Small molecular weight epigenetic inhibitors modulate the extracellular matrix during pancreatic acinar ductal metaplasia.

The pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment is distinguished by a high degree of fibrosis and inflammation, known as desmoplasia. Desmoplasia increases the stromal deposition and extracellular matrix (ECM) stiffness observed in the tumor microenvironment, contributing to the dampened penetration of pharmacological agents. The molecular and biophysical composition of the ECM during the earliest cellular changes in the development of PDAC, i.e. acinar ductal metaplasia (ADM), has not been extensively explored. We report that the mRNA expression of key protein components of the ECM increases during ADM in p48Cre/+;LSL-KrasG12D (KC) mouse acinar organoids cultured in Matrigel. Treatment of the organoids with small molecular weight epigenetic modulating compounds that inhibit or reverse ADM (largazole, FK228 and chaetocin) dramatically reduced the tissue mRNA expression of collagens, hyaluronan synthase, laminin and fibronectin. The storage moduli, determined by video tracking of fluorescent nanoparticles embedded into the Matrigel, increased during ADM and was reduced following treatment with the epigenetic modulating compounds. We report that the ECM of mouse organoids stiffens during ADM and is further enhanced by the presence of mutant Kras. Moreover, select HDAC and HMT inhibitors reduced the mRNA expression of ECM components and ECM stiffness during inhibition and reversal of ADM, suggesting that these compounds may be useful as adjuvants to enhance the tumor penetration of agents used to treat PDAC.

Promise of Composite Pain Index as a single pain outcome for sickle cell disease across the lifespan.

BACKGROUND: This study aimed to validate a Composite Pain Index (CPI) as a single pain outcome measure for sickle cell disease (SCD) across the lifespan from 8 years of age. PROCEDURE: This prospective, cross-sectional study included 55 participants with SCD who completed the PAINReportIt tool and Adolescent Pediatric Pain Tool (APPT) in random order during outpatient visits to derive respective CPI scores for comparison. RESULTS: Of the 55 participants with SCD, 46 (84%) had HgbSS, eight (15%) HgbSC, and one (2%) HgbSß0+. The mean age of all participants was 17.5 ± 2.6 years, and 28 (51%) were female, 52 (95%) were Black, 42 (98%) were non-Hispanic, and 39 (71%) had a ninth grade or higher education. Correlation analyses between the APPT and PAINReportIt revealed positive associations for the number of pain sites (r = .57, p < .001), pain intensity (r = .46, p < .001), pain quality (r = .74, p < .001), and pain pattern (r = .34, p = .01). Patients' mean CPI scores derived from the PAINReportIt was slightly higher than the APPT; 34.2 (SD = 14.7) and 30.0 (SD = 19.0), respectively. Regression analyses showed that the APPT CPI significantly predicted the PAINReportIt CPI (B = .497, t(53) = 6.051, p < .001). This finding holds true even when accounting for the order of measurement or patient's age. CONCLUSION: The initial validation of CPI as a single pain outcome measure represents a significant advancement in pain assessment for SCD. Further validation is warranted for the CPI as a measure is for both clinicians and researchers to enable longitudinal pain assessment from age 8 years across the lifespan as children age into adult care.

Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE2 face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic. This article compared the three methods to identify the best platform for training URM students in cancer disparity research. The program's effectiveness was measured through motivation, experiences, and knowledge gained by trainees during and one year after the completion of the program. The results showed that the participants were highly positive in their feedback about the professional and academic values of the program. Although the virtual and hybrid methods experienced significant challenges during the pandemic, the hybrid training module offered an "above average" effectiveness in performance, like the face-to-face mentoring platform in mentoring URM students in cancer disparity research.

John Henryism-racial stressors among older black men with low back pain.

The relationship between adaptive pain-coping skills, such as John Henryism, and pain and function remains unclear in non-Hispanic Black populations. This cross-sectional, observational study included sixty older Black men with low back pain in Jacksonville, Florida. Key measures were: self-reported 0-10 pain intensity in the past 24 h, 13-item pain catastrophizing, functional performance from the Back Performance Scale, and the John Henryism Active Coping Scale. Structural equation modeling was applied to 57 complete cases for analysis using R v4.2.0. There was a significant association for both John Henryism (ß = -0.320, p = .038) and pain catastrophizing (ß = 0.388, p = .007) with pain intensity but not functional performance (ß = -0.095, p = .552; ß = 0.274, p = .068, respectively) in the older Black men. The study underscores the future importance of evaluating John Henryism using longitudinal methods to explore causality with complex structural equation models among Black Americans.

Dysphagia in patients with sickle cell disease: An understudied problem.

Dysphagia which is defined as disordered swallowing is well known as one of the most common and dangerous symptoms of many diseases, including neurological disorders such as Parkinson's disease, amyotrophic lateral sclerosis, myasthenia gravis, and most commonly, stroke. Strokes are a potentially devastating complication of sickle cell disease (SCD), the most common genetic hemoglobinopathy worldwide, yet little is known about dysphagia as it relates to SCD. Thus, the purposes of this article are to review briefly the primary causes and health consequences of dysphagia, to highlight the relevance of dysphagia to SCD, to review what little is known about dysphagia in SCD, to recommend, based on our consensus and the available literature, when to screen, evaluate, and monitor dysphagia in patients with SCD, and to outline unanswered questions where research on dysphagia in SCD might improve health outcomes.

Factors and topics associated with empathic self-disclosure in dignity therapy of cancer patients.

Objective: During Dignity Therapy a trained provider guides a patient to share their life story and legacy. Providers can demonstrate empathy through empathic self-disclosure (ESD), sharing something substantial and personal about themselves in response to the patient. The current study aims to identify the topics of ESDs and determine whether ESD frequency varied by patient and/or provider characteristics. Methods: Two coders analyzed 203 audio-recorded, transcribed Dignity Therapy sessions of palliative care patients (M = 65.78 years; SD = 7.43 years, 65.69% women) for ESD. Topic modeling characterized themes of ESD and multilevel modeling examined ESD frequency based on several patient and provider characteristics. Results: ESD occurred in 37% of interviews (M = 0.59, SD = 1.21). Topic modeling revealed five main themes: family, memory, school, geographical experiences, and values/beliefs. Multilevel modeling indicated patient-level differences, including greater rates of ESD when patients were men and older. Conclusion: ESD seems to be dependent on the context of the patient rather than individual communication style differences. Providers may use ESD in multiple instances, including when similar and different from patients. Innovation: This study introduces and defines the novel concept of ESD. It is among the first to examine patient-provider communication during Dignity Therapy, and the first to specifically examine self-disclosure.

Social network analysis of the CaRE2 health equity center: Team science in full display.

Cancer health disparities that exist in the Black or African American and Hispanic or Latino/x communities are scientific challenges, yet there are limited team science approaches to mitigate these challenges. This article's purpose is to evaluate the team science collaborations of the National Institutes of Health-funded Florida-California Cancer Research, Education & Engagement (CaRE2 ) Center partnership underscoring the inclusion of multidisciplinary team members and future under-represented minority (URM) cancer researchers. To understand our collaborative efforts, we conducted a social network analysis (SNA) of the CaRE2 Center partnership among University of Florida, Florida A&M University, and University of Southern California with data collected via the dimensions.ai application programming interface. We downloaded metadata for all publications associated with dimensions.ai IDs. The CaRE2 collaboration network increased over time as evidenced by accruing more external collaborators and more publishing of collaborative works. Degree centrality of key personnel was stable in each wave of the networks. CaRE2 key personnel averaged a total of 60.8 collaborators in 2018-2019 (SD = 57.4, minimum = 3, maximum = 221), and 65.8 collaborators in 2020-2021 (SD = 56.06, minimum = 4, maximum = 222). Betweenness was largely stable across all groups and waves. We observed a steady decline in transitivity, the probability that a pair of CaRE2 co-authors shared a third co-author, from 0.74 in 2018 to 0.47 in 2022. The SNA findings suggest that the CaRE2 Center partnership's publications show growth in team science collaborations with the inclusion of multidisciplinary team members from the three partner institutions and future URM cancer researchers who were mentored as trainees and early-stage investigators.

Voices of Black men: reflecting on prostate cancer survivorship care plans.

PURPOSE: This study addresses the critical issue of survivorship care for Black prostate cancer survivors. The aim was to explore their awareness of survivorship care plans to improve prostate cancer care and survivorship within this high-risk group. METHODS: Utilizing a thematic analysis approach, we conducted in-depth interviews focused on analyzing post-treatment experiences of Black prostate cancer survivors by applying interpretive explanations to data collected from participants. RESULTS: Participants reported a significant gap in survivorship care plan communication post-treatment, as these plans were seldom discussed. Survivors highlighted the adoption of post-treatment strategies and self-education as means to enhance their comprehension of the survivorship process. Black survivors demonstrated an intrinsic motivation, after feeling "discarded," to find suitable resources to enhance their survivorship care for a better quality of life. CONCLUSION: The prioritization of post-treatment care for Black prostate cancer survivors is important. By offering comprehensive post-treatment education, improving symptom transparency, and establishing safe spaces for open discussion, the quality of life of Black survivors may be substantially improved. IMPLICATIONS FOR CANCER SURVIVORS: There is a pressing need for dynamic post-treatment care coordination tailored to Black prostate cancer survivors. A lack of crucial post-treatment education for this population that experiences disproportionate burden of prostate cancer may exacerbate cancer health disparities. Addressing this care coordination gap may improve support systems, survivor well-being, and better cancer outcomes.

Examining Moderation of Dignity Therapy Effects by Symptom Burden or Religious/Spiritual Struggles.

CONTEXT: Dignity therapy (DT) is a well-researched psychotherapeutic intervention but it remains unclear whether symptom burden or religious/spiritual (R/S) struggles moderate DT outcomes. OBJECTIVE: To explore the effects of symptom burden and R/S struggles on DT outcomes. METHODS: This analysis was the secondary aim of a randomized controlled trial that employed a stepped-wedge design and included 579 participants with cancer, recruited from six sites across the United States. Participants were ages 55 years and older, 59% female, 22% race other than White, and receiving outpatient specialty palliative care. Outcome measures included the seven-item dignity impact scale (DIS), and QUAL-E subscales (preparation for death; life completion); distress measures were the Edmonton Symptom Assessment Scale (ESAS-r) (symptom burden), and the Religious Spiritual Struggle Scale (RSS-14; R/S). RESULTS: DT effects on DIS were significant for patients with both low (P = 0.03) and moderate/high symptom burden (P = 0.001). They were significant for patients with low (P = 0.004) but not high R/S struggle (P = 0.10). Moderation effects of symptom burden (P = 0.054) and R/S struggle (P = 0.52) on DIS were not significant. DT effects on preparation and completion were not significant, neither were the moderation effects of the two distress measures. CONCLUSION: Neither baseline symptom burden nor R/S struggle significantly moderated the effect of DT on DIS in this sample. Further study is warranted including exploration of other moderation models and development of measures sensitive to effects of DT and other end-of-life psychotherapeutic interventions.

Adherence to a reproductive health intervention for young adults with sickle cell.

BACKGROUND: The CHOICES intervention is tailored specifically for young adults with sickle cell disease (SCD) or sickle cell trait (SCT). The face-to-face (F2F) delivery format is feasible with efficacy for improving knowledge about reproductive health for those with SCD or SCT. PURPOSE: The purpose of the study was to compare the participant adherence to a remote online CHOICES intervention study (N = 107) and a F2F CHOICES intervention study (N = 234). METHODOLOGY: In both studies, participants with SCD or SCT were randomized into experimental or usual care control groups. Descriptive statistics were collected for all participants by group in both studies. Adherence was measured by retention at each data collection time point. Independent t-tests were conducted to compare mean participant adherence of the F2F and online studies postbaseline (6, 12, 18, and 24 months). RESULTS: There was a significant difference in mean adherence postbaseline between the studies (p = .005). The results suggest that more research is necessary for proper online participant retention. CONCLUSION: Advance practice nurses that are well informed on CHOICES can transmit the availability of this evidence-based intervention to this special population. Special referral for the CHOICES intervention, which is tailored specifically for young adults with SCD or SCT, may increase adherence to the intervention if it comes from trusted health care providers. IMPLICATIONS: Nurse practitioners are educators in primary and acute care settings. Encounters with reproductive age populations with SCD or SCT can occur in both settings.

Medication Engagement, Determinants of Health, and A1C Levels Among Adults With Type 2 Diabetes within a Tribal Health System.

PURPOSE: The purpose of this study was to examine the association between determinants of health, medication engagement, and A1C levels in adults with type 2 diabetes (T2DM) receiving Tribal health and pharmacy services. METHODS: A retrospective analysis of 2020-2021 electronic health record data was conducted and included adult patients with T2DM using Choctaw Nation Health Services Authority prescribed ≥1 noninsulin glucose-lowering medication in 2020, had ≥1 A1C value in 2020 and 2021, and had a valid zip code in 2021. Patients receiving both insulin and other noninsulin glucose-lowering medication were included. The proportion of days covered (PDC) was used to calculate medication engagement. Statistical analyses included bivariate analysis and linear regression. RESULTS: There were 3787 patients included in the analyses; 62.5% were considered engaged (PDC ≥ 0.8). The mean 2020 A1C level was 8.0 (64 mmol/mol) ± 1.8; 33% had an A1C of <7%, 42% had an A1C of 7% to 9%, and 25% had an A1C >9%. The mean A1C in 2021 was 7.9 (63 mmol/mol) ± 1.7; 34% had an A1C of <7%, 44% had an A1C of 7% to 9%, and 22% had an A1C >9%. Older age was weakly correlated with higher engagement; higher engagement was associated with lower A1C levels while adjusting for covariates. CONCLUSIONS: Medication engagement was associated with lower A1C levels, and older age was weakly associated with higher engagement to noninsulin glucose-lowering medications, consistent with previous literature. No determinants of health were significantly associated with A1C levels while adjusting for covariates.

Barriers and Facilitators to Integrating Acupuncture into the U.S. Health Care System: A Scoping Review.

Background: Acupuncture is a widely practiced complementary and integrative health modality that has multiple clinical applications. The use of acupuncture in the United States is rapidly increasing. Although studies have shown the efficacy and effectiveness of acupuncture for various ailments, the integration of acupuncture into the U.S. health care system remains a challenge. Little is known about the factors affecting this integration. Objective: To provide a systematic review of the barriers and facilitators affecting the integration of acupuncture into the U.S. health care system. Methods: Four electronic databases were searched. Three independent reviewers were involved in the screening and data charting processes. Findings were synthesized and categorized into four levels based on the Social Ecological Model. Results: A total of 22 studies were included in the final review. The barriers and facilitators affecting the integration of acupuncture were mapped into four levels (individual, interpersonal, organizational, and policy). The most frequently reported barriers and facilitators were mapped into the Social Ecological Model constructs within the "Individual" level (i.e., beliefs and attitudes of acupuncture, and practical issues) and the "Organizational" level (i.e., credentialing, space and facility, referral system). Conclusion: This review has identified and synthesized the breadth of evidence on the barriers and facilitators to the integration of acupuncture into the U.S. health care system. Results of this review will guide future implementation studies to develop and test implementation strategies to integrate acupuncture into the U.S. health care system.

Children's and adolescents' descriptors of asthma symptoms: An integrative review.

Background: Accurate assessment of asthma symptoms is central to appropriate treatment and management; however effective communication about symptoms-how it is perceived and reported-remain challenging in pediatric clinical and research settings. Objective: To synthesize the existing pediatric literature on children's and adolescents' word descriptors of asthma symptoms. Methods: In this integrative review, we systematically searched Cumulative Index of Nursing and Allied Health Literature and PubMed databases to identify original research studies from 1980 to 2021 on children and adolescents' word descriptors of asthma symptoms. Results: The search yielded 2,232 articles, of which 21 studies met the eligibility criteria. Scientific literature focused on children and adolescents' descriptions of asthma symptoms are limited. In addition to standard asthma symptom terminology (e.g. cough, wheeze, chest tightness, shortness of breath), pediatric populations used nonstandard word choices to describe the asthma symptom experience. Children and adolescents used a variety of affective (e.g. 'helpless', 'afraid of dying') and sensory words (e.g. 'pressure in chest', 'tightness, lungs feel shut') to describe the phenomena. Literature examining race differences in word descriptors in pediatrics is limited; thus it is unclear if word descriptors vary by race or ethnicity. Evidence of relationships between descriptors and gender and age are also lacking. Conclusions: Our review elucidates gaps in the literature regarding the full extent of the language common to racially and ethnically diverse samples of children and adolescents. Further research is warranted to help clinicians and researchers query children and adolescents' experience of asthma symptoms.