Increasing the antioxidant capacity of ceria nanoparticles with catechol-grafted poly(ethylene glycol).

Ceria nanoparticles are remarkable antioxidants due to their large cerium(III) content and the possibility of recovering cerium(III) from cerium(IV) after reaction. Here we increase the cerium(III) content of colloidally stable nanoparticles (e.g., nanocrystals) using a reactive polymeric surface coating. Catechol-grafted poly(ethylene glycols) (PEG) polymers of varying lengths and architectures yield materials that are non-aggregating in a variety of aqueous media. Cerium(IV) on the ceria surface both binds and oxidizes the catechol functionality, generating a dark-red colour emblematic of surface-oxidized catechols with a concomitant increase in cerium(III) revealed by X-ray photoemission spectroscopy (XPS). The extent of ceria reduction depends sensitively on the architecture of the coating polymer; small and compact polymer chains pack with high density at the nanoparticle surface yielding the most cerium(III). Nanoparticles with increased surface reduction, quantified by the intensity of their optical absorption and thermogravimetric measures of polymer grafting densities, were more potent antioxidants as measured by a standard TEAC antioxidant assay. For the same core composition nanoparticle antioxidant capacities could be increased over an order of magnitude by tailoring the length and architecture of the reactive surface coatings.

Remodeling the Medication Collection Process With Prescription in Locker Box (PILBOX): Prospective Cross-sectional Study.

BACKGROUND: Traditionally, patients wishing to obtain their prescription medications have had to physically go to pharmacy counters and collect their medications via face-to-face interactions with pharmacy staff. Prescription in Locker Box (PILBOX) is a new innovation allowing patients and their caregivers to collect medication asynchronously, 24/7 at their convenience, from medication lockers instead of from pharmacy staff. OBJECTIVE: This study aimed to determine the willingness of patients and caregivers to use this new innovation and factors that affect their willingness. METHODS: This prospective cross-sectional study was conducted over 2 months at 2 public primary health care centers in Singapore. Patients or caregivers aged 21 years and older who came to pharmacies to collect medications were administered a 3-part questionnaire face-to-face by trained study team members after they gave their consent to participate in the study. RESULTS: A total of 222 participants completed the study. About 40% (89/222, 40.1%) of participants were willing to use PILBOX to collect their medications. Among participants who were keen to use the PILBOX service, slightly more than half (47/89, 53%) were willing to pay for the PILBOX service. Participants felt that ease of use (3.5 [SD 1.2]) of PILBOX was the most important factor affecting their willingness to use the medication pickup service. This was followed by waiting time (3.4 [SD 1.3]), cost of using the medication pickup service (3.0 [SD 1.4]), and 24/7 accessibility (2.6 [SD 1.4]). This study also found that age (P=.01), language literacy (P<.001), education level (P<.001), working status (P=.01), and personal monthly income (P=.01) were factors affecting the willingness of patients or caregivers to use PILBOX. CONCLUSIONS: Patients and caregivers are keen to use PILBOX to collect their medications for its convenience and the opportunity to save time if it is easy to use and not costly.

A 3Din vitromodel of the device-tissue interface: functional and structural symptoms of innate neuroinflammation are mitigated by antioxidant ceria nanoparticles.

Objective.The recording instability of neural implants due to neuroinflammation at the device-tissue interface is a primary roadblock to broad adoption of brain-machine interfaces. While a multiphasic immune response, marked by glial scaring, oxidative stress (OS), and neurodegeneration, is well-characterized, the independent contributions of systemic and local 'innate' immune responses are not well-understood. We aimed to understand and mitigate the isolated the innate neuroinflammatory response to devices.Approach.Three-dimensional primary neural cultures provide a unique environment for studying the drivers of neuroinflammation by decoupling the innate and systemic immune systems, while conserving an endogenous extracellular matrix and structural and functional network complexity. We created a three-dimensionalin vitromodel of the device-tissue interface by seeding primary cortical cells around microwires. Live imaging of both dye and Adeno-Associated Virus (AAV) - mediated functional, structural, and lipid peroxidation fluorescence was employed to characterize the neuroinflammatory response.Main results.Live imaging of microtissues over time revealed independent innate neuroinflammation, marked by increased OS, decreased neuronal density, and increased functional connectivity. We demonstrated the use of this model for therapeutic screening by directly applying drugs to neural tissue, bypassing low bioavailability through thein vivoblood brain barrier. As there is growing interest in long-acting antioxidant therapies, we tested efficacy of 'perpetual' antioxidant ceria nanoparticles, which reduced OS, increased neuronal density, and protected functional connectivity.Significance.Our three-dimensionalin vitromodel of the device-tissue interface exhibited symptoms of OS-mediated innate neuroinflammation, indicating a significant local immune response to devices. The dysregulation of functional connectivity of microcircuits surround implants suggests the presence of an observer effect, in which the process of recording neural activity may fundamentally change the neural signal. Finally, the demonstration of antioxidant ceria nanoparticle treatment exhibited substantial promise as a neuroprotective and anti-inflammatory treatment strategy.

The cost of improving care: a multisite economic analysis of hospital resource use for implementing recommended postpartum contraception programmes.

BACKGROUND: The costs of quality improvement efforts in real-world settings are often unquantified. Better understanding could guide appropriate resource utilisation and drive efficiency. Immediate postpartum contraceptive care (ie, placement of an intrauterine device or contraceptive implant during hospitalisation for childbirth) represents an excellent case study for examining costs, because recommended services are largely unavailable and adoption requires significant effort. We therefore evaluated the cost of implementing immediate postpartum contraceptive services at four academic centres and one private hospital in USA. METHODS: In this mixed-methods cost analysis, implementation activities were retrospectively identified using standardised data collection. Activities were categorised as preimplementation activities (infrastructure building, tool creation and stakeholder engagement) or execution activities (workforce training and process refinement). Costs were assigned based on national median salaries for the roles of individuals involved. Cross-case comparison and rapid qualitative analysis guided by the Consolidated Framework for Implementation Research were used to identify factors driving cost variation observed across sites. RESULTS: On average, implementation activities required 204 hours (range 119-368), with this time costing $14 433.94 (range $9955.61-$23 690.49), and involving 9 (range 7-11) key team members per site. Preimplementation activities required more resources than execution activities (preimplementation: average 173 hours, $11 573.25; execution: average 31 hours, $2860.67). Sites that used lower-cost employees (eg, shifting tasks from a physician to a project manager) observed lower costs per hour for implementation activities. Implementation activities and costs were associated with local contextual factors, including stakeholder acceptance, integration of employees and infrastructure readiness for the change effort. CONCLUSIONS: Our findings provide the first estimates of health system costs for adopting recommended contraceptive care in maternity units in USA. More broadly, our findings suggest that the budget impact of improvement efforts may vary widely depending on local context.

Stem cell antigen-1 in skeletal muscle function.

Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age.

Concise review: stem cell therapy for muscular dystrophies.

Muscular dystrophy comprises a group of genetic diseases that cause progressive weakness and degeneration of skeletal muscle resulting from defective proteins critical to muscle structure and function. This leads to premature exhaustion of the muscle stem cell pool that maintains muscle integrity during normal use and exercise. Stem cell therapy holds promise as a treatment for muscular dystrophy by providing cells that can both deliver functional muscle proteins and replenish the stem cell pool. Here, we review the current state of research on myogenic stem cells and identify the important challenges that must be addressed as stem cell therapy is brought to the clinic.

miR-125b promotes early germ layer specification through Lin28/let-7d and preferential differentiation of mesoderm in human embryonic stem cells.

Unlike other essential organs, the heart does not undergo tissue repair following injury. Human embryonic stem cells (hESCs) grow indefinitely in culture while maintaining the ability to differentiate into many tissues of the body. As such, they provide a unique opportunity to explore the mechanisms that control human tissue development, as well as treat diseases characterized by tissue loss, including heart failure. MicroRNAs are small, non-coding RNAs that are known to play critical roles in the regulation of gene expression. We profiled the expression of microRNAs during hESC differentiation into myocardial precursors and cardiomyocytes (CMs), and determined clusters of human microRNAs that are specifically regulated during this process. We determined that miR-125b overexpression results in upregulation of the early cardiac transcription factors, GATA4 and Nkx2-5, and accelerated progression of hESC-derived myocardial precursors to an embryonic CM phenotype. We used an in silico approach to identify Lin28 as a target of miR-125b, and validated this interaction using miR-125b knockdown. Anti-miR-125b inhibitor experiments also showed that miR-125b controls the expression of miRNA let-7d, likely through the negative regulatory effects of Lin28 on let-7. We then determined that miR-125b overexpression inhibits the expression of Nanog and Oct4 and promotes the onset of Brachyury expression, suggesting that miR-125b controls the early events of human CM differentiation by inhibiting hESC pluripotency and promoting mesodermal differentiation. These studies identified miR-125b as an important regulator of hESC differentiation in general, and the development of hESC-derived mesoderm and cardiac muscle in particular. Manipulation of miR-125b-mediated pathways may provide a novel approach to directing the differentiation of hESC-derived CMs for cell therapy applications.