Miami VA Healthcare System

Translation elongation is a universally conserved step in protein synthesis, relying on elongation factors that engage the ribosomal L7/L12 stalk to mediate aminoacyl-tRNA delivery, accommodation, and ribosomal translocation. Using in organello cryo-electron microscopy, we reveal how the mitochondrial translation accelerator TACO1 promotes efficient elongation on human mitoribosomes. TACO1 binds the mitoribosomal region typically bound by elongation factor Tu (mtEF-Tu), bridging the large and small subunits via contacts with 16S rRNA, bL12m, A-site tRNA, and uS12m. While active throughout elongation, TACO1 is especially critical when translating polyproline motifs. Its absence prolongs mtEF-Tu residence in A/T states, causes persistent mitoribosomal stalling and premature subunit dissociation. Structural analyses indicate that TACO1 competes with mtEF-Tu for mitoribosome binding, stabilizes A-site tRNA, and enhances peptidyl transfer through a mechanism distinct from EF-P and eIF5A. These findings suggest that bacterial TACO1 orthologs may serve analogous roles, highlighting an evolutionarily conserved strategy for maintaining elongation efficiency during challenging translation events.

Background/Objectives: Post-coronavirus syndrome (long-COVID) refers to a multi-systemic range of symptoms that follows acute SARS-CoV-3 infection. Long-COVID has been linked with autonomic neuropathy as well as dry-eye disease (DED), an umbrella term that includes a variety of ocular symptoms and signs. Despite these associations, little is known about the co-occurrence of DED and dysautonomia symptoms in individuals with long-COVID. This study aims to examine relationships between dysautonomia and ocular symptoms in a long-COVID patient population. Methods: Cross-sectional study of 162 veterans with long-COVID. The Composite Autonomic Symptom Score-31 (COMPASS-31) assessed dysautonomia symptoms, and the NASA lean test and heart-rate variability metrics captured dysautonomia signs. Dry-eye disease (DED) symptoms were measured with the 5-Item Dry-Eye Questionnaire (DEQ5) and the Ocular Surface Disease Index (OSDI), while ocular pain intensity and neuropathic pain descriptors were evaluated using a Numerical Rating Scale (NRS) and select questions from the Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), respectively. Results: Most participants (78%) reported DED symptoms (DEQ5 ≥ 6). Nearly all COMPASS-31 domains were associated with DED symptoms, with the strongest correlation observed between the OSDI and pupillomotor scores (r = 0.67, p < 0.001). Among the autonomic signs, the strongest associations were observed between the change in systolic and diastolic blood pressure from baseline to 8 min and ocular pain triggered by temperature (r = -0.44 and r = -0.48, respectively, p < 0.01 for both). On linear regression analyses, pupillomotor and secretomotor symptoms remained positively associated with DED symptoms, while autonomic signs were most closely related to ocular pain metrics, with fluctuating blood pressure changes during orthostasis relating to neuropathic symptoms. Conclusions: DED symptoms, including ocular pain intensity, relate to autonomic symptoms in a long-COVID cohort. While associations with autonomic signs were less consistent, these data suggest that subtle autonomic variability relates to ocular pain in the long-COVID setting.

Caregivers' self-perceived preparedness for caregiving influences care recipients' and caregivers' emotional health, and care recipients' aging in place. Dementia's unique, long, and progressive nature compared to other age-related illnesses, along with associated behavioral symptoms and personality changes, may cause caregivers' preparedness to vary significantly from that of those caring for patients with other chronic conditions. This study aimed to describe and compare specific domains and tasks in which family caregivers of veterans with and without dementia reported wanting to be better prepared. Using the Veterans Affairs' HERO CARE (Home Excellence Resource Outcome Center to Advance, Redefine, and Evaluate Non-Institutional Care) Survey data, we analyzed caregivers' responses to one open-ended question: "Out of all the tasks that you help the veteran with, is there anything specific you would like to be better prepared for?" Response themes were deductively coded into 9 domains, and differences in reported domains between caregivers of care recipients with and without dementia were compared. A total of 732 caregivers were included: 301 (41.1%) caregivers of veterans with dementia and 431 (58.9%) without. Caregivers of veterans with and without dementia, respectively, were similar except in age, being spousal caregivers, working at least part-time, hours of care provision per week, and proportion with a high burden. Veterans with dementia, versus without, were older and had higher frailty and risk scores. Preparedness concerns among caregivers (N=732) included care coordination (n=164, 22.4%), emotional and social support (n=145, 19.8%), advance planning (n=116, 15.8%), nursing and health monitoring (n=94, 12.8%), personal care (n=65, 8.9%), mobility (n=79, 10.8%), household (n=58, 7.9%), caregiver self-care (n=36, 4.9%), and emergent situations (n=28, 3.8%). The commonest tasks caregivers expressed needs for included managing emotional and behavioral symptoms (n=74, 10.1%), recognizing and responding to significant changes in the veterans' condition (n=66, 9.0%), seeking medical information relevant to the veterans' needs (n=54, 7.4%), handling financial and legal matters (n=52, 7.1%), and advocating for services (n=49, 6.7%). Similar proportions of caregivers of veterans with and without dementia reported preparedness needs in all domains and tasks. The preparedness needs of caregivers of veterans with and without dementia were mostly similar in most domains and tasks. The commonest preparedness gaps were in the domains of care coordination, emotional and social support, and advance planning. The findings can inform interventions to prepare all caregivers to support aging in place.

Translation elongation is a universally conserved step in protein synthesis, relying on elongation factors that engage the ribosomal L7/L12 stalk to mediate aminoacyl-tRNA delivery, accommodation, and ribosomal translocation. Using in organello cryo-electron microscopy, we reveal how the mitochondrial translation accelerator TACO1 promotes efficient elongation on human mitoribosomes. TACO1 binds the mitoribosomal region typically bound by elongation factor Tu (mtEF-Tu), bridging the large and small subunits via contacts with 16S rRNA, bL12m, A-site tRNA, and uS12m. While active throughout elongation, TACO1 is especially critical when translating polyproline motifs. Its absence prolongs mtEF-Tu residence in A/T states, causes persistent mitoribosomal stalling and premature subunit dissociation. Structural analyses indicate that TACO1 competes with mtEF-Tu for mitoribosome binding, stabilizes A-site tRNA, and enhances peptidyl transfer through a mechanism distinct from EF-P and eIF5A. These findings suggest that bacterial TACO1 orthologs may serve analogous roles, highlighting an evolutionarily conserved strategy for maintaining elongation efficiency during challenging translation events.

Abstract Early-stage, formative solicitation of stakeholder needs and preferences can inform curriculum development that is responsive and fosters a sense of co-ownership. Clinical discipline preceptors are key collaborators in the ultimate implementation of an interprofessional core curriculum in geriatrics with their respective health professions trainees. This presentation describes the formative environmental scan and subsequent stakeholder engagement process to identify 1) core geriatric knowledge needed by interprofessional trainees, 2) gaps in geriatric education across discipline-specific programs, and 3) perceived barriers and delivery/modality preferences. The Geriatric Interprofessional Core Curriculum development team conducted an environmental scan to identify existing interprofessional core curricula that provide essential knowledge in best practices for caring for older adults. The team identified multiple relevant and validated resources and iteratively discussed strengths and limitations of each. Few were sufficiently inclusive to meaningfully engage the range of disciplines and levels of professional preparation represented in the GRECC health professions training program. The Geriatric 5M’s Framework (What Matters, Mentation, Medication, Mobility, Multicomplexity) provided an interprofessional scaffold that, with preceptors’ subject matter expertise, facilitated curriculum development. Accordingly, five roundtable discussions were held, each focusing on one of the 5Ms. A total of 49 interprofessional educators were engaged and asked to identify core geriatric training needs, discuss preferred curriculum modality and potential barriers to implementation. Thematic analysis of transcripts and detailed session notes yielded a set of priority content topics, as well as implementation preferences regarding usable formats and delivery, in support of the next phase of the development process.

Abstract Disclosure: R.R. Savian: None. L. Zheng: None. R.J. Galindo: None. G. Arevalo: None. J. Paris: None. V.S. Lagari-Libhaber: None. Background: Fibrous dysplasia (FD) is a rare mosaic skeletal disorder characterized by replacement of normal bone with fibro-osseous tissue. It presents as monostotic or polyostotic disease and may co-occur with hyperfunctioning endocrinopathies and café-au-lait macules in McCune-Albright syndrome (MAS). Despite established guidelines, longitudinal data on clinical outcomes and specialty follow-up in adult FD populations remain limited. Methods: We conducted a retrospective review of adults with FD evaluated at the University of Miami, a tertiary referral center, between 2014 and 2024. Of 540 patients initially identified by ICD coding, 102 were included based on availability of complete and verifiable clinical data. The cohort included a large number of Hispanic patients, offering unique insight into the burden of a rare skeletal disorder in an underrepresented population. Disease subtype, endocrine manifestations, skeletal complications, biochemical profiles, treatment approaches, and specialty follow-up were assessed. Results: Among 102 patients (mean age 50.1 ± 18.7 years), 62.7% were female. Polyostotic FD was present in 56.9%, monostotic in 43.1%. MAS was diagnosed in 15.7%, with associated endocrinopathies: precocious puberty (4.9%), growth hormone excess (2.9%), cortisol excess (2.9%), and hypophosphatemia (5.9%). Café-au-lait macules were observed in 15.7%. Chronic bone pain was reported by 74.5% of patients, and fractures occurred in 38.2%, with 24.5% experiencing pathologic fractures attributable to FD. Osteoporosis was noted in 25.5%. ALP levels were significantly higher in MAS vs. non-MAS (275.5 vs. 95.7 U/L, p = 0.027). Vitamin D was significantly lower in monostotic vs. polyostotic FD (22.3 vs. 31.4 ng/mL, p = 0.041), although not associated with fracture risk. Differences in fracture rates by disease type, sex, MAS, or hypophosphatemia were not statistically significant. Bone-targeted therapy was used in 27.5%—primarily IV zoledronic acid or oral bisphosphonates—with reported pain improvement in 70% of IV-treated vs. 61.1% of oral-treated patients; this difference did not reach statistical significance. Only 41.1% of patients were evaluated by endocrinology despite documented endocrine comorbidities. Conclusion: Adults with FD/MAS experience a high burden of skeletal fragility, chronic pain, and metabolic complications. Biochemical differences by disease subtype—such as elevated ALP in MAS and lower vitamin D in monostotic FD—may reflect distinct underlying disease biology. Although no statistically significant predictors of fracture were identified, observed trends support the need for larger, prospective studies. The low rate of endocrine specialty follow-up—despite frequent hormonal involvement—underscores an opportunity to improve multidisciplinary care and long-term outcomes in this population. Presentation: Sunday, July 13, 2025

IntroductionDelirium is associated with an increased risk of post-hospitalization mortality. However, the impact of persistent delirium on mortality is not well defined.MethodsWe conducted a retrospective cohort study on the association of non-persistent or persistent delirium and mortality. We included patients aged > 65 years admitted to the Owensboro Health Regional Hospital between August 2021 and August 2022. Delirium was determined based on a score of ≥ 2 on the Nurse Delirium Screening Scale (NuDESC) recorded on all admitted patients three times a day during nursing shift change. Multivariate logistic regression models were used to evaluate the association between non-persistent or persistent delirium and 30-day, 60-day, 90-day, 180-day, and 360-day mortality after adjusting for covariates. Sensitivity analysis was performed to compare different definitions of delirium as ≥ 2, ≥ 3, or ≥ 4 days of delirium occurring consecutively or non-consecutively.Results4560 hospitalized patients were included in this study. Of these, 634 (13.9%) were identified as having delirium (persistent or non-persistent) and 3926 (86.1%) as without delirium. Patients with delirium were slightly older than those without (77 ± 7.9 vs. 79.5 ± 8.5 years old). The patients in each group were relatively comparable in terms of sex, race, smoking status, Medicare user status, and comorbidities. After adjusting for comorbidities, delirium was associated with an increase of mortality at 30 days for patients with persistent delirium of 2 days (aOR 4.88, 95% CI 3.63–6.54), 3 days (aOR 5.64, 95% CI 3.95–7.98), 4 days (aOR 7.21, 95% CI 4.74–10.8). Persistent delirium was associated with higher 60-day, 90-day, 180-day, and 360-day mortality rates, with an incremental increase in the risk of mortality for each additional day of delirium.ConclusionPersistent delirium is consistently associated with increased mortality, with an increased risk of mortality for each additional day of delirium, underscoring the need for early identification and treatment.

BackgroundThe shift to video care during the COVID-19 pandemic exacerbated disparities in health care access, especially among high-need, high-risk older adults with frailty.ObjectiveThe objective of this study was to quantify the ability of high-need, high-risk older veterans to use video visits for health care and identify factors associated with successful video visit completion.MethodsVeterans in a Veterans Affairs Frailty Intervention and Treatment (FIT) clinic underwent a physical, functional, psychological, social, and technology assessment at baseline. During the pandemic, the FIT clinic switched to televisits. We sorted patients into 4 groups: video visit, telephone visit, reached but no visit, and unable to contact. We performed a t test to compare normal variables and a chi-square test to compare categorical variables to identify factors associated with completing a video visit versus a telephone visit.ResultsWe attempted to contact 110 patients from the FIT clinic. They were 73.5 (SD 5.6) years old on average. A total of 46 (41.8%) patients were White, 46 (41.8%) patients were Black, and 17 (15.5%) patients were Hispanic. Sixty-seven (60.9%) patients had at least some college education, and 49 (44.5%) patients were very confident in filling out medical forms. Of the 110 patients, 72 patients were reached, and 65 patients agreed to a televisit. Of the 65 patients who agreed to a televisit, 19 (29.2%) patients completed a video visit, while 37 (57%) completed a telephone visit. A total of 19 patients out of 25 (76%) of those who scheduled a video visit completed it successfully. Compared with those who completed a telephone visit, veterans who completed a video visit were more likely to have access to a computer with a camera, microphone, and high-speed internet/data plan, as well as the ability to use email and be confident in internet use. They were more likely to have a higher health literacy score and be cognitively intact with a Montreal Cognitive Assessment score of ≥26, and were less likely to experience issues with walking, stepping, and balance.ConclusionsOur study found that completing a video visit requires access to technology, the ability to use it, and a willingness to do so. Among older veterans with frailty, only a quarter completed a video visit, and this group comprised patients who already had access to video-capable technology, used it, and were comfortable with it. They were also more often physically and cognitively intact compared with those who used telephone visits. Strategies to expand the use of video visits in the care of older adults include screening older adults to identify individuals most likely to succeed and increasing access to simple home telehealth technology.