Native Pathways to Health: A Culturally Grounded and Asset-based CBPR Project Exploring the Health of North Carolina's American Indian Communities.

Among the eight tribes within North Carolina, American Indian communities experience disparate rates of poverty, low education, chronic disease, low access to health care, and low quality of life. Addressing inequities and knowledge gaps will require novel and culturally appropriate approaches designed in partnership with AI communities, and should be underscored by the cultural assets those communities possess.

Lessons Learned From a Community-Based Participatory Research Mental Health Promotion Program for American Indian Youth.

Background American Indian (AI) youth have the highest rates of suicide among racial/ethnic minority groups in the United States. Community-based strategies are essential to address this issue, and community-based participatory research (CBPR) offers a model to engage AI communities in mental health promotion programming. Objectives This article describes successes and challenges of a CBPR, mixed-method project, The Lumbee Rite of Passage (LROP), an academic-community partnership to develop and implement a suicide prevention program for Lumbee AI youth in North Carolina. Method LROP was conducted in two phases to (1) understand knowledge and perceptions of existing mental health resources and (2) develop, implement, and evaluate a cultural enrichment program as a means of suicide prevention. Discussion/Results LROP implemented an effective community-academic partnership by (1) identifying and understanding community contexts, (2) maintaining equitable partnerships, and (3) implementing a culturally tailored research design targeting multilevel changes to support mental health. Strategies formed from the partnership alleviated challenges in each of these key CBPR concept areas. Conclusions LROP highlights how a CBPR approach contributes to positive outcomes and identifies opportunities for future collaboration in a tribal community. Using culturally appropriate CBPR strategies is critical to achieving sustainable, effective programs to improve mental health of AI youth.

Community Health Asset Mapping Partnership Engages Hispanic/Latino Health Seekers and Providers.

BACKGROUND: The Hispanic/Latino population in Forsyth County, North Carolina, is growing quickly and experiencing significant disparities in access to care and health outcomes. Assessing community perceptions and utilization of health care resources in order to improve health equity among Hispanics/Latinos at both the county and state levels is critical. METHODS: Our community engagement process was guided by the Community Health Assets Mapping Partnerships (CHAMP) approach, which helps identify gaps in health care availability and areas for immediate action to improve access to and quality of health care. Specifically, we invited and encouraged the Hispanic/Latino population to participate in 4 different workshops conducted in Spanish or English. Participants were identified as either health care providers, defined as anyone who provides health care or a related service, or health care seekers, defined as anyone who utilizes such services. RESULTS: The most commonly cited challenges to access to care were cost of health care, documentation status, lack of public transportation, racism, lack of care, lack of respect, and education/language. These data were utilized to drive continued engagement with the Hispanic community, and action steps were outlined. LIMITATIONS: While participation in the workshops was acceptable, greater representation of health care seekers and community providers is needed. CONCLUSIONS: This process is fundamental to multilevel initiatives under way to develop trust and improve relationships between the Hispanic/Latino community and local health care entities in Forsyth County. Follow-through on recommended action steps will continue to further identify disparities, close gaps in care, and potentially impact local and state policies with regard to improving the health status of the Hispanic/Latino community.

Rationale and Design of the Echocardiographic Study of Hispanics/Latinos (ECHO-SOL).

BACKGROUND: Information regarding the prevalence and determinants of cardiac structure and function (systolic and diastolic) among the various Hispanic background groups in the United States is limited. METHODS AND RESULTS: The Echocardiographic Study of Latinos (ECHO-SOL) ancillary study recruited 1,824 participants through a stratified-sampling process representative of the population-based Hispanic Communities Health Study - Study of Latinos (HCHS-SOL) across four sites (Bronx, NY; Chicago, Ill; San Diego, Calif; Miami, Fla). The HCHS-SOL baseline cohort did not include an echo exam. ECHO-SOL added the echocardiographic assessment of cardiac structure and function to an array of existing HCHS-SOL baseline clinical, psychosocial, and socioeconomic data and provides sufficient statistical power for comparisons among the Hispanic subgroups. Standard two-dimensional (2D) echocardiography protocol, including M-mode, spectral, color and tissue Doppler study was performed. The main objectives were to: 1) characterize cardiac structure and function and its determinants among Hispanics and Hispanic subgroups; and 2) determine the contributions of specific psychosocial factors (acculturation and familismo) to cardiac structure and function among Hispanics. CONCLUSION: We describe the design, methods and rationale of currently the largest and most comprehensive study of cardiac structure and function exclusively among US Hispanics. ECHO-SOL aims to enhance our understanding of Hispanic cardiovascular health as well as help untangle the relative importance of Hispanic subgroup heterogeneity and sociocultural factors on cardiac structure and function.

Scaffold-focused virtual screening: prospective application to the discovery of TTK inhibitors.

We describe and apply a scaffold-focused virtual screen based upon scaffold trees to the mitotic kinase TTK (MPS1). Using level 1 of the scaffold tree, we perform both 2D and 3D similarity searches between a query scaffold and a level 1 scaffold library derived from a 2 million compound library; 98 compounds from 27 unique top-ranked level 1 scaffolds are selected for biochemical screening. We show that this scaffold-focused virtual screen prospectively identifies eight confirmed active compounds that are structurally differentiated from the query compound. In comparison, 100 compounds were selected for biochemical screening using a virtual screen based upon whole molecule similarity resulting in 12 confirmed active compounds that are structurally similar to the query compound. We elucidated the binding mode for four of the eight confirmed scaffold hops to TTK by determining their protein-ligand crystal structures; each represents a ligand-efficient scaffold for inhibitor design.

Qualitative Perceptions of an Anticipated Fresh Food Prescription Program.

Objective: Food insecurity (FI) is a growing public health problem. Produce prescriptions are known to improve healthy eating and decrease FI; however, few studies have incorporated community voice prior to its implementation. In this study, we aimed to elicit perspectives of individuals at risk for FI and the potential impact of a fresh food prescription (FFRx) program. Methods: We conducted this qualitative descriptive study through an academic medical center in collaboration with community partners. We conducted focus groups involving Latinx (N = 16) and African-American (N = 8) adults in community settings. Data were interpreted using an inductive thematic analysis. Results: Three overarching themes emerged: (1) fresh food accessibility was limited by cost, household size, and transportation but enhanced by food pantries, budgeting, and education; (2) cooking behaviors were curbed by time constraints and unfamiliarity but propagated by passion, traditions, and communal practices; and (3) health and wellness deterrents included unhealthy diets driven by cultural and familial norms; however, weight loss and awareness of comorbidities were positive motivators. Participants shared their preference for local produce and cooking classes as components of a FFRx program while raising concerns about low participation due to the stigma of receiving aid. Conclusions: Our findings illuminated interest in engaging in a FFRx program and learning ways to prepare healthy foods. A program distributing fresh produce and healthy lifestyle education could close gaps identified in African-American and Latinx communities at risk for FI.

Scaffold diversity of exemplified medicinal chemistry space.

The scaffold diversity of 7 representative commercial and proprietary compound libraries is explored for the first time using both Murcko frameworks and Scaffold Trees. We show that Level 1 of the Scaffold Tree is useful for the characterization of scaffold diversity in compound libraries and offers advantages over the use of Murcko frameworks. This analysis also demonstrates that the majority of compounds in the libraries we analyzed contain only a small number of well represented scaffolds and that a high percentage of singleton scaffolds represent the remaining compounds. We use Tree Maps to clearly visualize the scaffold space of representative compound libraries, for example, to display highly populated scaffolds and clusters of structurally similar scaffolds. This study further highlights the need for diversification of compound libraries used in hit discovery by focusing library enrichment on the synthesis of compounds with novel or underrepresented scaffolds.

Debris Flow Syndrome: Injuries and Outcomes after the Montecito Debris Flow.

On January 9, 2018, a catastrophic debris flow devastated Montecito, California. A 30-foot wall of boulders, mud, and debris ran down the hillsides at 15 miles per hour injuring dozens and causing 21 prehospital deaths. A retrospective review was conducted of the victims from the debris flow presenting to Cottage Health. Injury patterns, procedures performed, complications, length of stay, and outcomes were analyzed. Twenty-four patients were evaluated; 15 were admitted. Of the patients admitted, the most common presenting symptoms were soft tissue injuries (100%), hypothermia (67%), craniofacial injuries (67%), corneal abrasions (53%), and orthopedic injuries (47%), as well as loss of an immediate family member during the incident (73%). Procedures included skin irrigation (93%), operative soft tissue debridement (47%), body orifice irrigation due to mud impaction (40%), and orthopedic repair of fractures and ligaments (40%). All survived to discharge. "Debris flow syndrome" can be defined as a pattern of injuries, including soft tissue injuries, hypothermia, craniofacial trauma, corneal abrasions, orthopedic injuries, and mud impaction. Managing the debris flow syndrome requires co-ordinated and specialized care.

Contemporary outcomes after pericardial window surgery: impact of operative technique.

BACKGROUND: The optimal window procedure for drainage of a large pericardial effusion has yet to be established. The purpose of this study was to compare the outcomes associated with the subxiphoid and thoracotomy pericardial window techniques, with a focus on perioperative pain and effusion recurrence rates. METHODS: A retrospective single-center observational study of all pericardial window operations was performed, with the incision based on surgeon preference. Perioperative data was recorded including time to extubation, narcotic requirements, and the development of a recurrent pericardial effusion. RESULTS: From 2002 to 2015, 179 patients with a large pericardial effusion underwent either a subxiphoid (n = 127) or left anterior mini-thoracotomy (n = 52) pericardial window procedure. Patients (mean age 73.2 years, 56 % female) had a high incidence of previous malignancy (49 %), chronic anticoagulation (34 %), recent infection (26 %), or renal failure (18 %). Cardiac tamponade was present in 50 %, and 12 % had undergone previous pericardiocentesis. Comparing the two techniques, there was no difference in the amount of fluid drained or in the perioperative mortality rate. Postoperatively, patients who had the subxiphoid approach required less time before extubation (P = 0.002) and needed less narcotics within 48 h after surgery (P = 0.0001) compared to thoracotomy patients. However, patients treated with the subxiphoid technique more often developed recurrent moderate or large pericardial effusions (P = 0.02), and there was a trend towards more repeat operations needed (P = 0.15). CONCLUSION: Pericardial window surgery via a subxiphoid incision is associated with less postoperative pain and faster time to extubation. However, the thoracotomy approach may be more effective at preventing effusion recurrence and the need for repeat surgery.

Branched endograft repair of an aortic stump aneurysm.

We present a patient with an aortic stump aneurysm that was repaired with a custom-made, four-branched thoracoabdominal endograft. The repair was performed in two stages using a special delivery system designed to be introduced in an antegrade manner through a median sternotomy due to a lack of iliofemoral access. At 1 year, the patient remains in good health, with his aneurysm completely excluded and decreased in size, without migration, and all branch vessels patent. This report represents a unique endovascular repair of a complex aortic pathology in a patient without other surgical options.

Perceptions and psychosocial correlates of bullying among Lumbee Indian youth.

Although bullying has been linked to suicide among youth, little is known about bullying in American Indians, a population at high risk for suicide. Qualitative data from focus groups with Lumbee Indian youth (N = 31, 16 males, 15 females, 12-17 years of age) and in-depth interviews with gatekeepers in the Lumbee community revealed that bullying is common, and is perceived to contribute to depression and suicide. Youth expressed powerlessness to overcome bullying. Survey data (N = 79, 32 males, 47 females, 11-18 years of age) showed that bullied youth (11.5%) had lower self-esteem and higher levels of depressive symptoms. Interventions are needed to address this behavior that contributes to poor psychosocial health in Lumbee youth.

Mentoring programs for underrepresented minority faculty in academic medical centers: a systematic review of the literature.

PURPOSE: Mentoring is critical for career advancement in academic medicine. However, underrepresented minority (URM) faculty often receive less mentoring than their nonminority peers. The authors conducted a comprehensive review of published mentoring programs designed for URM faculty to identify "promising practices." METHOD: Databases (PubMed, PsycINFO, ERIC, PsychLit, Google Scholar, Dissertations Abstracts International, CINHAL, Sociological Abstracts) were searched for articles describing URM faculty mentoring programs. The RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance) formed the model for analyzing programs. RESULTS: The search identified 73 citations. Abstract reviews led to retrieval of 38 full-text articles for assessment; 18 articles describing 13 programs were selected for review. The reach of these programs ranged from 7 to 128 participants. Most evaluated programs on the basis of the number of grant applications and manuscripts produced or satisfaction with program content. Programs offered a variety of training experiences, and adoption was relatively high, with minor changes made for implementing the intended content. Barriers included time-restricted funding, inadequate evaluation due to few participants, significant time commitments required from mentors, and difficulty in addressing institutional challenges faced by URM faculty. Program sustainability was a concern because programs were supported through external funds, with minimal institutional support. CONCLUSIONS: Mentoring is an important part of academic medicine, particularly for URM faculty who often experience unique career challenges. Despite this need, relatively few publications exist to document mentoring programs for this population. Institutionally supported mentoring programs for URM faculty are needed, along with detailed plans for program sustainability.

Applying the theory of planned behavior to explore HAART adherence among HIV-positive immigrant Latinos: elicitation interview results.

OBJECTIVE: This study explored influences on intention to adhere to highly active antiretroviral therapy (HAART) among immigrant Latinos living with HIV/AIDS in the southeastern USA. METHODS: Our community-based participatory research (CBPR) partnership completed individual in-depth interviews with 25 immigrant Latinos, based on the theory of planned behavior (TPB), to explore beliefs toward HAART adherence and HIV testing. RESULTS: Participants identified (a) seven outcomes of treatment adherence (e.g., "feeling good" and "controlling the virus"), (b) six groups of persons influencing adherence (e.g., family, partner/spouse), and (c) nine impediments to adherence (e.g., appointment scheduling, side effects of treatment). Fear of deportation, perceived costs of services, and barriers to communication emerged as impediments to both HAART adherence and HIV testing. CONCLUSION: The findings suggest the utility of TPB in identifying factors to enhance HAART adherence among immigrant Latinos. Future research should explore the extent to which these identified TPB components quantitatively influence adherence intention and immunological and virological outcomes. PRACTICE IMPLICATIONS: Culturally congruent interventions for immigrant Latinos may need to focus on facilitators of adherence, influential referent groups, and destigmatizing HIV/AIDS.

Bioisosteric Replacement and Scaffold Hopping in Lead Generation and Optimization.

Bioisosteric replacement and scaffold hopping are twin methods used in drug design to improve the synthetic accessibility, potency and drug like properties of a compound and to move into novel chemical space. Bioisosteric replacement involves swapping functional groups of a molecule with other functional groups that have similar biological properties. Scaffold hopping is the replacement of the core framework of a molecule with another scaffold that will improve the properties of the molecule or to find similar potent compounds that exist in novel chemical space. This review outlines the key concepts, importance and challenges of both methods using examples and comparisons of techniques available for finding bioisosteric replacements and scaffold hops. There are many methods available for bioisosteric replacement and scaffold hopping, all with their own advantages and disadvantages. Drug design projects would benefit from a combination of these methods to retrieve diverse and complimentary results. Continuing progress in these fields will allow further validation of both methods as well as the accumulation of knowledge on bioisosteres and possible scaffold replacements.

Predicting cytotoxicity from heterogeneous data sources with Bayesian learning.

BACKGROUND: We collected data from over 80 different cytotoxicity assays from Pfizer in-house work as well as from public sources and investigated the feasibility of using these datasets, which come from a variety of assay formats (having for instance different measured endpoints, incubation times and cell types) to derive a general cytotoxicity model. Our main aim was to derive a computational model based on this data that can highlight potentially cytotoxic series early in the drug discovery process. RESULTS: We developed Bayesian models for each assay using Scitegic FCFP_6 fingerprints together with the default physical property descriptors. Pairs of assays that are mutually predictive were identified by calculating the ROC score of the model derived from one predicting the experimental outcome of the other, and vice versa. The prediction pairs were visualised in a network where nodes are assays and edges are drawn for ROC scores >0.60 in both directions. We observed that, if assay pairs (A, B) and (B, C) were mutually predictive, this was often not the case for the pair (A, C). The results from 48 assays connected to each other were merged in one training set of 145590 compounds and a general cytotoxicity model was derived. The model has been cross-validated as well as being validated with a set of 89 FDA approved drug compounds. CONCLUSIONS: We have generated a predictive model for general cytotoxicity which could speed up the drug discovery process in multiple ways. Firstly, this analysis has shown that the outcomes of different assay formats can be mutually predictive, thus removing the need to submit a potentially toxic compound to multiple assays. Furthermore, this analysis enables selection of (a) the easiest-to-run assay as corporate standard, or (b) the most descriptive panel of assays by including assays whose outcomes are not mutually predictive. The model is no replacement for a cytotoxicity assay but opens the opportunity to be more selective about which compounds are to be submitted to it. On a more mundane level, having data from more than 80 assays in one dataset answers, for the first time, the question - "what are the known cytotoxic compounds from the Pfizer compound collection?" Finally, having a predictive cytotoxicity model will assist the design of new compounds with a desired cytotoxicity profile, since comparison of the model output with data from an in vitro safety/toxicology assay suggests one is predictive of the other.

La Clínica del Pueblo: a model of collaboration between a private media broadcasting corporation and an academic medical center for health education for North Carolina Latinos.

La Clínica del Pueblo, a health education collaboration between the Maya Angelou Center for Health Equity at Wake Forest University School of Medicine and Qué Pasa Media, Inc., disseminates culturally appropriate health information to the North Carolina (NC) Latino community. The program includes a weekly radio show and corresponding newspaper column addressing four areas: childhood health, adult health, safety, and utilization. The radio show format includes a didactic presentation followed by a call-in question and answer period. Over 200 consecutive weeks of programming have been completed, averaging 11 calls per show. A Latino healthcare resource guide and hotline also provide resource information. Participant demographic information indicates that 50% of the target population comes from Mexico, 60% are women, and 70% of the community is younger than 38 years. There was an increase in the use of the media as a source of health information over the course of the project, from an initial 33% of respondents to 58% in the last survey. Listenership to La Clínica del Pueblo displayed a pronounced increase (18% initial survey to 55% in last survey, P < 0.05). We also observed a statistically significant increase in medical knowledge from initial survey to the last survey (P < 0.001). By multiple regression analysis, we identified 4 predictors of medical knowledge: order of surveys (1 < 3, P < 0.001), education level (P < 0.0001), female gender (P < 0.01) and radio listenership (P < 0.05). The first three variables predicted higher scores; however, radio listening recognition of our radio program was more common among individuals who had lower scores. In conclusion, La Clínica del Pueblo is a model for a novel approach that can reach the Latino community to improve medical knowledge and possibly affect health behaviors in a positive manner.