Targeted metagenomics reveals pangenomic diversity of the nitroplast (UCYN-A) and its algal host plastid.

UCYN-A (Cand. Atelocyanobacterium thalassa) has recently been recognized as a globally-distributed, early stage, nitrogen-fixing organelle (the 'nitroplast') of cyanobacterial origin present in select species of haptophyte algae (e.g., Braarudosphaera bigelowii). Although the nitroplast was recognized as the UCYN-A2 sublineage, it is yet to be confirmed in other sublineages of the algal/UCYN-A complex. We used water samples collected from Halifax Harbour (Bedford Basin, Nova Scotia, Canada) and the offshore Scotian Shelf to further our understanding of B. bigelowii and UCYN-A in the coastal Northwest Atlantic. Sequencing data revealed UCYN-A-associated haptophyte signatures and yielded near-complete metagenome-assembled genomes (MAGs) for UCYN-A1, UCYN-A4, and the plastid of the A4-associated haptophyte. Comparative genomics provided new insights into the pangenome of UCYN-A. The UCYN-A4 MAG is the first genome sequenced from this sublineage and shares ~85% identity with the UCYN-A2 nitroplast. Genes missing in the reduced genome of the nitroplast were also missing in the A4 MAG supporting its likely classification as a nitroplast as well. The UCYN-A1 MAG was found to be nearly 100% identical to the reference genome despite coming from different ocean basins. Time-series data paired with the recurrence of specific microbes in enrichment cultures gave insight into the microbes that frequently co-occur with the algal/UCYN-A complex (e.g., Pelagibacter ubique). Overall, our study expands knowledge of UCYN-A and its host across major ocean basins and investigates their co-occurring microbes in the coastal Northwest Atlantic (NWA), thereby facilitating future studies on the underpinnings of haptophyte-associated diazotrophy in the sea.

Activation and functionalisation of carbon dioxide by bis-tris(pyrazolyl)borate-supported divalent samarium and trivalent lanthanide silylamide complexes.

Synthesis and reactivity with carbon dioxide (CO2) of divalent samarium in the bis-tris(pyrazolyl)borate ligand environment has been reported. In addition, CO2 activation and functionalisation by lanthanide silylamides in the bis-tris(pyrazolyl)borate ligand environment was demonstrated. Reduction of the Sm(III) precursor [Sm(Tp)2(OTf)] (Tp = hydrotris(1-pyrazolyl)borate; OTf = triflate) with KC8 yielded the insoluble Sm(II) multi-metallic coordination polymer [{Sm(Tp)2}n] 1-Sm. Addition of 1,2-dimethoxyethane (DME) to 1-Sm enabled isolation of the monomeric complex [Sm(Tp)2(DME)] 1-Sm(DME). Complex 1-Sm(DME) reduced CO2 to yield the oxalate-bridged dimeric Sm(III) complex [{Sm(Tp)2}2(µ-η2:η2-O2CCO2)] 2-Sm. The reactions of heteroleptic Ln(III) silylamide complexes [Ln(Tp)2(N'')] (Ln = Y, Sm; N'' = N(SiMe3)2) with CO2 yielded monomeric Ln(III) silyloxides [Ln(Tp)2(OSiMe3)] 3-Ln and trimethylsilyl isocyanate (OCNSiMe3). Complexes 3-Ln are the first crystallographically characterised examples of Ln(III)-OSiMe3 bonds accessed via CO2 activation and functionalisation. Full characterisation data are presented for all complexes, including solid-state molecular structure determination by single-crystal X-ray diffraction.

Citric acid cross-linked pomegranate peel extract-loaded pH-responsive ß-cyclodextrin/carboxymethyl tapioca starch hydrogel film for diabetic wound healing.

Pomegranate peel extract (PPE) hydrogel films filled with citric acid (CA) and ß-cyclodextrin-carboxymethyl tapioca starch (CMS) were designed mainly to prevent wound infections and speed up the healing process. FTIR and NMR studies corroborated the carboxymethylation of neat tapioca starch (NS). CMS exhibited superior swelling behavior than NS. The amount of CA and ß-CD controlled the physicochemical parameters of developed PPE/CA/ß-CD/CMS films. Optimized film (OF) exhibited acceptable swellability, wound fluid absorptivity, water vapor transmission rate, water contact angle, and mechanical properties. Biodegradable, biocompatible, and antibacterial films exhibited pH dependence in the release of ellagic acid for up to 24 h. In mice model, PPE/CA/ß-CD/CMS hydrogel film treatment showed promising wound healing effects, including increased collagen deposition, reduced inflammation, activation of the Wingless-related integration site (wnt) pathway leading to cell division, proliferation, and migration to the wound site. The expression of the WNT3A gene did not show any significant differences among all the studied groups. Developed PPE-loaded CA/ß-CD/CMS film promoted wound healing by epithelialization, granulation tissue thickness, collagen deposition, and angiogenesis, hence could be recommended as a biodegradable and antibacterial hydrogel platform to improve the cell proliferation during the healing of diabetic wounds.

Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice.

Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.

Synthesis and Reactivity of Bis-tris(pyrazolyl)borate Lanthanide/Aluminum Heterobimetallic Trihydride Complexes.

Molecular heterobimetallic hydride complexes of lanthanide (Ln) and main-group (MG) metals exhibit chemical properties unique from their monometallic counterparts and are highly reactive species, making their synthesis and isolation challenging. Herein, molecular Ln/Al heterobimetallic trihydrides [Ln(Tp)2(µ-H)2Al(H)(N″)] [2-Ln; Ln = Y, Sm, Dy, Yb; Tp = hydrotris(1-pyrazolyl)borate; N″ = N(SiMe3)2] have been synthesized by facile insertion of aminoalane [Me3N·AlH3] into the Ln-N amide bonds of [Ln(Tp)2(N″)] (1-Ln). Thus, this is a simple synthetic strategy to access a range of Ln/Al hydrides. Reactivity studies demonstrate that 2-Ln is a heterobimetallic hydride, with evidence for the cooperative nature of 2-Ln shown by the catalytic amine-borane dehydrocoupling under ambient conditions in contrast to its monomeric counterparts.

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit.

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Advancing Virtual at-Home Care for Community Health Center Patients Using Patient Self-Care Tools, Technology, and Education.

Introduction: Health centers are community-based, patient directed primary care providers that offer accessible, high-quality primary care within medically underserved communities. Screening for cancer and managing complex chronic conditions such as diabetes, hypertension, obesity, and depression are vital services for the vulnerable populations seen by community health centers. Delivering care for complex chronic conditions and preventive services using virtual models that integrate self-care tools and technology is an important approach to increasing access for hard-to-reach patients served by health centers. Objective: This study aimed to explore the use of a virtual care model, applied using a systems approach and patient-driven tools and technology, on the performance of clinical and patient experience measures. Methods: A virtual care model, applied using a systems approach offered by the Value Transformation Framework (VTF), was combined with self-care tools and technology in twenty health centers across 17 states to drive improvement efforts. Changes in clinical measures and patient experience were compared. Results: A total of 385 patients were enrolled and 270 (70.1%) completed a baseline visit and at least four virtual visits during the six-month intervention period. Statistically significant improvements were seen in measures for HbA1c, systolic and diastolic blood pressure, and bodyweight. Among the 270 who completed the baseline and at least 4 virtual visits, the percentage up-to-date for colorectal cancer screening increased from 113/270 (41.9%) to 169/270 (62.6%) after six months, p<0.001, a 20.7% increase. Patients completing the baseline visit and at least 4 virtual visits reported a 10.7% decrease in depression and increased satisfaction with virtual care visits compared to in-person visits (p<0.001). Conclusion: Health centers applying the Value Transformation Framework's organizing framework to the use of virtual care models together with patient self-care tools, technology, and education, had improvements in measures for chronic and preventive conditions and patient experience.

Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: shared neuronal mechanisms?

Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent preclinical experimental data in rodents, we provide a coherent and unifying neurobiological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.

Self-Measured Blood Pressure Monitoring During the COVID-19 Pandemic: Perspectives From Community Health Center Clinicians.

ABSTRACT: The early period of the COVID-19 pandemic necessitated a rapid increase in out-of-office care. To capture the impact from COVID-19 on care for patients with hypertension, a questionnaire was disseminated to community health center clinicians. The extent, types, and causes of care delays and disruptions were assessed along with adaptations and innovations used to address them. Clinician attitudinal changes and perspectives on future hypertension care were also assessed. Of the 65 respondents, most (90.8%) reported their patients with hypertension experienced care delays or disruptions, including lack of follow-up, lack of blood pressure assessment, and missed medication refills or orders. To address care delays and disruptions for patients with hypertension, respondents indicated that their health center increased the use of telehealth or other technology, made home blood pressure devices available to patients, expanded outreach and care coordination, provided medication refills for longer periods of time, and used new care delivery options. The use of self-measured blood pressure monitoring (58.5%) and telehealth (43.1%) was identified as the top adaptations that should be sustained to increase access to and patient engagement with hypertension care; however, barriers to both remain. Policy and system level changes are needed to support value-based care models that include self-measured blood pressure and telehealth.

Therapeutically targeting type I interferon directly to XCR1+ dendritic cells reveals the role of cDC1s in anti-drug antibodies.

Conventional type 1 dendritic cells (cDC1s) are superior in antigen cross-presentation and priming CD8+ T cell anti-tumor immunity and thus, are a target of high interest for cancer immunotherapy. Type I interferon (IFN) is a potent inducer of antigen cross-presentation, but, unfortunately, shows only modest results in the clinic given the short half-life and high toxicity of current type I IFN therapies, which limit IFN exposure in the tumor. CD8+ T cell immunity is dependent on IFN signaling in cDC1s and preclinical studies suggest targeting IFN directly to cDC1s may be sufficient to drive anti-tumor immunity. Here, we engineered an anti-XCR1 antibody (Ab) and IFN mutein (IFNmut) fusion protein (XCR1Ab-IFNmut) to determine whether systemic delivery could drive selective and sustained type I IFN signaling in cDC1s leading to anti-tumor activity and, in parallel, reduced systemic toxicity. We found that the XCR1Ab-IFNmut fusion specifically enhanced cDC1 activation in the tumor and spleen compared to an untargeted control IFN. However, multiple treatments with the XCR1Ab-IFNmut fusion resulted in robust anti-drug antibodies (ADA) and loss of drug exposure. Using other cDC1-targeting Ab-IFNmut fusions, we found that localizing IFN directly to cDC1s activates their ability to promote ADA responses, regardless of the cDC1 targeting antigen. The development of ADA remains a major hurdle in immunotherapy drug development and the cellular and molecular mechanisms governing the development of ADA responses in humans is not well understood. Our results reveal a role of cDC1s in ADA generation and highlight the potential ADA challenges with targeting immunostimulatory agents to this cellular compartment.

A Second Glass Transition Observed in Single-Component Homogeneous Liquids Due to Intramolecular Vitrification.

On supercooling a liquid, the viscosity rises rapidly until at the glass transition it vitrifies into an amorphous solid accompanied by a steep drop in the heat capacity. Therefore, a pure homogeneous liquid is not expected to display more than one glass transition. Here we show that a family of single-component homogeneous molecular liquids, titanium tetraalkoxides, exhibit two calorimetric glass transitions of comparable magnitude, one of which is the conventional glass transition associated with dynamic arrest of the bulk liquid properties, while the other is associated with the freezing out of intramolecular degrees of freedom. Such intramolecular vitrification is likely to be found in molecules in which low-frequency terahertz intramolecular motion is coupled to the surrounding liquid. These results imply that intramolecular barrier-crossing processes, typically associated with chemical reactivity, do not necessarily follow the Arrhenius law but may freeze out at a finite temperature.

Design and Synthesis of Novel Fluorescent 2-(aryloxy)-3-(4,5-diaryl)-1H-imidazol-2-yl)quinolines: Solvatochromic, DFT, TD-DFT Studies, COX-1 and COX-2 Inhibition and Antioxidant Properties.

The present work focuses on the synthesis of novel heterocycles 2-(aryloxy)-3-(4,5-diaryl-1H-imidazol-2-yl)quinolines (6k-v) by an effective condensation reaction. These molecules exhibited fluorescent properties and hence for the proper understanding of their optical behavior and quantum yields, solvatochromic studies have been carried out. Further, frontier molecular orbitals, molecular electrostatic potential (MEP), and geometrical structure optimization have been investigated using the B3LYP/6-311G ++ (d, p) method. The energy gap between the HOMO, LUMO of the optical and energy band gap is determined by DFT and UV-visible spectra for TD-DFT studies are done. The screening of these compounds for in vitro COX-1 and COX-2 inhibition and DPPH free radical scavenging ability assays produced promising results. The binding interactions of these molecules against the COX-2 enzyme (PDB: 5IKR) were validated by docking studies.

Manilkara zapota L. extract topical ointment application to skin wounds in rats speeds up the healing process.

Poor circulation, unresolved inflammation, neuropathy, and infection make wound care difficult. Manilkara zapota (M. zapota) antibacterial and antioxidant properties may help speed up the healing process. The present investigation aimed to evaluate the wound healing activity of M. zapota bark ethanolic extract (MZE) by employing in-vitro migration scratch assay and in-vivo animal models. Wistar albino rats were used for the in-vivo wound healing models. No treatment was given to Group I; Group II received povidone-iodine (5% W/W); Group III received MZE (5% W/W); and Group IV received MZE (10% W/W). Linear incision models and excision wound models were used to induce injury. The ointments were applied immediately to the wounds after causing the injury. The percentage of wound contraction, the length of the epithelization period, and the wound's tensile strength were all calculated. The scratch assay assessed the test drug's potential for wound healing in-vitro. H2O2 and DPPH scavenging assays were used to measure antioxidant activity. A p < 0.05 was used to define statistical significance. On days 4, 8, 12, 16, and 20, the wound contraction potential of animals treated with MZE ointment was significantly higher (p < 0.001) than that of the control group. On day 20, the proportion of wound contraction in MZE-treated animals was 99.88%, compared to 83.86% in untreated animals. The test group had a significantly (p < 0.01) faster time to full epithelization than the control group. In the incision model, the control group had considerably lower mechanical strength (p < 0.001) than animals treated with MZE. In addition, MZE caused a significant increase (p < 0.001) in total protein and hydroxyproline levels. In the scratch experiment, test drug-treated cells showed a higher rate of cell migration than untreated cells. Furthermore, animals treated with MZE showed increased levels of epithelial tissue, collagen proliferation, and keratinization. To summarize, the current study found that M. zapota improved wound healing activity both in vitro and in vivo, as evidenced by the study results. M. zapota extract has significant wound-healing potential and could be a viable source of wound-healing nutraceuticals.

Novel jointured green synthesis of chitosan­silver nanocomposite: An approach towards reduction of nitroarenes, anti-proliferative, wound healing and antioxidant applications.

Here we present the simple green synthesis of chitosan­silver nanocomposite (CS-Ag NC) by employing kiwi fruit juice as reducing agent. The structure, morphology, and composition of CS-Ag NC were determined using characterization techniques such as XRD, SEM-EDX, UV-visible, FT-IR, particle size, and zeta potential. The prepared CS-Ag nanocomposite was effectively used as catalyst in the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 as reductant, in aqueous medium at room temperature. The toxicity of CS-Ag NC was assessed on Normal (L929) cell line, Lung cancer (A549) cell line and Oral cancer (KB-3-1) cell line and their respective IC50values observed were 83.52 µg/mL, 66.74 µg/mL and 75.11 µg/mL. The CS-Ag NC displayed significant cytotoxic activity and the cell viability percentage for normal, lung and oral cancer cell lines were found to be 42.87 ± 0.0060, 31.28 ± 0.0045 and 35.90 ± 0.0065 respectively. Stronger cell migration was exemplified by CS-Ag NC and the percentage of wound closure (97.92%) was substantially identical to that of the standard drug ascorbic acid (99.27%). Further CS-Ag nanocomposite was subjected for in vitro antioxidant activity.

Athletic Trainers' Perceptions of and Experience with Social Determinants of Health.

The role that social determinants of health (SDHs) play in athletic healthcare is gaining attention, yet little is known about athletic trainers' (ATs) perceptions of and encounters with the impact of SDHs. The purpose of this study was to evaluate ATs' perceptions of various SDHs and their experience treating patients whose health and well-being were influenced by SDHs. This was a cross-sectional, web-based survey completed by 1694 ATs (completion rate = 92.6%; 61.1% female; age = 36.6 ± 10.8 years). The survey consisted of several multipart questions focusing on specific SDHs. Descriptive statistics were used to report frequencies and percentages. Results indicated widespread agreement that SDHs matter to patient health and are of concern in athletic healthcare. The SDHs that ATs most commonly reported encountering included lifestyle choices (n = 1306/1406; 93.0%), social support (n = 1185/1427; 83.0%), income (n = 1167/1502; 77.7%), and access to quality and timely healthcare (n = 1093/1420, 77.0%). The SDHs that ATs least commonly reported having experience with was governmental policy (n = 684/1411; 48%). The perceived importance of SDHs among ATs and their commonly reported experiences managing patient cases in which SDHs negatively influence patients' health and healthcare suggest that efforts to assess these factors are needed so that strategies to address their influence on athletic healthcare can be identified.

Outcomes and Adverse Effects of Baricitinib Versus Tocilizumab in the Management of Severe COVID-19.

OBJECTIVES: The National Institutes of Health and Infectious Diseases Society of America guidelines recommend tocilizumab or baricitinib in the management of severe COVID-19. Despite clinical trials on the individual agents, there are no large-scale studies comparing the two agents to guide the selection of one versus the other. The purpose of this study was to compare the outcomes and adverse effects of baricitinib versus tocilizumab in the management of severe COVID-19. DESIGN: Retrospective, observational cohort study. SETTING: Eleven acute care hospitals in a large health system in Georgia. PATIENTS: Adult patients with severe COVID-19 who received at least one dose of either baricitinib or tocilizumab between June 2021 and October 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. The key secondary outcome was occurrence rate of adverse effects. A total of 956 patients were identified. The median age was 57 years, and 53% were of male sex. The median body mass index was 33.5, and more than 94% of the population was unvaccinated. Propensity score matching by baseline characteristics resulted in a total of 582 patients, 291 in each group. There was no difference in mortality between the two groups; however, the occurrence rate of adverse effects was significantly higher in the tocilizumab group compared with baricitinib: secondary infections (32% vs 22%; p < 0.01); thrombotic events (24% vs 16%; p < 0.01); and acute liver injury (8% vs 3%; p < 0.01). CONCLUSIONS: Our propensity score-matched, retrospective, observational study in patients hospitalized with severe COVID-19 showed no difference in mortality but significantly fewer adverse effects with baricitinib compared with tocilizumab. Our data suggest that baricitinib may be a better choice when treating patients with severe COVID-19, but additional prospective, randomized trials are needed to help clinicians choose the most optimal drug.

Reduction chemistry yields stable and soluble divalent lanthanide tris(pyrazolyl)borate complexes.

Reduction of the heteroleptic Ln(III) precursors [Ln(Tp)2(OTf)] (Tp = hydrotris(1-pyrazolyl)borate; OTf = triflate) with either an aluminyl(I) anion or KC8 yielded the adduct-free homoleptic Ln(II) complexes dimeric 1-Eu [{Eu(Tp)(µ-κ1:η5-Tp)}2] and monomeric 1-Yb [Yb(Tp)2]. Complexes 1-Ln have good solubility and stability in both non-coordinating and coordinating solvents. Reaction of 1-Ln with 2 Ph3PO yielded 1-Ln(OPPh3)2. All complexes are intensely coloured and 1-Eu is photoluminescent. The electronic absorption data show the 4f-5d electronic transitions in Ln(II). Single-crystal X-ray diffraction data reveal first µ-κ1:η5-coordination mode of the unsubstituted Tp ligand to lanthanides in 1-Eu.

The Primary Care Transformation Executive Fellowship to Develop Community Health Center Leaders.

Introduction: Although many primary care providers from community health centers recognize health disparities and work to transform healthcare, skill gaps and limited support may hinder their ability to be change agents. The Primary Care Transformation Executive (PCTE) Fellowship at A.T. Still University School of Osteopathic Medicine in Arizona (ATSU-SOMA) seeks to address these barriers by providing professional development and support to primary care providers interested in leading change in the nation's health centers. Methods: The PCTE Fellowship is a structured, one-year interprofessional learning experience that emphasizes topics such as healthcare transformation, interprofessional practice, leadership development, and systems thinking. Quantitative and qualitative evaluation of the program was accomplished through surveys and semi-structured interviews throughout the fellowship. Results: Feedback from 18 fellows showed perceived improvements in knowledge and skills related to the various curricular topics, increased engagement in leadership activities, and career advancement. Fellows developed practice and quality improvement projects and successfully implemented the projects within their health systems, addressing observed disparities. Conclusion: Professional development and directed support for primary care providers can enhance their engagement in healthcare transformation and advance health equity.

Using the Practical Robust Implementation and Sustainability Model (PRISM) to Identify and Address Provider-Perceived Barriers to Optimal Statin Prescribing and Use in Community Health Centers.

Statins are an important but underutilized therapy to prevent cardiovascular events, particularly in high-risk patients. To increase use of statin therapy in high-risk patients, the Centers for Disease Control and Prevention funded a project led by the National Association of Community Health Centers to discover reasons for statin underuse in health centers and identify possible leverage points, particularly among vulnerable and underserved patients. The project further sought to develop training and educational materials to improve statin prescribing for and acceptance in eligible high-risk patients. As a first step, investigators implemented a questionnaire to clinical providers (n = 45) at health centers participating in the project to obtain their perspective on barriers to optimal statin use. We used the practical robust implementation and sustainability model (PRISM) domains to frame the overall project and guide the development of our questionnaire. This paper summarizes top perceived barriers to patient and health system/provider statin initiation and sustainment, as well as facilitators to prescribing, using PRISM as an organizing framework. Our questionnaire yielded important suggestions related to public awareness, education materials, health information technology (HIT)/data solutions, and clinical guidelines as key factors in optimizing statin use. It also informed the design of patient education resources and provider training tools. Future directions include using the full application of the PRISM implementation science model to assess how well our educational and training resources help overcome barriers to statin use in high-risk patients, including evaluating how key contextual factors influence successful implementation.