-measured daily time spent in sedentary behavior, light PA, and moderate-to-vigorous PA (MVPA) was 412, 247, and 69 minutes, respectively. Percent of hourly time spent in MVPA ranged from 3% to 13%, peaking in the late morning and evening hours. There were no statistically significant MVPA differences by weight status. CONCLUSIONS This study extends our understanding of activity types, amounts, and patterns in preschool-age children and warrants further exploration of differences in physical activity patterns by weight status.

Evaluating the responsiveness of accelerometry to detect change in physical activity

The responsiveness to change of the Actical and ActiGraph accelerometers was assessed in children and adolescents. Participants (n=208) aged 6-16 years completed two simulated free-living protocols, one with primarily light-to-moderate physical activities (PA) and one with mostly moderate-to-vigorous PA. Time in sedentary, light, moderate, and vigorous PA was estimated using 8 previously developed cut-points (4 for Actical and 4 for ActiGraph) and 15-s and 30-s epochs. Accelerometer responsiveness for detecting differences in PA between protocols was assessed using standardized response means (SRM). SRM values >/=0.8 represented high responsiveness to change. Both accelerometers showed high responsiveness for all PA intensities (SRMs = 1.2-4.7 for Actical and 1.1-3.3 for ActiGraph). All cut-points and epoch lengths yielded high responsiveness, and choice of cut-points and epoch length had little effect on responsiveness. Thus, both the Actical and ActiGraph can detect change in PA in a simulated free-living setting, irrespective of cut-point selection or epoch length.

How are falls and fear of falling associated with objectively measured physical activity in a cohort of community-dwelling older men?

BACKGROUND: Falls affect approximately one third of community-dwelling older adults each year and have serious health and social consequences. Fear of falling (FOF) (lack of confidence in maintaining balance during normal activities) affects many older adults, irrespective of whether they have actually experienced falls. Both falls and fear of falls may result in restrictions of physical activity, which in turn have health consequences. To date the relation between (i) falls and (ii) fear of falling with physical activity have not been investigated using objectively measured activity data which permits examination of different intensities of activity and sedentary behaviour. METHODS: Cross-sectional study of 1680 men aged 71-92 years recruited from primary care practices who were part of an on-going population-based cohort. Men reported falls history in previous 12 months, FOF, health status and demographic characteristics. Men wore a GT3x accelerometer over the hip for 7 days. RESULTS: Among the 12% of men who had recurrent falls, daily activity levels were lower than among non-fallers; 942 (95% CI 503, 1381) fewer steps/day, 12(95% CI 2, 22) minutes less in light activity, 10(95% CI 5, 15) minutes less in moderate to vigorous PA [MVPA] and 22(95% CI 9, 35) minutes more in sedentary behaviour. 16% (n = 254) of men reported FOF, of whom 52% (n = 133) had fallen in the past year. Physical activity deficits were even greater in the men who reported that they were fearful of falling than in men who had fallen. Men who were fearful of falling took 1766(95% CI 1391, 2142) fewer steps/day than men who were not fearful, and spent 27(95% CI 18, 36) minutes less in light PA, 18(95% CI 13, 22) minutes less in MVPA, and 45(95% CI 34, 56) minutes more in sedentary behaviour. The significant differences in activity levels between (i) fallers and non-fallers and (ii) men who were fearful of falling or not fearful, were mediated by similar variables; lower exercise self-efficacy, fewer excursions from home and more mobility difficulties. CONCLUSIONS: Falls and in particular fear of falling are important barriers to older people gaining health benefits of walking and MVPA. Future studies should assess the longitudinal associations between falls and physical activity.

A review of preschool children's physical activity and sedentary time using objective measures

CONTEXT: Identifying current physical activity levels and sedentary time of preschool children is important for informing government policy and community initiatives. This paper reviewed studies reporting on physical activity and time spent sedentary among preschool-aged children (2-5 years) using objective measures. EVIDENCE ACQUISITION: Databases were searched for studies published up to and including April 2013 that reported on, or enabled the calculation of, the proportion of time preschool children spent sedentary and in light- and moderate to vigorous-intensity physical activity. A total of 40 publications met the inclusion criteria for physical activity and 31 met the inclusion criteria for sedentary time. Objective measures included ActiGraph, Actiwatch, Actical, Actiheart, and RT3 accelerometers, direct observation, and Quantum XL telemetry heart rate monitoring. Data were analyzed in May 2013. EVIDENCE SYNTHESIS: Considerable variation in prevalence estimates existed. The proportion of time children spent sedentary ranged from 34% to 94%. The time spent in light-intensity physical activity and moderate to vigorous-intensity physical activity ranged from 4% to 33% and 2% to 41%, respectively. CONCLUSIONS: The considerable variation of prevalence estimates makes it difficult to determine the "true" prevalence of physical activity and sedentary time in preschool children. Future research should aim to reduce inconsistencies in the employed methodologies to better understand preschoolers' physical activity levels and sedentary behavior.

Prediction of activity type in preschool children using machine learning techniques

Objectives Recent research has shown that machine learning techniques can accurately predict activity classes from accelerometer data in adolescents and adults. The purpose of this study is to develop and test machine learning models for predicting activity type in preschool-aged children. Design Participants completed 12 standardised activity trials (TV, reading, tablet game, quiet play, art, treasure hunt, cleaning up, active game, obstacle course, bicycle riding) over two laboratory visits. Methods Eleven children aged 3–6 years (mean age = 4.8 ± 0.87; 55% girls) completed the activity trials while wearing an ActiGraph GT3X+ accelerometer on the right hip. Activities were categorised into five activity classes: sedentary activities, light activities, moderate to vigorous activities, walking, and running. A standard feed-forward Artificial Neural Network and a Deep Learning Ensemble Network were trained on features in the accelerometer data used in previous investigations (10th, 25th, 50th, 75th and 90th percentiles and the lag-one autocorrelation). Results Overall recognition accuracy for the standard feed forward Artificial Neural Network was 69.7%. Recognition accuracy for sedentary activities, light activities and games, moderate-to-vigorous activities, walking, and running was 82%, 79%, 64%, 36% and 46%, respectively. In comparison, overall recognition accuracy for the Deep Learning Ensemble Network was 82.6%. For sedentary activities, light activities and games, moderate-to-vigorous activities, walking, and running recognition accuracy was 84%, 91%, 79%, 73% and 73%, respectively. Conclusions Ensemble machine learning approaches such as Deep Learning Ensemble Network can accurately predict activity type from accelerometer data in preschool children.

Moderate physical activity level as a protective factor against metabolic syndrome in middle-aged and older women

Aims and objectives To investigate whether physical activity is a protective factor against metabolic syndrome in middle-aged and older women. Background Socio-demographic and lifestyle behaviour factors contribute to metabolic syndrome. To minimise the risk of metabolic syndrome, several global guidelines recommend increasing physical activity level. However, only limited research has investigated the relationship between physical activity levels and metabolic syndrome in middle-aged and older women after adjusting for socio-demographic and lifestyle behaviour factors. Design Cross-sectional design. Methods A convenience sample of 326 middle-aged and older women was recruited. Metabolic syndrome was confirmed according to the National Cholesterol Education Program, Adult Treatment Panel III guidelines, and physical activity levels were measured by the International Physical Activity Questionnaire. Results The sample had a mean age of 60•9 years, and the prevalence of metabolic syndrome was 43•3%. Postmenopausal women and women with low socioeconomic status (low-education background, without personal income and currently unemployed) had a significantly higher risk of developing metabolic syndrome. After adjusting for significant socio-demographic and lifestyle behaviour factors, the women with moderate or high physical activity levels had a significantly lower (OR = 0•10; OR = 0•11, p < 0•001) risk of metabolic syndrome and a lower risk for each specific component of metabolic syndrome, including elevated fasting plasma glucose (OR = 0•29; OR = 0•26, p = 0•009), elevated blood pressure (OR = 0•18; OR = 0•32, p = 0•029), elevated triglycerides (OR = 0•41; OR = 0•15, p = 0•001), reduced high-density lipoprotein (OR = 0•28; OR = 0•27, p = 0•004) and central obesity (OR = 0•31; OR = 0•22, p = 0•027). Conclusions After adjusting for socio-demographic and lifestyle behaviour factors, physical activity level was a significant protective factor against metabolic syndrome in middle-aged and older women. Higher physical activity levels (moderate or high physical activity level) reduced the risk of metabolic syndrome in middle-aged and older women. Relevance to clinical practice Appropriate strategies should be developed to encourage middle-aged and older women across different socio-demographic backgrounds to engage in moderate or high levels of physical activity to reduce the risk of metabolic syndrome.

Exploring parents' beliefs about their young child's physical activity and screen time behaviours

Drawing on the belief-based framework of the theory of planned behaviour, 20 adults living in Queensland, Australia participated in semi-structured interviews to elicit salient beliefs regarding their young child’s physical activity (PA) and screen time behaviours. Data were analysed separately for PA and screen time with a range of beliefs emerging that guided parents’ decisions for these important health behaviours. Underlying advantages (e.g., improve family interactions, improve child behaviour), disadvantages (e.g., mess and noise factor, increase in parental distress), barriers (e.g., lack of time, parental fatigue), and facilitators (e.g., access to parks, social support) to engaging their child in adequate PA and limited screen time emerged. Normative pressures were also identified as affecting parents’ decisions for their child in these contexts. Parents experience unique difficulties in engaging their child in adequate PA and limited screen time that interventions can draw on when designing and implementing programs aimed at modifying these important child health behaviours.