Evaluating the Correlation Between Anteroposterior Diameter, Body Surface Area, and Height for Liver Transplant Donors and Recipients.

Background: Small stature and female sex correlate to decreased deceased donor liver transplant (DDLT) access and higher waitlist mortality. However, efforts are being made to improve access and equity of allocation under the new continuous distribution (CD) system. Liver anteroposterior diameter (APD) is a method used by many centers to determine size compatibility for DDLT but is not recorded systematically, so it cannot be used for allocation algorithms. We therefore seek to correlate body surface area (BSA) and height to APD in donors and recipients and compare waitlist outcomes by these factors to support their use in the CD system. Methods: APD was measured from single-center DDLT recipients and donors with cross-sectional imaging. Linear, Pearson, and PhiK correlation coefficient were used to correlate BSA and height to APD. Competing risk analysis of waitlist outcomes was performed using United Network for Organ Sharing data. Results: For 143 pairs, donor BSA correlated better with APD than height (PhiK = 0.63 versus 0.20). For recipient all comers, neither BSA nor height were good correlates of APD, except in recipients without ascites, where BSA correlated well (PhiK = 0.63) but height did not. However, among female recipients, BSA, but not height, strongly correlated to APD regardless of ascites status (PhiK = 0.80 without, PhiK = 0.70 with). Among male recipients, BSA correlated to APD only in those without ascites (PhiK = 0.74). In multivariable models, both BSA and height were predictive of waitlist outcomes, with higher values being associated with increased access, decreased delisting for death/clinical deterioration, and decreased living donor transplant (model concordance 0.748 and 0.747, respectively). Conclusions: Taken together, BSA is a good surrogate for APD and can therefore be used in allocation decision making in the upcoming CD era to offset size and gender-based disparities among certain candidate populations.

The state of the art in secondary pharmacology and its impact on the safety of new medicines.

Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities has become standard practice in pharmaceutical research and development, and regulatory agencies are increasingly requesting data on activity against targets with recognized adverse effect relationships. However, the screening strategies and target panels used by pharmaceutical companies may vary substantially. To help identify commonalities and differences, as well as to highlight opportunities for further optimization of secondary pharmacology assessment, we conducted a broad-ranging survey across 18 companies under the auspices of the DruSafe leadership group of the International Consortium for Innovation and Quality in Pharmaceutical Development. Based on our analysis of this survey and discussions and additional research within the group, we present here an overview of the current state of the art in secondary pharmacology screening. We discuss best practices, including additional safety-associated targets not covered by most current screening panels, and present approaches for interpreting and reporting off-target activities. We also provide an assessment of the safety impact of secondary pharmacology screening, and a perspective on opportunities and challenges in this rapidly developing field.

Associations of street-view greenspace with Parkinson's disease hospitalizations in an open cohort of elderly US Medicare beneficiaries.

INTRODUCTION: Protective associations of greenspace with Parkinson's disease (PD) have been observed in some studies. Visual exposure to greenspace seems to be important for some of the proposed pathways underlying these associations. However, most studies use overhead-view measures (e.g., satellite imagery, land-classification data) that do not capture street-view greenspace and cannot distinguish between specific greenspace types. We aimed to evaluate associations of street-view greenspace measures with hospitalizations with a PD diagnosis code (PD-involved hospitalization). METHODS: We created an open cohort of about 45.6 million Medicare fee-for-service beneficiaries aged 65 + years living in core based statistical areas (i.e. non-rural areas) in the contiguous US (2007-2016). We obtained 350 million Google Street View images across the US and applied deep learning algorithms to identify percentages of specific greenspace features in each image, including trees, grass, and other green features (i.e., plants, flowers, fields). We assessed yearly average street-view greenspace features for each ZIP code. A Cox-equivalent re-parameterized Poisson model adjusted for potential confounders (i.e. age, race/ethnicity, socioeconomic status) was used to evaluate associations with first PD-involved hospitalization. RESULTS: There were 506,899 first PD-involved hospitalizations over 254,917,192 person-years of follow-up. We found a hazard ratio (95% confidence interval) of 0.96 (0.95, 0.96) per interquartile range (IQR) increase for trees and a HR of 0.97 (0.96, 0.97) per IQR increase for other green features. In contrast, we found a HR of 1.06 (1.04, 1.07) per IQR increase for grass. Associations of trees were generally stronger for low-income (i.e. Medicaid eligible) individuals, Black individuals, and in areas with a lower median household income and a higher population density. CONCLUSION: Increasing exposure to trees and other green features may reduce PD-involved hospitalizations, while increasing exposure to grass may increase hospitalizations. The protective associations may be stronger for marginalized individuals and individuals living in densely populated areas.

An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis.

Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitors. The age-induced megakaryocyte progenitors have a profoundly enhanced capacity to engraft, expand, restore, and reconstitute platelets in situ and upon transplantation and produce an additional platelet population in old mice. The two pools of co-existing platelets cause age-related thrombocytosis and dramatically increased thrombosis in vivo. Strikingly, aging-enriched platelets are functionally hyper-reactive compared with the canonical platelet populations. These findings reveal stem cell-based aging as a mechanism for platelet dysregulation and age-induced thrombosis.

Structural and molecular basis of choline uptake into the brain by FLVCR2.

Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification and neurotransmission. The brain has a particularly high demand for choline, but how it enters the brain remains unknown1-3. The major facilitator superfamily transporter FLVCR1 (also known as MFSD7B or SLC49A1) was recently determined to be a choline transporter but is not highly expressed at the blood-brain barrier, whereas the related protein FLVCR2 (also known as MFSD7C or SLC49A2) is expressed in endothelial cells at the blood-brain barrier4-7. Previous studies have shown that mutations in human Flvcr2 cause cerebral vascular abnormalities, hydrocephalus and embryonic lethality, but the physiological role of FLVCR2 is unknown4,5. Here we demonstrate both in vivo and in vitro that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain. We also determine the structures of choline-bound FLVCR2 in both inward-facing and outward-facing states using cryo-electron microscopy. These results reveal how the brain obtains choline and provide molecular-level insights into how FLVCR2 binds choline in an aromatic cage and mediates its uptake. Our work could provide a novel framework for the targeted delivery of therapeutic agents into the brain.

The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms. STUDY DESIGN: Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders. STUDY RESULTS: Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable. CONCLUSIONS: Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.

The rates of septicemia in older adults with prostate cancer treated with abiraterone or enzalutamide: A population-based study.

INTRODUCTION: Prostate cancer (PCa) is the most common non-cutaneous tumor among American men. Androgen receptor signaling inhibitors such as abiraterone and enzalutamide have been approved for similar disease states among patients with advanced PCa. Existing data suggest using steroids is associated with an increased risk of infection. Because abiraterone is usually prescribed with prednisone, we sought to compare the risk of septicemia in patients using abiraterone vs. enzalutamide. MATERIALS AND METHODS: We utilized the SEER-Medicare-linked data and used negative binomial regression models to compare the changes in the rates of septicemia-related hospitalizations six months pre- and post-abiraterone and enzalutamide initiation. RESULTS: We found that the incidence of septicemia-related hospitalizations increased 2.77 fold within six months of initiating abiraterone (incidence rate ratio [IRR]: 2.77, 95% confidence interval [CI]: 2.17-3.53) 1.97 fold within six months of starting enzalutamide (IRR: 1.97, 95% CI: 1.43-2.72). However, the difference in the changes did not reach statistical significance (interaction IRR: 0.71, 95% CI: 0.48-1.06). DISCUSSION: The findings suggest that both abiraterone and enzalutamide are associated with an increased risk of septicemia-related hospitalizations. However, the difference in the increase of septicemia risk following the two treatments did not reach statistical significance. Further studies are warranted to understand the mechanisms at play.

High Juvenile Mortality Overwhelms Benefits of Mating Potential for Reproductive Fitness.

AbstractAn individual's access to mates (i.e., its "mating potential") can constrain its reproduction but may also influence its fitness through effects on offspring survival. For instance, mate proximity may correspond with relatedness and lead to inbreeding depression in offspring. While offspring production and survival might respond differently to mating potential, previous studies have not considered the simultaneous effects of mating potential on these fitness components. We investigated the relationship of mating potential with both production and survival of offspring in populations of a long-lived herbaceous perennial, Echinacea angustifolia. Across 7 years and 14 sites, we quantified the mating potential of maternal plants in 1,278 mating bouts and followed the offspring from these bouts over 8 years. We used aster models to evaluate the relationship of mating potential with the number of offspring that emerged and that were alive after 8 years. Seedling emergence increased with mating potential. Despite this, the number of offspring surviving after 8 years showed no relationship to mating potential. Our results support the broader conclusion that the effect of mating potential on fitness erodes over time because of demographic stochasticity at the maternal level.

Relegated to the Sidelines: A Qualitative Inquiry of Gatekeepers' Perspectives and Values of Physical Education for Disabled Children.

Several institutional aspects within the U.S. public school system impede the delivery of adapted physical education (APE) services to disabled children, including a lack of understanding and prioritization of these services by the special education team and a lack of qualified APE professionals to deliver these services. Thus, we conducted a qualitative inquiry grounded in a critical-ableism perspective to explore special education gatekeepers' experiences and perspectives of APE. Gatekeepers included parents, physical educators, and school administrators. Using a reflexive thematic analysis, we developed four interrelated themes: (a) disregard, negative, and charity mindsets toward disability; (b) systemic challenges in valuing and prioritizing APE; (c) presence as inclusion: (un)intentional marginalization in physical education; and (d) physical education for my child was a nightmare. These findings illustrate the complexities around the provision of physical education and APE to disabled children.

Real-Time Use of a Dynamic Model To Measure the Impact of Public Health Interventions on Measles Outbreak Size and Duration - Chicago, Illinois, 2024.

Measles is a highly infectious, vaccine-preventable disease that can cause severe illness, hospitalization, and death. A measles outbreak associated with a migrant shelter in Chicago occurred during February-April 2024, in which a total of 57 confirmed cases were identified, including 52 among shelter residents, three among staff members, and two among community members with a known link to the shelter. CDC simulated a measles outbreak among shelter residents using a dynamic disease model, updated in real time as additional cases were identified, to produce outbreak forecasts and assess the impact of public health interventions. As of April 8, the model forecasted a median final outbreak size of 58 cases (IQR = 56-60 cases); model fit and prediction range improved as more case data became available. Counterfactual analysis of different intervention scenarios demonstrated the importance of early deployment of public health interventions in Chicago, with a 69% chance of an outbreak of 100 or more cases had there been no mass vaccination or active case-finding compared with only a 1% chance when those interventions were deployed. This analysis highlights the value of using real-time, dynamic models to aid public health response, set expectations about outbreak size and duration, and quantify the impact of interventions. The model shows that prompt mass vaccination and active case-finding likely substantially reduced the chance of a large (100 or more cases) outbreak in Chicago.

Longitudinal Analysis and Latent Growth Modeling of the Modified Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR).

The Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR) was developed as a short-form survey to measure progress after total hip arthroplasty (THA). However, the longitudinal validity of the scale structure pertaining to the modified five-item HOOS-JR has not been assessed. Therefore, the purpose of this study was to evaluate the structural validity, longitudinal invariance properties, and latent growth curve (LGC) modeling of the modified five-item HOOS-JR in a large multi-site sample of patients who underwent a THA. A longitudinal study was conducted using data from the Surgical Outcome System (SOS) database. Confirmatory factor analyses (CFAs) were conducted to assess the structural validity and longitudinal invariance across five time points. Additionally, LGC modeling was performed to assess the heterogeneity of the recovery patterns for different subgroups of patients. The resulting CFAs met most of the goodness-of-fit indices (CFI = 0.964-0.982; IFI = 0.965-0.986; SRMR = 0.021-0.035). Longitudinal analysis did not meet full invariance, exceeding the scalar invariance model (CFIDIFF = 0.012; χ2DIFF test = 702.67). Partial invariance requirements were met upon release of the intercept constraint associated with item five (CFIDIFF test = 0.010; χ2DIFF = 1073.83). The equal means model did not pass the recommended goodness-of-fit indices (CFIDIFF = 0.133; χ2DIFF = 3962.49). Scores significantly changed over time, with the highest scores identified preoperatively and the lowest scores identified at 2- and 3-years postoperatively. Upon conclusion, partial scalar invariance was identified within our model. We identified that patients self-report most improvements in their scores within 6 months postoperatively. Females reported more hip disability at preoperative time points and had faster improvement as measured by the scores of the modified five-item HOOS-JR.

Longitudinal Trajectories of Premorbid Social and Academic Adjustment in Youth at Clinical High Risk for Psychosis: Implications for Conversion.

BACKGROUND AND HYPOTHESIS: Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the between-person level, which has constrained analyses of premorbid adjustment, clinical covariates, and conversion to psychosis. STUDY DESIGN: Growth-curve models examined longitudinal trajectories in retrospective reports of premorbid social and academic adjustment from youth at CHR (n = 498). Interaction models tested whether known covariates of premorbid adjustment problems (attenuated negative symptoms, cognition, and childhood trauma) were associated with different premorbid adjustment trajectories in converters vs non-converters (ie, participants who did/did not develop psychotic disorders within 2-year follow-up). STUDY RESULTS: Converters reported poorer social adjustment throughout the premorbid period. Converters who developed psychosis with an affective component reported poorer academic adjustment throughout the premorbid period than those who developed non-affective psychosis. Tentatively, baseline attenuated negative symptoms may have been associated with worsening social adjustment in the premorbid period for non-converters only. Childhood trauma impact was associated with fewer academic functioning problems among converters. Cognition effects did not differ based on conversion status. CONCLUSIONS: Premorbid social function is an important factor in risk for conversion to psychosis. Negative symptoms and childhood trauma had different relationships to premorbid functioning in converters vs non-converters. Mechanisms linking symptoms and trauma to functional impairment may be different in converters vs non-converters, suggesting possible new avenues for risk assessment.

The Italian adaptation of the Mini-SIPS, a tool for early detection of individuals at clinical high risk and first episode of psychosis: A preliminary study of implementation in an Italian FEP program.

AIMS: The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. METHODS: The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high risk (CHR) framework, the DSM-5 Attenuated Psychosis Syndrome (APS) and to be implemented in clinical settings. The Mini-SIPS was translated in Italian by a Yale-certified SIPS trainer, then back-translated in English by a trained psychologist, then approved by the Mini-SIPS authors. Since September 2021, the adapted Italian version of the Mini-SIPS has been implemented at the First Episode Psychosis (FEP) Program in Ferrara, Italy. RESULTS: The Italian version of Mini-SIPS was successfully administered to 15 individuals subsequently referred to the First Episode Psychosis service in Ferrara. Within this sample, the tool has proven to be both an effective and efficient tool for the identification of CHR and FEP, and a valid instrument to help with the differential diagnosis. It also performed as a valuable guide for retrieving information about psychiatric history, to date the onset of APS and/or full-blown psychosis, to track the progression from CHR to psychosis or to symptoms resolution and to describe patients' pathways to care. CONCLUSION: The Mini-SIPS is an efficient and easy-to-use interview to identify the early stages of psychosis and established psychosis in clinical contexts. The Italian adaptation of this interview could be effectively implemented in other Italian FEP Programs as a screening and monitoring tool. Formal validation of the instrument is needed to assessed validity and reliability in the diagnosis of the CHR and FEP.

Geographical Variation In Medication and Health Resource Use In Multiple Sclerosis.

BACKGROUND: Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care. METHODS: Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied. RESULTS: Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied. CONCLUSIONS: Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

A novel approach to assess temporal baseline levels of trace metal contamination in the mussel M. galloprovincialis in the Mediterranean, Marmara and Black Seas.

This study reports, for the first time, the baseline levels for fifteen trace metals in M. galloprovincialis tissue from around the Mediterranean, Marmara and Black Seas. The environmental quality in the surrounding seawater was assessed i.e., a mussel farm was investigated by using CF and DC indices, and the water quality was qualified as good for the aquacultural activities. A strong Cu-regulation in the transplanted mussels was observed and it ranged between 3.20 and 3.60 µg/g d.w. The highest bioavailability and bioconcentration of the particulate Fe fraction could present a health risk to consumers with a low risk level (1 < THQ < 9.9). Cr is considered the limiting metal for mussel consumption (< 2 kg/day). The metal contamination gradient was assessed using TEPI and TESVI indices that identified seven reference stations on the large scale and revealed that Cd is the most investigated metal in the literature databases, and found that Pb was the most bioavailable contaminant in the areas examined.

Society of Radiologists in Ultrasound Consensus on Routine Pelvic US for Endometriosis.

Endometriosis is a prevalent and potentially debilitating condition that mostly affects individuals of reproductive age, and often has a substantial diagnostic delay. US is usually the first-line imaging modality used when patients report chronic pelvic pain or have issues of infertility, both common symptoms of endometriosis. Other than the visualization of an endometrioma, sonologists frequently do not appreciate endometriosis on routine transvaginal US images. Given a substantial body of literature describing techniques to depict endometriosis at US, the Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts to make recommendations aimed at improving the screening process for endometriosis. The panel was composed of experts in the imaging and management of endometriosis, including radiologists, sonographers, gynecologists, reproductive endocrinologists, and minimally invasive gynecologic surgeons. A comprehensive literature review combined with a modified Delphi technique achieved a consensus. This statement defines the targeted screening population, describes techniques for augmenting pelvic US, establishes direct and indirect observations for endometriosis at US, creates an observational grading and reporting system, and makes recommendations for additional imaging and patient management. The panel recommends transvaginal US of the posterior compartment, observation of the relative positioning of the uterus and ovaries, and the uterine sliding sign maneuver to improve the detection of endometriosis. These additional techniques can be performed in 5 minutes or less and could ultimately decrease the delay of an endometriosis diagnosis in at-risk patients.

Description and taxonomic assessment of fossil Cercopithecidae from the Pliocene Galili Formation (Ethiopia).

The Mount Galili Formation in the Afar region, Ethiopia, samples a critical time in hominin evolution, 4.4 to 3.8 Ma, documenting the last appearance of Ardipithecus and the origin of Australopithecus. This period is also important in the evolution of cercopithecids, especially the origin of Theropithecus in general and Theropithecus oswaldi lineage in particular. Galili has provided a total of 655 cercopithecid specimens that include crania, mandibles, isolated teeth and postcrania. All the fossils were recovered from the Lasdanan (5.3-4.43 Ma), Dhidinley (4.43-3.9 Ma) and Shabeley Laag (∼3.92-3.8 Ma) Members. Here, we described and analyzed 362 fossils employing both qualitative and quantitative methods. Descriptions of the material were supplemented with dental metrics and cranial shape analysis using three-dimensional geometric morphometrics. Results indicate the presence of at least six cercopithecid taxa: Theropithecus oswaldi serengetensis (n = 28), Theropithecus sp. (n = 2), three non-Theropithecus papionin groups (n = 134) and one colobine-size group (n = 58). The T. o. serengetensis represents the earliest form of the lineage, documented from ∼3.9 Ma Galili sediments. The three Galili papionins include a smaller taxon, a medium-sized taxon comparable to Pliopapio alemui and a large papionin overlapping in size with Soromandrillus, Gorgopithecus and Dinopithecus. The majority of Galili colobines have closest affinities to Kuseracolobus aramisi and some overlap with other taxa. Papionins dominate the Galili cercopithecid collection, although colobines are still fairly common (approximately 25% of the sample). Thus, Galili sample is like Kanapoi (4.2-4.1 Ma) and Gona (5.2-3.9 Ma) localities but distinct from Aramis, suggesting paleoecological similarity to the former sites. On the other hand, Theropithecus is less abundant at Galili than geologically younger Hadar (3.4-3.2 Ma) and Woranso-Mille (3.8-3.6 Ma) sites. Whether this difference is due to sampling, time or landscape variation requires further investigation.

"Working me to life" - Longitudinal Perceptions from Adults with Heart Failure with Preserved Ejection Fraction Enrolled in an Exercise Training Clinical Trial.

AIMS: Adults with heart failure with preserved ejection fraction (HFpEF) responded more favorably to an exercise intervention compared to those with reduced ejection fraction. This study explores factors that contributed to this response focusing on the qualitative perceptions of adults with HFpEF enrolled in an exercise intervention. METHODS AND RESULTS: This qualitative descriptive study is a secondary analysis of longitudinal interviews collected at 3, 6, 12, and 18-months from participants with HFpEF enrolled in a randomized controlled trial testing an intervention to promote adherence to exercise. We included participants with at least 2 interviews. Interviews were examined across and within participants and time points using thematic analysis. Analyses included 67 interviews from 21 adults with HFpEF enrolled in the intervention arm. The sample was 52% (11/21) male and over 47% (10/21) non-White. Mean age at enrollment was 63.7 ± 9.9 years. We identified 4 major themes: 1. Overcoming negative attitudes, barriers, and injury, 2. Motivations to exercise, 3. Exercise - the panacea for HFpEF symptoms and quality of life, and 4. Advice for others with HFpEF. CONCLUSIONS: Our findings suggest that for many adults with HFpEF, initial hesitancy, fear, and negative attitudes about exercise can be overcome. Exercise coaching using social cognitive constructs, medical fitness center memberships, and heart rate self-monitoring are successful strategies of engaging adults with HFpEF in long-term unsupervised exercise training. REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01658670.