196 research outputs found
The de Morton Mobility Index (DEMMI): An essential health index for an ageing world
BACKGROUND: Existing instruments for measuring mobility are inadequate for accurately assessing older people across the broad spectrum of abilities. Like other indices that monitor critical aspects of health such as blood pressure tests, a mobility test for all older acute medical patients provides essential health data. We have developed and validated an instrument that captures essential information about the mobility status of older acute medical patients. METHODS: Items suitable for a new mobility instrument were generated from existing scales, patient interviews and focus groups with experts. 51 items were pilot tested on older acute medical inpatients. An interval-level unidimensional mobility measure was constructed using Rasch analysis. The final item set required minimal equipment and was quick and simple to administer. The de Morton Mobility Index (DEMMI) was validated on an independent sample of older acute medical inpatients and its clinimetric properties confirmed. RESULTS: The DEMMI is a 15 item unidimensional measure of mobility. Reliability (MDC(90)), validity and the minimally clinically important difference (MCID) of the DEMMI were consistent across independent samples. The MDC(90) and MCID were 9 and 10 points respectively (on the 100 point Rasch converted interval DEMMI scale). CONCLUSION: The DEMMI provides clinicians and researchers with a valid interval-level method for accurately measuring and monitoring mobility levels of older acute medical patients. DEMMI validation studies are underway in other clinical settings and in the community. Given the ageing population and the importance of mobility for health and community participation, there has never been a greater need for this instrument
Fruit and Vegetable Bucks: Adams County Grocery Store Snap Incentive Program
Veggie Bucks provides a 50% discount on all fresh fruits and vegetables sold through Kennie’s Market produce department at the point of sale for the 5 highest cost items. The incentive period ran January - April, 2017. Intended outcomes include an increase in the number of fresh fruits and vegetables purchased by SNAP recipients at Kennie’s Market locations in Biglerville and Gettysburg by 10% in January-April 2017 compared to baseline figures obtained in 2016, and to familiarize SNAP recipients with fresh fruits and vegetables and to provide information about the ACFMA markets’ Double Dollars program. SNAP recipients were invited to sign up for the program upon showing their ID and EBT card and were provided a Kennie\u27s Frequent Shopper card if they did not have one already
An Improved Cerulean Fluorescent Protein with Enhanced Brightness and Reduced Reversible Photoswitching
Cyan fluorescent proteins (CFPs), such as Cerulean, are widely used as donor
fluorophores in Förster resonance energy transfer (FRET) experiments.
Nonetheless, the most widely used variants suffer from drawbacks that include
low quantum yields and unstable flurorescence. To improve the fluorescence
properties of Cerulean, we used the X-ray structure to rationally target
specific amino acids for optimization by site-directed mutagenesis. Optimization
of residues in strands 7 and 8 of the β-barrel improved the quantum yield of
Cerulean from 0.48 to 0.60. Further optimization by incorporating the wild-type
T65S mutation in the chromophore improved the quantum yield to 0.87. This
variant, mCerulean3, is 20% brighter and shows greatly reduced
fluorescence photoswitching behavior compared to the recently described
mTurquoise fluorescent protein in vitro and in living cells. The fluorescence
lifetime of mCerulean3 also fits to a single exponential time constant, making
mCerulean3 a suitable choice for fluorescence lifetime microscopy experiments.
Furthermore, inclusion of mCerulean3 in a fusion protein with mVenus produced
FRET ratios with less variance than mTurquoise-containing fusions in living
cells. Thus, mCerulean3 is a bright, photostable cyan fluorescent protein which
possesses several characteristics that are highly desirable for FRET
experiments
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.
It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6-8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution
ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Na(v)1.8(+) sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Na(v)1.8(+) sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons. SIGNIFICANCE STATEMENT ERK1/2 signaling affects sensory neuron function and survival. However, it was not clear whether ERK isoform-specific roles exist in these processes postnatally. Previous work from our laboratory suggested either functional redundancy of ERK isoforms or a predominant role for ERK2 in pain; however, the tools to discriminate between these possibilities were not available at the time. In the present study, we use new genetic knock-out lines to demonstrate that ERK2 in sensory neurons is necessary for development of inflammatory pain and for postnatal maintenance of peptidergic epidermal innervation. Interestingly, postnatal loss of both ERK isoforms leads to a profound loss of sensory neurons. Therefore, ERK1 and ERK2 display both functionally distinct and redundant roles in sensory neurons
Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial
Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety
Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial
Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety
A novel μCT analysis reveals different responses of bioerosion and secondary accretion to environmental variability
Corals build reefs through accretion of calcium carbonate (CaCO3) skeletons, but net reef growth also depends on bioerosion by grazers and borers and on secondary calcification by crustose coralline algae and other calcifying invertebrates. However, traditional field methods for quantifying secondary accretion and bioerosion confound both processes, do not measure them on the same time-scale, or are restricted to 2D methods. In a prior study, we compared multiple environmental drivers of net erosion using pre- and post-deployment micro-computed tomography scans (μCT; calculated as the % change in volume of experimental CaCO3 blocks) and found a shift from net accretion to net erosion with increasing ocean acidity. Here, we present a novel μCT method and detail a procedure that aligns and digitally subtracts pre- and post-deployment μCT scans and measures the simultaneous response of secondary accretion and bioerosion on blocks exposed to the same environmental variation over the same time-scale. We tested our method on a dataset from a prior study and show that it can be used to uncover information previously unattainable using traditional methods. We demonstrated that secondary accretion and bioerosion are driven by different environmental parameters, bioerosion is more sensitive to ocean acidity than secondary accretion, and net erosion is driven more by changes in bioerosion than secondary accretion
Exploring African lion (Panthera leo) behavioural phenotypes: individual differences and correlations between sociality, boldness and behaviour
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