A Review of Electronic Devices to Assess Inhaler Technique

Multiple electronic devices exist that provide feedback on the accuracy of patient inhaler technique. Our purpose is to describe the inhaler technique feedback provided by these devices, including specific technique steps measured, how feedback is displayed, target of feedback (patient, provider, researcher), and compatibility with inhaler type (metered-dose inhaler [MDI], diskus, etc.)

Learning environments’ activity potential for preschoolers (LEAPP): study rationale and design

Background. The purpose of this paper is to provide an overview of the study protocol for the Learning Environments’ Activity Potential for Preschoolers (LEAPP) study, the goal of which is to describe the activity levels of preschoolers attending various early learning venues and explore which attributes of these facilities (e.g. curriculum, policies, equipment, etc.) support activity participation.Design and Methods. This cross-sectional study aimed to recruit approximately 30 early learning environments requesting participation from preschoolers aged 2.5-5 years. Data collection included: Actical accelerometers (MiniMitter, Oregon, USA) to measure the activity levels of children for five consecutive days (15-second epoch length) while in care; the Environment and Policy Assessment and Observation tool to explore the early learning environment’s impact on activity; anthropometric data; the Child Temperament Questionnaire to assess the influence of preschoolers’ temperament on physical activity; and demographic information from parents/guardians and early learning staff. ANOVA and linear regression analyses will be conducted to assess variances in activity levels among preschoolers attending different early learning types and to explore the impact of early learning environments on their activity levels. Independent sample t-tests will be used to examine differences in activity levels based on sex and weight status.Expected impact of the study for public health. This research will provide the first Canadian data to address environmental influences on preschoolers’ activity levels in differing early learning environments. Additionally, this work will highlight the extent to which activity levels vary among preschoolers enrolled in full-day kindergarten, centre-, and home-based childcare

Lrp4 Regulates Initiation of Ureteric Budding and Is Crucial for Kidney Formation – A Mouse Model for Cenani-Lenz Syndrome

Background: Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. Methods and Principal Findings: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. Conclusion: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4 2/2 mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidne

Combinatorial lentiviral gene delivery of pro‐oligodendrogenic factors for improving myelination of regenerating axons after spinal cord injury

Spinal cord injury (SCI) results in paralysis below the injury and strategies are being developed that support axonal regrowth, yet recovery lags, in part, because many axons are not remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet‐derived growth factor (PDGF)‐AA and noggin either alone or in combination in a mouse SCI model. Noggin and PDGF‐AA have been identified as factors that enhance recruitment and differentiation of endogenous progenitors to promote myelination. Lentivirus encoding for these factors was delivered from a multichannel bridge, which we have previously shown creates a permissive environment and supports robust axonal growth through channels. The combination of noggin+PDGF enhanced total myelination of regenerating axons relative to either factor alone, and importantly, enhanced functional recovery relative to the control condition. The increase in myelination was consistent with an increase in oligodendrocyte‐derived myelin, which was also associated with a greater density of cells of an oligodendroglial lineage relative to each factor individually and control conditions. These results suggest enhanced myelination of regenerating axons by noggin+PDGF that act on oligodendrocyte‐lineage cells post‐SCI, which ultimately led to improved functional outcomes.Spinal cord injury (SCI) results in paralysis below the injury and strategies are being developed that support axonal regrowth, yet recovery lags, in part because many axons are not remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet‐derived growth factor‐AA and noggin either alone or in combination in a mouse SCI model.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146575/1/bit26838_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146575/2/bit26838.pd

Foldamers Reveal and Validate Therapeutic Targets Associated with Toxic α-Synuclein Self-Assembly

Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays is utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for effective treatments for PD

PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors

Patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor overall prognosis despite chemotherapy and radiotherapy (e.g., peptide receptor radionuclide therapy (PRRT)). Better treatment options are needed to improve disease regression and patient survival. The purpose of this study was to examine a new treatment strategy by combining PI3K/mTOR dual inhibition and radiotherapy. First, we assessed the efficacy of two PI3K/mTOR dual inhibitors, PF-04691502 and PKI-402, to inhibit pAkt and increase apoptosis in NET cell lines (BON and QGP-1) and patient-derived tumor spheroids as single agents or combined with radiotherapy (XRT). Treatment with PF-04691502 decreased pAkt (Ser473) expression for up to 72 h compared with the control; in contrast, decreased pAkt expression was noted for less than 24 h with PKI-402. Simultaneous treatment with PF-04691502 and XRT did not induce apoptosis in NET cells; however, the addition of PF-04691502 48 h after XRT significantly increased apoptosis compared to PF-04691502 or XRT treatment alone. Our results demonstrate that schedule-dependent administration of a PI3K/mTOR inhibitor, combined with XRT, can enhance cytotoxicity by promoting the radiosensitivity of NET cells. Moreover, our findings suggest that radiotherapy, in combination with timed PI3K/mTOR inhibition, may be a promising therapeutic regimen for patients with GEP-NET

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Testing the Asteroseismic Mass Scale Using Metal-Poor Stars Characterized with APOGEE and Kepler

Fundamental stellar properties, such as mass, radius, and age, can be inferred using asteroseismology. Cool stars with convective envelopes have turbulent motions that can stochastically drive and damp pulsations. The properties of the oscillation frequency power spectrum can be tied to mass and radius through solar-scaled asteroseismic relations. Stellar properties derived using these scaling relations need verification over a range of metallicities. Because the age and mass of halo stars are well-constrained by astrophysical priors, they provide an independent, empirical check on asteroseismic mass estimates in the low-metallicity regime. We identify nine metal-poor red giants (including six stars that are kinematically associated with the halo) from a sample observed by both the Kepler space telescope and the Sloan Digital Sky Survey-III APOGEE spectroscopic survey. We compare masses inferred using asteroseismology to those expected for halo and thick-disk stars. Although our sample is small, standard scaling relations, combined with asteroseismic parameters from the APOKASC Catalog, produce masses that are systematically higher (=0.17+/-0.05 Msun) than astrophysical expectations. The magnitude of the mass discrepancy is reduced by known theoretical corrections to the measured large frequency separation scaling relationship. Using alternative methods for measuring asteroseismic parameters induces systematic shifts at the 0.04 Msun level. We also compare published asteroseismic analyses with scaling relationship masses to examine the impact of using the frequency of maximum power as a constraint. Upcoming APOKASC observations will provide a larger sample of ~100 metal-poor stars, important for detailed asteroseismic characterization of Galactic stellar populations.Comment: 4 figures; 1 table. Accepted to ApJ

Effect of β2-adrenergic receptor stimulation on lung fluid in stable heart failure patients

Introduction: The purpose of this study was to determine 1) if stable heart-failure patients with reduced ejection fraction (HFrEF) have elevated extravascular lung water (EVLW) versus healthy control subjects, and 2) the effect of acute β2AR agonist inhalation on lung fluid balance. Methods: Twenty-two stable HFrEF patients and 18 age- and sex-matched healthy subjects were studied. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary conductance (DmCO), pulmonary capillary blood volume (Vc) (via rebreathe) and lung tissue volume (Vtis) (via computed tomography) were assessed before and within 30 min of administration of nebulized albuterol. EVLW was derived as Vtis – Vc. Results: Pre-albuterol, Vtis and EVLW were greater in HFrEF vs. control (998 ± 200 vs. 884 ± 123 ml, P = 0.041; 943 ± 202 vs. 802 ± 133 ml, P = 0.015, respectively). Albuterol decreased Vtis and EVLW in HFrEF (−4.6 ± 7.8%, P = 0.010; −4.6 ± 8.8%, P = 0.018) and control (−2.8 ± 4.9%, P = 0.029; −3.0 ± 5.7%, P = 0.045). There was an inverse relationship between pre-albuterol values and the pre- to post-albuterol change for EVLW (r2 = −0.264, P = 0.015) and DmCO (r2 = −0.343, P = 0.004) in HFrEF only. Conclusion: Lung fluid is elevated in stable HFrEF patients relative to healthy subjects. Stimulation of the β2ARs may cause fluid removal in HFrEF, especially in patients who exhibit greater evidence for increased lung water at baseline