Hyaluronan Modulated Expression of MMPs 2, 9, and 12 in Macrophages

Hyaluronan (HA) is a ubiquitously expressed Glycosaminoglycan (GAG) found as a main component of the extracellular matrix (ECM). Matrix metalloproteases (MMPs) are class of enzyme responsible for the degradation of multiple ECM components, including HA. Following a myocardial infarction (MI), ECM remodeling occurs in the infarct tissue and involves an accumulation of HA. Remodeling is facilitated by multiple cell types, including macrophages. During post-MI ECM remodeling, macrophages degrade and ingulf dead cells and ECM components, a process which requires the expression of MMPs. MMPs 2, 9, and 12 are known to be elevated post-MI; MMPs 9 and 12 are known to have HA as a substrate. These factors make MMPs 2, 9, and 12 especially relevant to the post-MI ECM remodeling process. The effect of increased HA present post-MI on levels of MMP expression in macrophages has yet to be investigated

Optimal Weighting of Preclinical Alzheimer’s Cognitive Composite (PACC) Scales to Improve their Performance as Outcome Measures for Alzheimer’s Disease Clinical Trials

Introduction: Cognitive composite scales constructed by combining existing neuropsychometric tests are seeing wide application as endpoints for clinical trials and cohort studies of Alzheimer’s disease (AD) predementia conditions. Preclinical Alzheimer’s Cognitive Composite (PACC) scales are composite scores calculated as the sum of the component test scores weighted by the reciprocal of their standard deviations at the baseline visit. Reciprocal standard deviation is an arbitrary weighting in this context, and may be an inefficient utilization of the data contained in the component measures. Mathematically derived optimal composite weighting is a promising alternative. Methods: Sample size projections using standard power calculation formulas were used to describe the relative performance of component measures and their composites when used as endpoints for clinical trials. Power calculations were informed by (n=1,333) amnestic mild cognitive impaired participants in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. Results: A composite constructed using PACC reciprocal standard deviation weighting was both less sensitive to change than one of its component measures and less sensitive to change than its optimally weighted counterpart. In standard sample size calculations informed by NACC data, a clinical trial using the PACC weighting would require 38% more subjects than a composite calculated using optimal weighting. Discussion: These findings illustrate how reciprocal standard deviation weighting can result in inefficient cognitive composites, and underscore the importance of component weights to the performance of composite scales. In the future, optimal weighting parameters informed by accumulating clinical trial data may improve the efficiency of clinical trials in AD

Infrared Lightcurves of Near Earth Objects

We present lightcurves and derive periods and amplitudes for a subset of 38 near earth objects (NEOs) observed at 4.5 microns with the IRAC camera on the the Spitzer Space Telescope, many of them having no previously reported rotation periods. This subset was chosen from about 1800 IRAC NEO observations as having obvious periodicity and significant amplitude. For objects where the period observed did not sample the full rotational period, we derived lower limits to these parameters based on sinusoidal fits. Lightcurve durations ranged from 42 to 544 minutes, with derived periods from 16 to 400 minutes. We discuss the effects of lightcurve variations on the thermal modeling used to derive diameters and albedos from Spitzer photometry. We find that both diameters and albedos derived from the lightcurve maxima and minima agree with our previously published results, even for extreme objects, showing the conservative nature of the thermal model uncertainties. We also evaluate the NEO rotation rates, sizes, and their cohesive strengths.Comment: 16 pages, 4 figures, 3 tables, to appear in the Astrophysical Journal Supplement Serie

Patterns of Sedentary Behavior and Mortality in U.S. Middle-Aged and Older Adults: A National Cohort Study

Background: Excessive sedentary time is ubiquitous in Western societies. Previous studies have relied on self-reporting to evaluate the total volume of sedentary time as a prognostic risk factor for mortality and have not examined whether the manner in which sedentary time is accrued (in short or long bouts) carries prognostic relevance. Objective: To examine the association between objectively measured sedentary behavior (its total volume and accrual in prolonged, uninterrupted bouts) and all-cause mortality. Design: Prospective cohort study. Setting: Contiguous United States. Participants: 7985 black and white adults aged 45 years or older. Measurements: Sedentary time was measured using a hip-mounted accelerometer. Prolonged, uninterrupted sedentariness was expressed as mean sedentary bout length. Hazard ratios (HRs) were calculated comparing quartiles 2 through 4 to quartile 1 for each exposure (quartile cut points: 689.7, 746.5, and 799.4 min/d for total sedentary time; 7.7, 9.6, and 12.4 min/bout for sedentary bout duration) in models that included moderate to vigorous physical activity. Results: Over a median follow-up of 4.0 years, 340 participants died. In multivariable-adjusted models, greater total sedentary time (HR, 1.22 [95% CI, 0.74 to 2.02]; HR, 1.61 [CI, 0.99 to 2.63]; and HR, 2.63 [CI, 1.60 to 4.30]; P for trend < 0.001) and longer sedentary bout duration (HR, 1.03 [CI, 0.67 to 1.60]; HR, 1.22 [CI, 0.80 to 1.85]; and HR, 1.96 [CI, 1.31 to 2.93]; P for trend < 0.001) were both associated with a higher risk for all-cause mortality. Evaluation of their joint association showed that participants classified as high for both sedentary characteristics (high sedentary time [≥12.5 h/d] and high bout duration [≥10 min/bout]) had the greatest risk for death. Limitation: Participants may not be representative of the general U.S. population. Conclusion: Both the total volume of sedentary time and its accrual in prolonged, uninterrupted bouts are associated with all-cause mortality, suggesting that physical activity guidelines should target reducing and interrupting sedentary time to reduce risk for death

Association Between Objectively Measured Physical Activity and Cognitive Function in Older Adults—The Reasons for Geographic and Racial Differences in Stroke Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116310/1/jgs13829_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116310/2/jgs13829.pd

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published or submitted for publicationis peer reviewedOpe

Patient-centred approaches to providing care at HIV diagnosis: perspectives from healthcare and peer-support workers

Background. Early uptake of HIV treatment among those newly diagnosed with HIV can improve individual health and prevent onward transmission. Patient-centred care is considered an important aspect in health care, the management of HIV, and can improve uptake of and adherence to HIV treatments. Methods. Semi-structured interviews were conducted with sexual health clinicians (n, 10) and HIV support workers (n, 4) to understand how they approached HIV diagnosis delivery and care immediately thereafter. Results. Our thematic analysis identified three themes: (1) centring patient needs at diagnosis; (2) assessing patients’ readiness to begin treatment; and (3) referrals to psychosocial support services. Our findings highlight centring patients was an important aspect of how participants delivered HIV diagnoses. By taking this approach, clinicians were best able to consider patient readiness to initiate treatment and referrals to social support services. Conclusions. Given HIV diagnoses are increasingly occurring in generalist health services, our findings offer an important opportunity to learn from the experiences of specialist sexual health clinicians and HIV support workers

Impacts of Creatine Supplementation on Running Anaerobic Sprint Performance Test (RAST) Power and Velocity in Youth Soccer Players

Creatine supplementation commonly enhances short-term, high-intensity effort performance such the soccer-specific ability to perform repeated sprints. Research in this regard is both generally sparse but specifically more so in youth athletes. PURPOSE: to determine the effect of 28 days of creatine monohydrate supplementation on running anaerobic sprint performance (RAST) power and velocity in youth soccer players. METHODS: Sixteen male youth soccer players were randomized in double-blinded, parallel-group fashion to either 28 days of creatine supplementation (CRE; 15.9±0.35y) or an equivalently-dosed dextrose (PLA; 15.5±0.54y; 0.3g/kg/d loading dose for the first seven days, followed by 0.03g/kg/d for the remaining period), whereby they maintained their typical diet and training routines throughout the study. Furthermore, all subjects measured their weight and performed two RAST tests both prior to (PRE) and following (POST) supplementation, consisting of 10 second rest intervals between six maximal 35m runs. RAST peak and mean values for power and velocity were determined via a Speed Test FIT CEFISE photocell system. Due to the data’s distribution, individual appropriate within- and between-group nonparametric analyses were employed to assess PRE-to-POST supplementation mean and peak power (mP and pP) and velocity (mV and pV) at a significance level of p\u3c.05. RESULTS: Neither power parameter (mP and pP) nor pV differed PRE-to-POST or between groups (p\u3e.05). Nevertheless, nonparametric analyses revealed statistically significant mV differences (p=.025), whereby post-supplementation CRE was greater (23.7±1.64km/h) compared to both PRE in either group (CRE-PRE: 22.9±1.81km/h; PLA-PRE: 22.1±0.638km/h) and relative to PLA post-supplementation (22.2±1.15km/h). CONCLUSION: Although creatine supplementation did not meaningfully enhance RAST-associated power nor peak velocity, it did enhance mean velocity in youth soccer athletes. Notwithstanding our limited ability to claim a creatine-mediated performance advantage in this and similar demographics, future research should corroborate and further support these data by employing a standardized training protocol to eliminate additional extraneous variables

"GET-UP" study rationale and protocol: A cluster randomised controlled trial to evaluate the effects of reduced sitting on toddlers' cognitive development

Background: The educational and cognitive differences associated with low socioeconomic status begin early in life and tend to persist throughout life. Coupled with the finding that levels of sedentary time are negatively associated with cognitive development, and time spent active tends to be lower in disadvantaged circumstances, this highlights the need for interventions that reduce the amount of time children spend sitting and sedentary during childcare. The proposed study aims to assess the effects of reducing sitting time during Early Childhood Education and Care (ECEC) services on cognitive development in toddlers from low socio-economic families. Methods/Design: We will implement a 12-months 2-arm parallel group cluster randomised controlled trial (RCT) with Australian toddlers, aged 12 to 26 months at baseline. Educators from the ECEC services allocated to the intervention group will receive professional development on how to reduce sitting time while children attend ECEC. Participants' cognitive development will be assessed as a primary outcome, at baseline and post-intervention, using the cognitive sub-test from the Bayley Scales of Infant and Toddler Development. Discussion: This trial has the potential to inform programs and policies designed to optimize developmental and health outcomes in toddlers, specifically in those from disadvantaged backgrounds