Healthy Valleys : reversing decline in eight rural communities

Healthy Valleys is a community focused health improvement initiative and our operating principles are our strength – we adopt a community development approach, we are flexible, responsive to communities, effective and innovative. Healthy Valleys adds value when delivering services because we are effective at engaging with disadvantaged communities. Indeed Healthy Valleys engages local people and delivers services in local places, all of which contribute to making a positive difference

Nonsolar astronomy with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI)

The Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) is a NASA Small Explorer satellite designed to study hard x-ray and gamma-ray emission from solar flares. In addition, its high-resolution array of germanium detectors can see photons from high-energy sources throughout the Universe. Here we discuss the various algorithms necessary to extract spectra, lightcurves, and other information about cosmic gamma-ray bursts, pulsars, and other astrophysical phenomena using an unpointed, spinning array of detectors. We show some preliminary results and discuss our plans for future analyses. All RHESSI data are public, and scientists interested in participating should contact the principal author

In vitro evaluation of bi-layer silk fibroin scaffolds for gastrointestinal tissue engineering

Silk fibroin scaffolds were investigated for their ability to support attachment, proliferation, and differentiation of human gastrointestinal epithelial and smooth muscle cell lines in order to ascertain their potential for tissue engineering. A bi-layer silk fibroin matrix composed of a porous silk fibroin foam annealed to a homogeneous silk fibroin film was evaluated in parallel with small intestinal submucosa scaffolds. AlamarBlue analysis revealed that silk fibroin scaffolds supported significantly higher levels of small intestinal smooth muscle cell, colon smooth muscle cell, and esophageal smooth muscle cell attachment in comparison to small intestinal submucosa. Following 7 days of culture, relative numbers of each smooth muscle cell population maintained on both scaffold groups were significantly elevated over respective 1-day levels—indicative of cell proliferation. Real-time reverse transcription polymerase chain reaction and immunohistochemical analyses demonstrated that both silk fibroin and small intestinal submucosa scaffolds were permissive for contractile differentiation of small intestinal smooth muscle cell, colon smooth muscle cell, esophageal smooth muscle cell as determined by significant upregulation of α-smooth muscle actin and SM22α messenger RNA and protein expression levels following transforming growth factor-β1 stimulation. AlamarBlue analysis demonstrated that both matrix groups supported similar degrees of attachment and proliferation of gastrointestinal epithelial cell lines including colonic T84 cells and esophageal epithelial cells. Following 14 days of culture on both matrices, spontaneous differentiation of T84 cells toward an enterocyte lineage was confirmed by expression of brush border enzymes, lactase, and maltase, as determined by real-time reverse transcription polymerase chain reaction and immunohistochemical analyses. In contrast to small intestinal submucosa scaffolds, silk fibroin scaffolds supported spontaneous differentiation of esophageal epithelial cells toward a suprabasal cell lineage as indicated by significant upregulation of cytokeratin 4 and cytokeratin 13 messenger RNA transcript levels. In addition, esophageal epithelial cells maintained on silk fibroin scaffolds also produced significantly higher involucrin messenger RNA transcript levels in comparison to small intestinal submucosa counterparts, indicating an increased propensity for superficial, squamous cell specification. Collectively, these data provide evidence for the potential of silk fibroin scaffolds for gastrointestinal tissue engineering applications

Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

BackgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.MethodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.ResultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.ConclusionsAV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD

Rural Health Clinic Readiness for Patient-Centered Medical Home Recognition: Preparing for the Evolving Healthcare Marketplace [Policy Brief]

The patient-centered medical home (PCMH) model reaffirms traditional primary care values including continuity of care, connection with an identified personal clinician, provision of same day- and after-hours access, and positions providers to participate in accountable care and other financing and delivery system models. However, little is known about the readiness of the over 4,000 Rural Health Clinics (RHCs) to meet the PCMH Recognition standards established by the National Council for Quality Assurance (NCQA). The authors present findings from a survey of RHCs that examined their capacity to meet the NCQA PCMH requirements, and discuss the implications of the findings for efforts to support RHC capacity development. Key Findings: Based on their performance on the “must pass” elements and related key factors, Rural Health Clinics (RHCs) are likely to have difficulties gaining National Center for Quality Assurance’s (NCQA) Patient-Centered Medical Home (PCMH) Recognition. RHCs perform best on standards related to recording demographic information and managing clinical activities, particularly for those using an electronic health record. RHCs perform less well on improving access to and continuity of services, supporting patient self-management skills and shared decision-making, implementing continuous quality improvement systems, and building practice teams. RHCs are likely to need substantial technical assistance targeting clinical and operational performance to gain NCQA PCMH Recognition

Pilot testing a Rural Health Clinic quality measurement reporting system

More than 4,000 Rural Health Clinics (RHCs) serve the primary care needs of rural communities, and are therefore an important source of primary care and other essential health services for rural residents. Unfortunately, the Rural Health Clinic Program is plagued by a lack of data on the financial, operational, and quality performance of participating clinics. In light of the significant expansion of quality performance reporting and growing use of performance-based payment approaches, it is critically important that RHCs be able to compete in this changing healthcare market. To this end, we piloted the reporting and use of a small set of primary care-relevant quality measures by a geographically diverse sample of RHCs. This policy brief reports on the results of this pilot with a focus on assessing the feasibility and utility of the reporting system and quality measures for the participating RHCs

Biopolymeric Nanoparticle Synthesis in Ionic Liquids

Recently, much research has focused on the use of biopolymers, which are regarded as biodegradable, natural, and environmentally friendly materials. In this context, biopolymeric nanoparticles have attracted great attention in the last few years due to their multiple applications especially in the field of biomedicine. Ionic liquids have emerged as promising solvents for use in a wide variety of chemical and biochemical processes for their extraordinary properties, which include negligible vapor pressure, high thermal and chemical stability, lower toxicity than conventional organic solvents, and the possibility of tuning their physical–chemical properties by choosing the appropriate cation and anion. We here review the published works concerning the synthesis of biopolymeric nanoparticles using ionic liquids, such as trimethylsilyl cellulose or silk fibroin. We also mention our recent studies describing how high-power ultrasounds are capable of enhancing the dissolution process of silk proteins in ionic liquids and how silk fibroin nanoparticles can be directly obtained from the silk fibroin/ionic liquid solution by rapid desolvation in polar organic solvents. As an example, their potential biomedical application of curcumin-loaded silk fibroin nanoparticles for cancer therapy is also discussed

Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases

Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non‐native polyketide substrates. Reactions pairing wildtype PKS modules with non‐native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non‐cognate TE domains was severely reduced. In contrast, non‐native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wild‐type polyketide synthases with non‐native substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of non‐native substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/2/ange202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/1/ange202004991.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/3/ange202004991_am.pd