Open-Label Sulforaphane Trial in FMR1 Premutation Carriers with Fragile-X-Associated Tremor and Ataxia Syndrome (FXTAS).

Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60-88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.

Intranasal neuropeptide Y1 receptor antagonism improves motor deficits in symptomatic SOD1 ALS mice.

OBJECTIVE: Neuropeptide Y (NPY) is a 36 amino acid peptide widely considered to provide neuroprotection in a range of neurodegenerative diseases. In the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), recent evidence supports a link between NPY and ALS disease processes. The goal of this study was to determine the therapeutic potential and role of NPY in ALS, harnessing the brain-targeted intranasal delivery of the peptide, previously utilised to correct motor and cognitive phenotypes in other neurological conditions. METHODS: To confirm the association with clinical disease characteristics, NPY expression was quantified in post-mortem motor cortex tissue of ALS patients and age-matched controls. The effect of NPY on ALS cortical pathophysiology was investigated using slice electrophysiology and multi-electrode array recordings of SOD1G93A cortical cultures in vitro. The impact of NPY on ALS disease trajectory was investigated by treating SOD1G93A mice intranasally with NPY and selective NPY receptor agonists and antagonists from pre-symptomatic and symptomatic phases of disease. RESULTS: In the human post-mortem ALS motor cortex, we observe a significant increase in NPY expression, which is not present in the somatosensory cortex. In vitro, we demonstrate that NPY can ameliorate ALS hyperexcitability, while brain-targeted nasal delivery of NPY and a selective NPY Y1 receptor antagonist modified survival and motor deficits specifically within the symptomatic phase of the disease in the ALS SOD1G93A mouse. INTERPRETATION: Taken together, these findings highlight the capacity for non-invasive brain-targeted interventions in ALS and support antagonism of NPY Y1Rs as a novel strategy to improve ALS motor function.

Fragile X Syndrome and Fetal Alcohol Syndrome: Occurrence of Dual Diagnosis in a Set of Triplets.

BACKGROUND: Fragile X syndrome (FXS) and fetal alcohol syndrome disorders are both common causes of intellectual disability in children. When both conditions are present in the same individual, the resultant phenotype may make identification of clinical issues and management challenging. CASE PRESENTATION: In this case report, we present a case of triplets who had significant in utero alcohol exposure; 2 of whom also have FXS and the other not having the fragile X mutation. The siblings with FXS have subtle differences in the physical phenotype compared with the other one, who has prominent features of partial fetal alcohol syndrome instead. However, all 3 siblings have intellectual impairment (although this is more severe in the 2 with FXS), meet diagnostic criteria for autism spectrum disorder, and present with severe behavioral challenges. The clinical presentation of the 2 siblings with FXS is much more severe as compared to a child with FXS alone, and this is likely due to the additive effect of in utero alcohol exposure and environmental factors. We discuss the combination of these 2 pathologies and how this can affect the overall clinical presentation. CONCLUSION: In the management of children with FXS, evaluation for other risk factors that can have neurobehavioral sequelae is important, and these can affect clinical presentation and prognosis.

The Benefits of Participating in a Learning Assistant Program on the Metacognitive Awareness and Motivation of Learning Assistants.

Learning assistant (LA) programs train undergraduate students to foster peer discussion and facilitate active-learning activities in undergraduate science, technology, engineering, and mathematics (STEM) classes. Students who take courses that are supported by LAs demonstrate better conceptual understanding, lower failure rates, and higher satisfaction with the course. There is less work, however, on the impact that participating in LA programs has on the LAs themselves. The current study implements a pretest-posttest design to assess changes in LAs' metacognition and motivation to succeed in STEM across their first and second quarters as an LA. Our findings suggest that participating in this program may help LAs become more reflective learners, as was demonstrated by an increase in their scores on the Metacognitive Awareness Inventory (MAI) after the first quarter. LAs also showed increases on the Intrinsic Motivation and Self-Efficacy subscales of the Science Motivation Questionnaire. Students who participated in the program for an additional quarter continued to show increases in their MAI scores and maintained the gains that were observed in their motivation. Taken together, this work suggests that, in addition to benefiting the learner, LA programs may have positive impacts on the LAs themselves.

Rating of physiotherapy student clinical performance in a paediatric setting: are assessors consistent in their rating of a simulated clinical student performance?

BACKGROUND: During workplace-based clinical placements, best practice assessment states students should expect consistency between assessors rating their performance. To assist clinical educators (CEs) to provide consistent assessment of physiotherapy student performance, nine paediatric vignettes depicting various standards of simulated student performance, as assessed by the Assessment of Physiotherapy Practice (APP), were developed. The APP defines adequate on the global rating scale (GRS) as the minimally acceptable standard for an entry-level physiotherapist. The project aimed to evaluate consistency of paediatric physiotherapy educators assessing simulated student performance using the APP GRS. METHODS: Three paediatric scenarios representing neurodevelopment across three age ranges, infant, toddler and adolescent, were developed and scripted that depicted a 'not adequate', 'adequate' and 'good-excellent' performance based on the APP GRS. An expert panel (n = 9) conducted face and content validation. Once agreement was reached for all scripts, each video was filmed. A purposive sample of physiotherapists providing paediatric clinical education in Australia were invited to participate in the study. Thirty-five CEs, with minimum 3-years clinical experience and had supervised a student within the past year, were sent three videos at four-week intervals. Videos depicted the same clinical scenario, however performance varied with each video. Participants rated the performance on the four categories: 'not adequate', 'adequate', 'good' and 'excellent' Consistency among raters was assessed using percentage agreement to establish reliability. RESULTS: The vignettes were assessed a combined total of 59 times. Across scenarios, percentage agreement at the not adequate level was 100%. In contrast, the adequate scenarios for the Infant, Toddler and Adolescent video failed to meet the 75% agreement level. However, when combining adequate or good-excellent, percentage agreement was > 86%. The study demonstrated strong consensus when comparing not adequate to adequate or better performance. Importantly, no performance scripted as not adequate was passed by any assessor. CONCLUSIONS: Experienced educators demonstrate consistency in identifying not adequate from adequate or good-excellent performance when assessing a simulated student performance using the APP. Recommendation for practice: These validated video vignettes will be a valuable training tool to improve educator consistency when assessing student performance in paediatric physiotherapy.

Targeted Treatments for Fragile X Syndrome.

The histories of targeted treatment trials in fragile X syndrome (FXS) are reviewed in animal studies and human trials. Advances in understanding the neurobiology of FXS have identified a number of pathways that are dysregulated in the absence of FMRP and are therefore pathways that can be targeted with new medication. The utilization of quantitative outcome measures to assess efficacy in multiple studies has improved the quality of more recent trials. Current treatment trials including the use of cannabidiol (CBD) topically and metformin orally have positive preliminary data, and both of these medications are available clinically. The use of the phosphodiesterase inhibitor (PDE4D), BPN1440, which raised the level of cAMP that is low in FXS has very promising results for improving cognition in adult males who underwent a controlled trial. There are many more targeted treatments that will undergo trials in FXS, so the future looks bright for new treatments.

Research-practice partnerships: Adapting a care coordination intervention for rural Veterans over 3 years at multiple sites.

PURPOSE: Rural Veterans are more likely than urban Veterans to qualify for community care (Veterans Health Administration [VHA]-paid care delivered outside of VHA) due to wait times ≥30 days and longer travel times for VHA care. For rural Veterans receiving both VHA and community care, suboptimal care coordination between VHA and community providers can result in poor follow-up and care fragmentation. We developed Telehealth-based Coordination of Non-VHA Care (TECNO Care) to address this problem. METHODS: We iteratively developed and adapted TECNO Care with partners from the VHA Office of Rural Health and site-based Home Telehealth Care in the Community programs. Using templated electronic health record notes, Home Telehealth nurses contacted Veterans monthly to facilitate communication with VHA/community providers, coordinate referrals, reconcile medications, and follow up on acute episodes. We evaluated TECNO Care using a patient-level, pre-post effectiveness assessment and rapid qualitative analysis with individual interviews of Veterans and VHA collaborators. Our primary effectiveness outcome was a validated care coordination quality measure. We calculated mean change scores for each care continuity domain. FINDINGS: Between March 2019 and October 2021, 83 Veterans received TECNO Care. Veterans were predominately White (86.4%) and male (88.6%) with mean age 71.4 years (SD 10.4). Quantitative data demonstrated improvements in perceived care coordination following TECNO Care in 7 categories. Qualitative interviews indicated that Veterans and Home Telehealth nurses perceived TECNO Care as beneficial and addressing an area of high need. CONCLUSIONS: TECNO Care appeared to improve the coordination of VHA and community care and was valued by Veterans.

Electrodeposition and analysis of thick bismuth films.

Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and semiconductors, to name a few. This work presents the electrodeposition of mechanically stable and homogenous bismuth films at micron-scale thicknesses. A simple one-step electrodeposition process using either a pulse/reverse or direct current source yielded thick, homogenous, and mechanically stable bismuth films. Morphology, electrochemical behavior, adhesion, and mechanical stability of bismuth coatings plated with varying parameters were characterized via optical profilometry, cyclic voltammetry, electron microscopy, and tribology. Scratch testing on thick electroplated coatings (> 100 µm) revealed similar wear resistance properties between the pulse/reverse plated and direct current electroplated films. This study presents a versatile bismuth electroplating process with the possibility to replace lead in radiation shields with an inexpensive, non-toxic metal, or to make industrially relevant electrocatalytic devices.

Implementing evidence-based telephone coaching for health behavior program enrollment: A quality improvement project.

INTRODUCTION: This program evaluation describes the use of implementation facilitation to support uptake of a telephone-based engagement coaching intervention, ACTIVATE, using paraprofessional staff, to support health behavior program enrollment. METHOD: The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework guided the formative evaluation. A mixed-methods approach was used to integrate qualitative (i.e., rapid analysis approach) and quantitative (i.e., descriptive statistics, chi-square test of independence, logistic regression) analyses for each outcome. RESULTS: Most patients (95%; 319 of 335) were offered ACTIVATE, and 82 patients completed ACTIVATE. Delivery with paraprofessional staff was feasible with adaptations for translation from research to a clinical setting, which are described. External facilitation (a form of implementation facilitation) was associated with higher reach. DISCUSSION: Delivery of telephone-based coaching by paraprofessional staff to support health behavior program enrollment was feasible. External facilitation was important to the translation of ACTIVATE from research to clinical practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An Innovation to Expand the Reach of Peer Support: A Feasibility and Acceptability Study.

INTRODUCTION: Peer support is a well-established part of veteran care and a cost-effective way to support individuals pursuing health behavior change. Common models of peer support, peer coaching, and mutual peer support have limitations that could be minimized by building on the strengths of each to increase the overall reach and effectiveness. We conducted a 12-week, proof-of-concept study to test the acceptability and feasibility of a hybrid model of peer support which supplements dyadic mutual peer support with as-needed peer coaching. MATERIALS AND METHODS: We tested our novel peer support model within the context of cardiovascular disease (CVD) risk reduction as a support mechanism for the promotion of heart-healthy diet and exercise behaviors. We recruited peer buddies (participants who would be matched with each other to provide mutual support) with at least one uncontrolled CVD risk factor (i.e., blood pressure, weight, or diabetes) and peer coaches (individuals who would provide additional, as-needed support for peer buddies) with a recent history of CVD health behavior improvement. We aimed for 50% of peer buddies to be women to assess for potential gender differences in intervention engagement. Participants received didactic instruction during three group sessions, and peer dyads were instructed to communicate weekly with their peer buddy to problem-solve around action plans and behavioral goals. We tracked frequency of dyadic communication and conducted semi-structured interviews at the intervention's end to assess acceptability. RESULTS: We recruited three peer coaches and 12 peer buddies. Ten buddies (five dyads) met at the first group session, and all were still in weekly contact with each other at week 12. Peer buddies had a mean of 8.75 out of 12 possible weekly peer buddy communications (range 6-15 in total). Peer coaches provided additional support to four participants over 12 weeks. Participants reported liking the intervention, including mixed-gender groups. Clarity and expectation setting around the role of peer coaches were important. CONCLUSIONS: The supplementation of mutual peer support with as-needed peer coaching is an acceptable and feasible way to expand the potential reach and effectiveness of peer support for behavior change among veterans.

Addressing Hypertension Outcomes Using Telehealth and Population Health Managers: Adaptations and Implementation Considerations.

PURPOSE OF REVIEW: There is a growing evidence base describing population health approaches to improve blood pressure control. We reviewed emerging trends in hypertension population health management and present implementation considerations from an intervention called Team-supported, Electronic health record-leveraged, Active Management (TEAM). By doing so, we highlight the role of population health managers, practitioners who use population level data and to proactively engage at-risk patients, in improving blood pressure control. RECENT FINDINGS: Within a population health paradigm, we discuss telehealth-delivered approaches to equitably improve hypertension care delivery. Additionally, we explore implementation considerations and complementary features of team-based, telehealth-delivered, population health management. By leveraging the unique role and expertise of a population health manager as core member of team-based telehealth, health systems can implement a cost-effective and scalable intervention that addresses multi-level barriers to hypertension care delivery. We describe the literature of telehealth-based population health management for patients with hypertension. Using the TEAM intervention as a case study, we then present implementation considerations and intervention adaptations to integrate a population health manager within the health care team and effectively manage hypertension for a defined patient population. We emphasize practical considerations to inform implementation, scaling, and sustainability. We highlight future research directions to advance the field and support translational efforts in diverse clinical and community contexts.

Prosaccade and Antisaccade Behavior in Fragile X-Associated Tremor/Ataxia Syndrome Progression.

Background: Quantitative measurement of eye movements can reveal subtle progression in neurodegenerative diseases. Objective: To determine if quantitative measurements of eye movements may reveal subtle progression of fragile X-associated tremor and ataxia (FXTAS). Methods: Prosaccade (PS) and antisaccade (AS) behavior was analyzed in 25 controls, 57 non-FXTAS carriers, and 46 carriers with FXTAS. Results: Symptomatic individuals with FXTAS had longer AS latencies, increased rates of AS errors, and increased AS dysmetria relative to non-FXTAS carriers and controls. These deficits, along with PS latency and velocity, were greater in advanced FXTAS stages. Conclusion: AS deficits differentiated FXTAS from non-FXTAS premutation carriers implicating top-down control and frontostriatal deterioration. However, the absence of group differences between non-FXTAS carriers and controls in AS and PS markers suggests saccade performance may not be a sensitive enough measure for detecting conversion to FXTAS, but instead more helpful as translational biomarkers of FXTAS progression.

Estrogen Enhances Dendrite Spine Function and Recovers Deficits in Neuroplasticity in the prpTDP-43A315T Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) attacks the corticomotor system, with motor cortex function affected early in disease. Younger females have a lower relative risk of succumbing to ALS than males and older females, implicating a role for female sex hormones in disease progression. However, the mechanisms driving this dimorphic incidence are still largely unknown. We endeavoured to determine if estrogen mitigates disease progression and pathogenesis, focussing upon the dendritic spine as a site of action. Using two-photon live imaging we identify, in the prpTDP-43A315T mouse model of ALS, that dendritic spines in the male motor cortex have a reduced capacity for remodelling than their wild-type controls. In contrast, females show higher capacity for remodelling, with peak plasticity corresponding to highest estrogen levels during the estrous cycle. Estrogen manipulation through ovariectomies and estrogen replacement with 17ß estradiol in vivo was found to significantly alter spine density and mitigate disease severity. Collectively, these findings reveal that synpatic plasticity is reduced in ALS, which can be amelioriated with estrogen, in conjuction with improved disease outcomes.

Targeted regulation of autophagy using nanoparticles: New insight into cancer therapy.

Normal cells depend on autophagy to maintain cellular homeostasis by recycling damaged organelles and misfolded proteins and degrading toxic agents. Similar to apoptosis, targeting autophagy has been under attention in cancer therapy. However, autophagy has both pro-survival and pro-death functions in tumors, and its targeting requires further elucidation. The current review focuses on using nanoparticles for targeting autophagy in cancer treatment. Nanocarriers can deliver autophagy regulators along with chemotherapeutic agents leading to intracellular accumulation in cancer cells and synergistic cancer therapy. Furthermore, genetic tools such as siRNA and shRNA can be used for targeting molecular components that regulate autophagy, such as the ATG12-ATG5-ATG16L1 complex. A number of nanostructures, such as gold and zinc oxide nanoparticles, can be used to enhance oxidative stress-mediated apoptosis and autophagy, reducing cancer progression. Further, using nanoparticles to modulate autophagy potentiates the anti-tumor effects of cisplatin and gefitinib during chemotherapy. Polymeric nanoparticles, lipid-based nanostructures and carbon-based nanomaterials are among other nanoparticles capable of regulating autophagy in cancer cells. Of note, various regulatory components of autophagy such as ATGs, Beclin-1 and LC3-II can be affected by nanomaterials. Based on the role of nanomaterial-induced autophagy as pro-survival or pro-death, further targeting can potentiate the fight against cancer cells.

Association between angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin-II receptor 1 (AGTR1) polymorphisms and COVID-19 infection in the southeast of Iran: a preliminary case-control study.

BACKGROUND: The COVID-19 pandemic remains an emerging public health crisis with serious adverse effects. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV--2) infection, targeting angiotensin-converting enzyme-2 (ACE2) receptor for cell entry. However, changes in the renin-angiotensin system (RAS) balance alter an individual's susceptibility to COVID-19 infection. We aimed to evaluate the association between AGT rs699 C > T, ACE rs4646994 I/D, and AGTR1 rs5186 C > A variants and the risk of COVID-19 infection and the severity in a sample of the southeast Iranian population. METHODS: A total of 504 subjects, including 258 COVID-19 positives, and 246 healthy controls, were recruited. Genotyping of the ACE gene rs4646994, and AGT rs699, and AGTR1 rs5186 polymorphisms was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. RESULTS: Our results showed that the II genotype of ACE rs4646994 and the I allele decreased the risk of COVID-19 infection. Moreover, we found that the TC genotype and C allele of AGT rs699 increased the risk of COVID-19 infection. The AGTR1 rs5186 was not associated with COVID-19 infection. Also, we did not find any association between these polymorphisms and the severity of the disease. However, we found a significantly higher age and prevalence of diabetes and hypertension in patients with severe disease than a non-severe disease. CONCLUSIONS: These findings suggest that ACE rs4646994 and AGT rs699 polymorphisms increase the risk of COVID-19 infection in a southeast Iranian population.

Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome.

This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (FMR1) gene, in addition to an apolipoprotein E (APOE) ε4 allele. FXTAS and Alzheimer's Disease (AD) are late-onset neurodegenerative diseases that share overlapping cognitive deficits including processing speed, working memory and executive function. The prevalence of coexistent FXTAS-AD pathology remains unknown. The clinical picture in this case was marked with rapid cognitive decline between age 67 and 71 years in addition to remarkable MRI changes. Over the 16 months between the two clinical evaluations, the brain atrophied 4.12% while the lateral ventricles increased 26.4% and white matter hyperintensities (WMH) volume increased 15.6%. Other regions atrophied substantially faster than the whole brain included the thalamus (-6.28%), globus pallidus (-10.95%), hippocampus (-6.95%), and amygdala (-7.58%). A detailed postmortem assessment included an MRI with confluent WMH and evidence of cerebral microbleeds (CMB). The histopathological study demonstrated FXTAS inclusions in neurons and astrocytes, a widespread presence of phosphorylated tau protein and, amyloid ß plaques in cortical areas and the hippocampus. CMBs were noticed in the precentral gyrus, middle temporal gyrus, visual cortex, and brainstem. There were high amounts of iron deposits in the globus pallidus and the putamen consistent with MRI findings. We hypothesize that coexistent FXTAS-AD neuropathology contributed to the steep decline in cognitive abilities.

Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS.

Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.

Applied Rapid Qualitative Analysis to Develop a Contextually Appropriate Intervention and Increase the Likelihood of Uptake.

BACKGROUND: Rapid approaches to collecting and analyzing qualitative interview data can accelerate discovery timelines and intervention development while maintaining scientific rigor. We describe the application of these methods to a program designed to improve care coordination between the Veterans Health Administration (VHA) and community providers. METHODS: Care coordination between VHA and community providers can be challenging in rural areas. The Telehealth-based Coordination of Non-VHA Care (TECNO Care) intervention was designed to improve care coordination among VHA and community providers. To ensure contextually appropriate implementation of TECNO Care, we conducted preimplementation interviews with veterans, VHA administrators, and VHA and community providers involved in community care. Using both a rapid approach and qualitative analysis, an interviewer and 1-2 note-taker(s) conducted interviews. RESULTS: Over 5 months, 18 stakeholders were interviewed and we analyzed these data to identify how best to deliver TECNO Care. Responses relevant to improving care coordination include health system characteristics; target population; metrics and outcomes; challenges with the current system; and core components. Veterans who frequently visit VHA or community providers and are referred for additional services are at risk for poor outcomes and may benefit from additional care coordination. Using these data, we designed TECNO Care to include information on VHA services and processes, assist in the timely completion of referrals, and facilitate record sharing. CONCLUSION: Rapid qualitative analysis can inform near real-time intervention development and ensure relevant content creation while setting the stage for stakeholder buy-in. Rigorous and timely analyses support the delivery of contextually appropriate, efficient, high-value patient care.

Improving cardiovascular outcomes by using team-supported, EHR-leveraged, active management: Disseminating a successful quality improvement project.

BACKGROUND: Uncontrolled blood pressure (BP) is common among Veterans. Rural Veterans are at risk for suboptimal care coordination as successful programs may be implemented at lower rates due to individual- and system-level factors. There is strong evidence to support the use of remotely delivered support and patient-generated data from home BP monitors and virtual BP visits to manage BP. OBJECTIVE: The purpose of this project is to augment the current approach to addressing uncontrolled BP so that existing clinical staff can reach a larger patient population. METHODS: Our project will address uncontrolled BP by leveraging team-based care, the Veteran's Health Administration Electronic Health Record, and patient-centered medical home data to address patient, provider, and system barriers to cardiovascular disease (CVD) preventive care. We will implement this project in cardiovascular disease practices in three rural Veterans Health Administration clinics. We will evaluate implementation processes as well as patient-level (e.g., clinical outcomes, referrals to specialty services) outcomes in a one-arm, pre-post design. DISCUSSION: This manuscript describes our process in expanding the implementation of a successful project to improve BP control in high-risk, rural Veterans. Findings from our study will inform an understanding of both implementation and clinical effectiveness outcomes of a potentially scalable BP intervention in rural, community-based clinics. Appropriate management of Veterans with uncontrolled BP can reduce morbidity and mortality related to CVD. In turn, improvements in BP, can lead to improved quality metrics and potentially decrease costs for a healthcare system.