Design of an Ara h 2 hypoallergen from conformational epitopes.

INTRODUCTION: Adverse reactions are relatively common during peanut oral immunotherapy. To reduce the risk to the patient, some researchers have proposed modifying the allergen to reduce IgE reactivity, creating a putative hypoallergen. Analysis of recently cloned human IgG from patients treated with peanut immunotherapy suggested that there are three common conformational epitopes for the major peanut allergen Ara h 2. We sought to test if structural information on these epitopes could indicate mutagenesis targets for designing a hypoallergen and evaluated the reduction in IgE binding via immunochemistry and a mouse model of passive cutaneous anaphylaxis (PCA). METHODS: X-ray crystallography characterized the conformational epitopes in detail, followed by mutational analysis of key residues to modify monoclonal antibody (mAb) and serum IgE binding, assessed by ELISA and biolayer interferometry. A designed Ara h 2 hypoallergen was tested for reduced vascularization in mouse PCA experiments using pooled peanut allergic patient serum. RESULTS: A ternary crystal structure of Ara h 2 in complex with patient antibodies 13T1 and 13T5 was determined. Site-specific mutants were designed that reduced 13T1, 13T5, and 22S1 mAbs binding by orders of magnitude. By combining designed mutations from the three major conformational bins, a hexamutant (Ara h 2 E46R, E89R, E97R, E114R, Q146A, R147E) was created that reduced IgE binding in serum from allergic patients. Further, in the PCA model where mice were primed with peanut allergic patient serum, reactivity upon allergen challenge was significantly decreased using the hexamutant. CONCLUSION: These studies demonstrate that prior knowledge of common conformational epitopes can be used to engineer reduced IgE reactivity, an important first step in hypoallergen design.

Occupational Health Providers' Perceptions of Employee Vaccine Hesitancy.

OBJECTIVE: This study examined the perspectives of occupational health providers (OHPs) on the most frequently encountered clinically relevant reasons for employee vaccine hesitancy. METHODS: We conducted an anonymous, online, cross-sectional survey of US OHPs ( N = 217). The survey asked OHPs about the major reasons that employees cite for being unwilling to receive the following three categories of vaccines: COVID-19, annual influenza, and others relevant to the workplace. RESULTS: Concern about adverse effects was the most frequently reported reason for employee vaccine hesitancy for each vaccine category. Mistrust was reported more frequently for COVID-19 than for the influenza vaccine or other vaccines (χ 2P < 0.05). Targets of employee mistrust included government and researchers or scientists, but mistrust of healthcare providers was uncommon. CONCLUSIONS: These results can be used to inform interventions to address vaccine hesitancy in the occupational health setting.

Perspectives on Benefits and Challenges to Developing a Co-Teaching and Co-Learning Exchange between Community and Academic Partners.

BACKGROUND: To train future professionals in health disparities and social determinants of health, academic health centers often use curricula exclusively developed and instructed by faculty. OBJECTIVE: To examine the perceptions and attitudes of faculty and community stakeholders towards the benefits of and challenges to developing co-teaching/co-learning exchange programs. METHODS: Faculty from six academic professional schools at a single institution and community members participated in focus groups. Interviews were video-recorded and reviewed for themes. RESULTS: Both faculty and community participants felt that partnering in the design and implementation of lectures addressing the social determinants of health could enhance curriculum and provide real-world context for the learning experience. CONCLUSIONS: Our findings add to the literature examining the benefits and challenges of engagement between faculty and community and offer new insights on the value of co-teaching/co-learning experiences.

The Emerging Leaders in Public Health Initiative: Individual Leadership Transformation.

The Emerging Leaders in Public Health (ELPH) Initiative, sponsored by The Kresge Foundation, provided leadership development to local governmental public health leaders. An adaptive leadership framework was used to shape the curriculum. The coleads attended multiday convenings and webinars over a 16- to 18-month period. Key components of the initiative included using applied learning to solidify their leadership skills as they worked to develop a new role for their agencies provision of a resource grant from The Kresge Foundation to support agency transformation and technical assistance and consultation provided by a National Program Office. An external evaluator conducted a multicomponent evaluation of individual leadership skill change. Graduates assessed change in their own leadership and change in their colead. Colleagues of ELPH participants were surveyed about their observed changes in the leadership actions of the program graduates. One hundred four leaders from 30 states participated in the initiative in 3 successive cohorts. Leaders demonstrated improvement as shown by self-report and external observation. Improved ability to communicate in a way that inspires others was one of the most significant changes in leadership behaviors. Additional leadership actions were strengthened including the ability to create and maintain high-performing teams, the ability to ask transformational questions, and the ability to actively listen to understand. The pandemic has shown the importance of developing the field, starting with leadership. Leadership development and agency transformation are synergistic; they depend on each other and support each other.

The Emerging Leaders in Public Health Initiative: Leadership Development to Advance Public Health Practice.

CONTEXT: Effective leadership is essential for governmental public health agencies to promote and protect the health of their communities. OBJECTIVE: The Emerging Leaders in Public Health Initiative, a program of The Kresge Foundation, was implemented to strengthen leadership in governmental public health. We seek to examine lessons from the initiative to contribute to the field a better understanding of leadership development practices. DESIGN: An external evaluator conducted a retrospective analysis of participant responses postinitiative to assess the overall impact of the initiative and explore which components were most valuable. SETTING: United States. PARTICIPANTS: Directors and other staff from governmental public health agencies were recruited in 2-person teams to participate in 3 successive cohorts. INTERVENTION: Drawn from adaptive leadership principles, a framework was developed to guide the selection and implementation of educational and experiential activities. Participants were challenged to develop a new role for their public health agency, which provided a learning laboratory to practice individual and team leadership skills. The Kresge Foundation provided participants with a resource grant and a National Program Office offered convenings, webinars, coaching, and technical assistance over the 18 months of the developmental experience. MAIN OUTCOME MEASURES: Satisfaction, perceived value of components, and future intentions were assessed from participants in cohorts II and III (n = 70). The overall response rate was 93%. RESULTS: One hundred four diverse leaders from 52 agencies, representing 30 states participated in the initiative. Participants were extremely satisfied with the program (94%) and indicated a strong likelihood of recommending it to a colleague (96%). Unrestricted grant funding, peer learning, and in-person learning sessions were the program components rated most highly valuable. CONCLUSIONS: This initiative offers insights into principles and processes to be considered for future public health leadership development.

Adapting the Evidence Academy model for virtual stakeholder engagement in a national setting during the COVID-19 pandemic.

The COVID-19 pandemic raised the importance of adaptive capacity and preparedness when engaging historically marginalized populations in research and practice. The Rapid Acceleration of Diagnostics in Underserved Populations' COVID-19 Equity Evidence Academy Series (RADx-UP EA) is a virtual, national, interactive conference model designed to support and engage community-academic partnerships in a collaborative effort to improve practices that overcome disparities in SARS-CoV-2 testing and testing technologies. The RADx-UP EA promotes information sharing, critical reflection and discussion, and creation of translatable strategies for health equity. Staff and faculty from the RADx-UP Coordination and Data Collection Center developed three EA events with diverse geographic, racial, and ethnic representation of attendees from RADx-UP community-academic project teams: February 2021 (n = 319); November 2021 (n = 242); and September 2022 (n = 254). Each EA event included a data profile; 2-day, virtual event; event summary report; community dissemination product; and an evaluation strategy. Operational and translational delivery processes were iteratively adapted for each EA across one or more of five adaptive capacity domains: assets, knowledge and learning, social organization, flexibility, and innovation. The RADx-UP EA model can be generalized beyond RADx-UP and tailored by community and academic input to respond to local or national health emergencies.

The CTSA Diversity, Equity, Inclusion, and Accessibility (DEIA) Task Force's recommendations for the CTSA program consortium.

The Clinical and Translational Science Award (CTSA) Program recognizes that advancing diversity, equity, inclusion, and accessibility (DEIA) requires moving beyond statements of commitment to transformative actions. In 2021, the CTSA Program created a Task Force (TF) to initiate work in support of structural and transformational initiatives that advance DEIA for the consortium and its individual hubs. We describe the process of forming the expertise-driven (DEIA) TF and our activities to date. We 1) developed and adopted the DEIA Learning Systems Framework to guide our approach; 2) defined a set of recommendations across four focus areas (Institutional; Programmatic; Community-Centered; and Social, Cultural, Environmental); and 3) designed and disseminated a survey to capture the CTSA Program's baseline demographic, community, infrastructural, and leadership diversity. The CTSA Consortium also elevated the TF to a standing Committee to extend our understanding, development, and implementation of DEIA approaches to translational and clinical science. These initial steps provide a foundation for collectively fostering environment that support DEIA across the research continuum.

Building diverse leadership in an academic medical center: The ACCLAIM program.

As healthcare systems become more complex, medical education needs to adapt in many ways. There is a growing need for more formal leadership learning for healthcare providers, including greater attention to health disparities. An important challenge in addressing health disparities is ensuring inclusive excellence in the leadership of healthcare systems and medical education. Women and those who are underrepresented in medicine (URMs) have historically had fewer opportunities for leadership development and are less likely to hold leadership roles and receive promotions. One successful initiative for improved learning of medical leadership-presented as a case example here-is the Academic Career Leadership Academy in Medicine (ACCLAIM) at the University of North Carolina at Chapel Hill School of Medicine. ACCLAIM is uniquely designed for faculty identified as having emerging leadership potential, with an emphasis on women and URMs. Using a leadership learning system approach, annual cohorts of participants (Scholars) interactively participate in a multi-faceted nine-month long learning experience, including group (e.g., guest-speaker weekly presentations and exercises) and individual learning components (e.g., an individual leadership project). Since its initiation in 2012 and through 2021, 111 Scholars have participated in ACCLAIM; included were 57% women and 27% URMs. Two important outcomes described are: short-term impact as illustrated by consistent improvements in quantitively measured leadership knowledge and capabilities; and long-term leadership growth, whereby half of the ACCLAIM graduates have received academic rank promotions and almost two-thirds have achieved new leadership opportunities, with even higher percentages observed for women and URMs; for example, 87% of URMs were either promoted or achieved new leadership positions. Also consistently noted, through qualitative assessments, are broader healthcare system knowledge and shared tactics for addressing common challenges among Scholars. This case example shows that the promotion of leadership equity may jointly enhance professional development while creating opportunities for systems change within academic medical centers. Such an approach can be a potential model for academic medical institutions and other healthcare schools seeking to promote leadership equity and inclusion.

Bridging the Urban-Rural Divide in Chronic Disease Through Community Engagement in Health Program Delivery.

The urban-rural divide in chronic disease contributes to persistent geographic disparities in life expectancy in North Carolina. Policies and programs in resource-constrained rural areas should be designed to increase health equity and reduce this continuing divide by including greater community engagement and decision-making for meaningful, sustainable change.

An assessment of the Libyan baccalaureate nursing education during political turmoil.

Since the Libyan Revolution in 2011, the country's nursing workforce has been struggling. Libyan nursing schools have focused on rebuilding the country's supply of nurses after many emigrated. Wanting to infuse the workforce with more baccalaureate-prepared nurses, Libyan nursing faculty invited nursing and public health representatives from a US-based academic medical institution and a non-governmental medical organization to collaborate with local stakeholders in a country-wide assessment. The purpose of this article is to outline the national programs' strengths and weaknesses and make recommendations for developing a strategy to elevate nursing education to meet international standards. This can serve as a launching point to strengthen Libya's health services provision capacity, particularly during this time of transition when opportunities may become available to move in new directions. The approach and findings may have wider application to other countries who are similarly experiencing civil and political turmoil.

The role of stress responses on engagement in dietary and physical activity behaviors among Latino adults living with prediabetes.

OBJECTIVES: Latinos are at a high risk of developing type 2 diabetes (T2D). Prediabetes is a major risk factor for T2D; however, progression to T2D can be slowed with engagement in healthy behaviors. Stress can hinder engagement with health behaviors. Qualitative methods were used to understand how Latinos with prediabetes attempted to modify their diet and physical activity behaviors to slow T2D progression and how stress affected their engagement in these behaviors. DESIGN: Semi-structured interviews were conducted with 20 Latinos with prediabetes in North Carolina. Participants were asked questions about types of stress they experienced and how stress affected their health. We generated codes on stress and stress responses and used content analysis to organize codes between and within participants. RESULTS: Behaviors changed after prediabetes diagnosis. Few participants reported changing their physical activity, however, all participants attempted to change their eating patterns by changing food types consumed and reducing portion sizes. The stress participants experienced impacted their ability to self-regulate their diet. They reported overeating or appetite suppression during stressful periods. Stress also affected cognitive responses by compromising healthy decision-making and instigating negative emotional reactions. Overall, stress complicated participants' ability to properly engage in recommended behaviors by negatively impacting participants' behavioral self-regulation and cognitive processes. CONCLUSIONS: Stress affects behavioral and cognitive progresses that adversely alters primarily dietary behaviors. Tailored plans acknowledging the impact of stress and providing coping and supportive help for dealing with stress may enhance engagement in healthy behaviors for Latinos with prediabetes.

Recognizing Cross-Institutional Fiscal and Administrative Barriers and Facilitators to Conducting Community-Engaged Clinical and Translational Research.

PURPOSE: This qualitative study examined fiscal and administrative (i.e., pre- and post-award grants process) barriers and facilitators to community-engaged research among stakeholders across 4 Clinical and Translational Science Awards (CTSA) institutions. METHOD: A purposive sample of 24 key informants from 3 stakeholder groups-community partners, academic researchers, and research administrators-from the CTSA institutions at the University of North Carolina at Chapel Hill, Medical University of South Carolina, Vanderbilt University Medical Center, and Yale University participated. Semistructured interviews were conducted in March-July 2018, including questions about perceived challenges and best practices in fiscal and administrative processes in community-engaged research. Transcribed interviews were independently reviewed and analyzed using the Rapid Assessment Process to facilitate key theme and quote identification. RESULTS: Community partners were predominantly Black, academic researchers and research administrators were predominantly White, and women made up two-thirds of the overall sample. Five key themes were identified: level of partnership equity, partnership collaboration and communication, institutional policies and procedures, level of familiarity with varying fiscal and administrative processes, and financial management expectations. No stakeholders reported best practices for the institutional policies and procedures theme. Cross-cutting challenges included communication gaps between stakeholder groups; lack of or limits in supporting community partners' fiscal capacity; and lack of collective awareness of each stakeholder group's processes, procedures, and needs. Cross-cutting best practices centered on shared decision making and early and timely communication between all stakeholder groups in both pre- and post-award processes. CONCLUSIONS: Findings highlight the importance of equitable processes, triangulated communication, transparency, and recognizing and respecting different financial management cultures within community-engaged research. This work can be a springboard used by CTSA institutions to build on available resources that facilitate co-learning and discussions between community partners, academic researchers, and research administrators on fiscal readiness and administrative processes for improved community-engaged research partnerships.

Action Learning Cohort Series: An Innovative Community-Engaged Approach for Translating Research Into Practice.

Cultivating strong partnerships among community and academic stakeholders expedites the translation of research findings into practice and communities by enhancing opportunities for research dissemination and implementation. However, the lack of systematic methods for community stakeholder engagement may decelerate the translational research process. The North Carolina Translational Research and Clinical Sciences Institute implemented an innovative approach to community engagement called the Action Learning Cohort (ALC) Series. The ALC Series, a workgroup extension of a professional conference, used action learning and systems thinking strategies to conceptualize and develop a product aimed at preventing, treating, and controlling hypertension in eastern North Carolina. We evaluated the acceptability and practicality of the ALC Series using survey, focus group, and interview pilot data. Action learning and systems thinking strategies led ALC stakeholders to develop and disseminate The Empathy Building Resource Guide: A Toolkit for Enhancing Patient-Provider Relationships in the Treatment, Management, and Prevention of Hypertension. Stakeholders rated the Series as satisfactory and acknowledged gains in knowledge and desire for engagement with fellow ALC stakeholders beyond the Series. The ALC Series approach is a potentially practical and acceptable model for systematically engaging community stakeholders in translating knowledge into a product that addresses health topics like hypertension.

Integrating Registered Dietitian Nutritionists Into Primary Care Practices to Work With Children With Overweight.

Despite increased reimbursement for registered dietitian nutritionists (RDNs), few studies have assessed the potential of integrating them into primary care clinics to support pediatric weight management. To assess the feasibility and effectiveness of this approach, RDNs were introduced into 8 primary care practices in North Carolina. This mixed-methods study combined (1) interviews and focus groups with RDNs and clinic personnel, (2) comparison of change in body mass index (BMI) z-score in study practices to change in historical comparison groups, and (3) analysis of behavior and BMI change for RDN utilizers. Qualitative data were coded thematically, and McNemar's and Wilcoxon signed-rank tests were used for quantitative data. RDN integration was good, but average referral rate for eligible children was 19.4%; 48.4% of those referred utilized the RDN (most fewer than 3 times). Using the full analysis set, there was no difference in change in BMI z-score for intervention and comparison groups. For RDN utilizers, the average change in BMI z-score was -0.089 (P < .001), and there was statistically significant improvement in 7 of 8 health behaviors. Integrating RDNs into primary care practices was feasible and possibly effective for utilizers. Reaping potential benefits of RDN co-location would require increasing low referral and utilization rates.

Aligning community-engaged research competencies with online training resources across the Clinical and Translational Science Award Consortium.

INTRODUCTION: The extent to which Clinical and Translational Science Award (CTSA) programs offer publicly accessible online resources for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged publicly accessible online CEnR resources from CTSAs and mapped resources to CEnR core competency domains. METHODS: Following a search and review of the current literature regarding CEnR competencies, CEnR core competency domains were identified and defined. A systematic review of publicly accessible online CEnR resources from all 64 current CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for the inclusion of each CEnR core competency domain. Domain scores across all resources were assessed using descriptive statistics. RESULTS: Eight CEnR core competency domains were identified. Overall, 214 CEnR resources publicly accessible online from 35 CTSAs were eligible for review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. "CEnR methods" (50.5%) and "Knowledge and relationships with communities" (40.2%) were the most frequently addressed domains, while "CEnR program evaluation" (12.1%) and "Dissemination and advocacy" (11.2%) were the least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. CONCLUSIONS: Our findings guide CEnR stakeholders to identify publicly accessible online resources and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competency is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability.

Identification of the amino-terminal fragment of Ara h 1 as a major target of the IgE-binding activity in the basic peanut protein fraction.

BACKGROUND: Small, basic peanut proteins are often poorly extracted in pH-neutral buffers that are optimal for the extraction of peanut storage proteins such as Ara h 1. As a result, such proteins are easily missed as potential allergens. OBJECTIVE: To analyse the allergenic composition of the basic peanut protein (BPP) fraction. METHODS: A peanut extract prepared at pH 4 was fractionated by physicochemical procedures. Chemical analysis was performed by SDS-PAGE and mass spectrometry. Because immunoblotting was found to be inefficient for most of these small basic proteins, IgE-binding activity was measured by coupling the fractions to CNBr-activated Sepharose, followed by incubation with sera from 55 Dutch peanut-allergic children and 125 I-labelled anti-IgE. RESULTS: Most IgE reactivity of the BPP fraction was due to the 5-7 kDa amino-terminal fragment of Ara h 1. This finding was confirmed by the use of the fragment in recombinant form, to which 25/55 of the sera was IgE-positive. CONCLUSION: The amino-terminal fragment of Ara h 1, a member of a family of small anti-microbial proteins, is an allergen independent of the carboxy-terminal fragment of Ara h 1.

Long-term Safety of Minimally Invasive Left Ventricular Assist Device Discontinuation for Myocardial Recovery.

BACKGROUND: Left ventricular assist devices (LVADs) play important roles in advanced heart failure (HF) management. In patients who experience myocardial recovery, the LVAD is often explanted via a resternotomy, which may negatively impact the newly recovered heart. We describe a case-series of LVAD discontinuation using a minimally invasive approach, focusing on thromboembolic phenomenon and infection rates in long-term follow-up. METHODS: Our study is a single-center, retrospective case series of patients with myocardial recovery after mechanical unloading with an LVAD. Patients underwent outflow graft ligation through a minimally invasive approach with driveline excision. Postdiscontinuation, patients obtained serial transthoracic echocardiograms for a minimum of 6 months and followed with our heart failure specialist. RESULTS: All 7 recovery patients had nonischemic cardiomyopathy and included 4 women (57%). Mean age was 44.3 ± 15.6 years. Median LVAD support duration was 454 (interquartile range, 326 to 1096) days. Intensive care unit length of stay and total length of stay were 3.4 ± 1.9 days and 6.3 ± 2.3 days, respectively. Blood transfusion rate was 0.86 ± 1.1 units. At a median follow-up of 874 (interquartile range, 864 to 1007) days, no patients developed thromboembolic phenomena despite use of aspirin only for prophylaxis. One patient experienced driveline infection, who had persistent driveline infection before procedure. CONCLUSIONS: This minimally invasive approach for LVAD discontinuation through outflow graft ligation, driveline removal, and LVAD stoppage in setting of myocardial recovery avoids resternotomy risks. Despite leaving the LVAD in situ, there was no risk of thromboembolism or infection associated with residual hardware.