Citations

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21 + cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21 + cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21 + cell clearance did not alter bone loss due to aging; conversely, p16 + cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21 + neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21 + OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell–like OCH subset that was p21 + and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21 + versus p16 + senescent/senescent-like cells that may be leveraged for therapeutic opportunities.

Introduction Subjectively experienced cognitive difficulties are common in youth with postural orthostatic tachycardia syndrome. The pathophysiological and psychological contributions of these cognitive impairments remain unclear. Method Participants were 96 adolescents and young adults diagnosed with postural orthostatic tachycardia syndrome and admitted to an intensive pain treatment program. Participants completed cognitive assessment and measures of postural orthostatic tachycardia syndrome symptoms, pain intensity, pain catastrophizing, anxiety, depression, and functional disability. Results Self-reported autonomic symptom intensity, but not severity of heart rate change, was associated with cognitive performance. Symptoms of depression were associated with decreases in most measures of cognitive functioning. Pain intensity, pain catastrophizing, and depression but not cognitive scores and physiological measures, were significant predictors of disability. Conclusion Depression appears to be a significant contributor to the cognitive difficulties in youth with postural orthostatic tachycardia syndrome. These findings highlight the importance of assessing and treating affective symptoms in this population along with medical and lifestyle approaches to treating postural orthostatic tachycardia syndrome symptoms.

Purpose: Population-based evidence in the interrelationships among hearing, brain structure, and cognition is limited. This study aims to investigate the cross-sectional associations of peripheral hearing, brain imaging measures, and cognitive function with speech-in-noise performance among older adults. Method: We studied 602 participants in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) brain magnetic resonance imaging (MRI) ancillary study, including 427 ACHIEVE baseline (2018–2020) participants with hearing loss and 175 Atherosclerosis Risk in Communities Neurocognitive Study Visit 6/7 (2016–2017/2018–2019) participants with normal hearing. Speech-in-noise performance, as outcome of interest, was assessed by the Quick Speech-in-Noise (QuickSIN) test (range: 0–30; higher = better). Predictors of interest included (a) peripheral hearing assessed by pure-tone audiometry; (b) brain imaging measures: structural MRI measures, white matter hyperintensities, and diffusion tensor imaging measures; and (c) cognitive performance assessed by a battery of 10 cognitive tests. All predictors were standardized to z scores. We estimated the differences in QuickSIN associated with every standard deviation ( SD ) worse in each predictor (peripheral hearing, brain imaging, and cognition) using multivariable-adjusted linear regression, adjusting for demographic variables, lifestyle, and disease factors (Model 1), and, additionally, for other predictors to assess independent associations (Model 2). Results: Participants were aged 70–84 years, 56% female, and 17% Black. Every SD worse in better-ear 4-frequency pure-tone average was associated with worse QuickSIN (−4.89, 95% confidence interval, CI [−5.57, −4.21]) when participants had peripheral hearing loss, independent of other predictors. Smaller temporal lobe volume was associated with worse QuickSIN, but the association was not independent of other predictors (−0.30, 95% CI [−0.86, 0.26]). Every SD worse in global cognitive performance was independently associated with worse QuickSIN (−0.90, 95% CI [−1.30, −0.50]). Conclusions: Peripheral hearing and cognitive performance are independently associated with speech-in-noise performance among dementia-free older adults. The ongoing ACHIEVE trial will elucidate the effect of a hearing intervention that includes amplification and auditory rehabilitation on speech-in-noise understanding in older adults. Supplemental Material: https://doi.org/10.23641/asha.25733679

AbstractBackgroundDespite the overall safety and efficacy of COVID‐19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post‐vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post‐vaccination.MethodsA cross‐sectional study was conducted among participants with self‐reported new‐onset SAIDs using the COVID‐19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset—a validated, patient‐reported e‐survey—to analyze the long‐term safety of COVID‐19 vaccines. Baseline characteristics of patients with new‐onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio.ResultsOf 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new‐onset SAID post‐vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new‐onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9–9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3–5.3; p = .004). New‐onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1–1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3–1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2–4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4–0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs.ConclusionThis study reports a low occurrence of new‐onset SAIDs following COVID‐19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre‐existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID‐19 vaccination in the general population. However, long‐term studies are needed to understand the autoimmune phenomena arising post‐vaccination.

This study aims to explore how artificial intelligence can help ease the burden on caregivers, filling a gap in current research and healthcare practices due to the growing challenge of an aging population and increased reliance on informal caregivers. We conducted a search with Google Scholar, PubMed, Scopus, IEEE Xplore, and Web of Science, focusing on AI and caregiving. Our inclusion criteria were studies where AI supports informal caregivers, excluding those solely for data collection. Adhering to PRISMA 2020 guidelines, we eliminated duplicates and screened for relevance. From 947 initially identified articles, 10 met our criteria, focusing on AI’s role in aiding informal caregivers. These studies, conducted between 2012 and 2023, were globally distributed, with 80% employing machine learning. Validation methods varied, with Hold-Out being the most frequent. Metrics across studies revealed accuracies ranging from 71.60% to 99.33%. Specific methods, like SCUT in conjunction with NNs and LibSVM, showcased accuracy between 93.42% and 95.36% as well as F-measures spanning 93.30% to 95.41%. AUC values indicated model performance variability, ranging from 0.50 to 0.85 in select models. Our review highlights AI’s role in aiding informal caregivers, showing promising results despite different approaches. AI tools provide smart, adaptive support, improving caregivers’ effectiveness and well-being.

Background: TAR DNA binding protein 43 (TDP-43) has been shown to be associated with whole hippocampal atrophy in primary age-related tauopathy (PART). It is currently unknown which subregions of the hippocampus are contributing to TDP-43 associated whole hippocampal atrophy in PART. Objective: To identify which specific hippocampal subfield regions are contributing to TDP-43-associated whole hippocampal atrophy in PART. Methods: A total of 115 autopsied cases from the Mayo Clinic Alzheimer Disease Research Center, Neurodegenerative Research Group, and the Mayo Clinic Study of Aging were analyzed. All cases underwent antemortem brain volumetric MRI, neuropathological assessment of the distribution of Aβ (Thal phase), and neurofibrillary tangle (Braak stage) to diagnose PART, as well as assessment of TDP-43 presence/absence in the amygdala, hippocampus and beyond. Hippocampal subfield segmentation was performed using FreeSurfer version 7.4.1. Statistical analyses using logistic regression were performed to assess for associations between TDP-43 and hippocampal subfield volumes, accounting for potential confounders. Results: TDP-43 positive patients ( n = 37, 32%), of which 15/15 were type-α, had significantly smaller whole hippocampal volumes, and smaller volumes of the body and tail of the hippocampus compared to TDP-43 negative patients. Subfield analyses revealed an association between TDP-43 and the molecular layer of hippocampal body and the body of cornu ammonis 1 (CA1), subiculum, and presubiculum regions. There was no association between TDP-43 stage and subfield volumes. Conclusions: Whole hippocampal volume loss linked to TDP-43 in PART is mainly due to volume loss occurring in the molecular layer, CA1, subiculum and presubiculum of the hippocampal body.

This cohort study examines the role of comprehensive bridging radiotherapy in the setting of chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.

Despite the growing presence of women and historically underrepresented groups in academic medicine, significant disparities remain. This article examines a key aspect of these disparities: biases in assessment and learning environments. Reviewing current literature, including in OBGYN, reveals persistent gender and racial biases in subjective clinical narrative assessments. The paper then outlines a 2-pronged approach for change: first, enhancing the learning environment, and subsequently, providing targeted recommendations for individuals, academic leaders, and healthcare institutions to effectively address these biases.

Background Self-scheduling of medical visits is becoming more common but the complexity of applying multiple requirements for self-scheduling has hampered implementation. Mayo Clinic implemented self-scheduling in 2019 and has been increasing its portfolio of self-schedulable visits since then. Our aim was to show measures quantifying the complexity associated with medical visit scheduling and to describe how opportunities and challenges of scheduling complexity apply in self-scheduling. Methods We examined scheduled visits from January 1, 2022, through August 24, 2023. For seven visit categories, we counted all unique visit types that were scheduled, for both staff-scheduled and self-scheduled. We examined counts of self-scheduled visit types to identify those with highest uptake during the study period. Results There were 9555 unique visit types associated with 20.8 M (million) completed visits. Self-scheduled visit types accounted for 4.0% (838,592/20,769,699) of the completed total visits. Of seven visit categories, self-scheduled established patient visits, testing visits, and procedure visits accounted for 93.5% (784,375/838,592) of all self-scheduled visits. Established patient visits in primary care (10 visit types) accounted for 273,007 (32.6%) of all self-scheduled visits. Testing visits (blood and urine testing, 2 visit types) accounted for 183,870 (21.9%) of all self-scheduled visits. Procedure visits for screening mammograms, bone mineral density, and immunizations (8 visit types) accounted for 147,358 (17.6%) of all self-scheduled visits. Conclusion Large numbers of unique visit types comprise a major challenge for self-scheduling. Some visit types are more suitable for self-scheduling. Guideline-based procedure visits such as screening mammograms, bone mineral density exams, and immunizations are examples of visits that have high volumes and can be standardized for self-scheduling. Established patient visits and laboratory testing visits also can be standardized for self-scheduling. Despite the successes, there remain thousands of specific visit types that may need some staff-scheduler intervention to properly schedule.