Citations

Abstract Introduction The majority of adults with inflammatory bowel disease (IBD) experience disability which is not fully explained by disease activity. Up to 80% of adults with IBD experience poor sleep health, which is associated with disability in other populations; however, the relationship between disability and sleep health among patients with IBD is largely unexamined. The purpose of this study was to compare the sleep health characteristics of those with and without IBD-related disability. Methods We recruited adults (18 to 59 years old) with IBD from a single academic medical center from 2022 to 2024. We measured disease activity using the Manitoba IBD Index and sleep using the PROMIS Sleep Disturbance and PROMIS Sleep-Related Impairment scales, the Insomnia Severity Index, and 14 days of wrist-worn actigraphy (Phillips Spectrum Plus, Phillips Respironics). We asked participants how many days they missed or had at least 50% reduced productivity in paid work or household work or missed leisure activities in the last 3 months related to their IBD. Disability was defined as missing six or more day over three months. We conducted bivariate analyses and logistic regressions to study associations. Results Among 83 adults with IBD [mean age = 40.4 years (SD 10.7), 59 (71.1%) were female, 56 (71.1%) had Crohn’s disease], and 49 (62.0%) had IBD-related disability. Patients with disability had more severe sleep disturbance (56.4 vs. 51.0, p <.001), sleep-related impairment (58.3 vs 50.3, p <.001), more severe insomnia (12.7 vs. 9.4, p =.029), and actigraph-measured higher wake after sleep onset (41.6 minutes vs. 34.0 minutes, p = 0.012) and lower sleep efficiency (85.1% vs. 87.9%, p = 0.032) compared to those without disability. After controlling for age and disease activity, sleep-related impairment (OR = 1.1, 95% CI 1.03, 1.15) was independently associated with disability. Conclusion Patients with IBD-related disability experience poor sleep health. Sleep related daytime impairment uniquely contributed to disability when controlling for disease activity. Sleep interventions need to be tested in adults with IBD to determine if they are effective at addressing disability in this population. Support (if any) Mayo Clinic Bonner Fund

Abstract Introduction Sleep apnea impacts 50-70% of patients following stroke. Treatment of obstructive sleep apnea (OSA) in patients with stroke using continuous positive airway pressure (CPAP) has been recommended in recent American Heart Association/American Stroke Association guidelines. However, stroke patients poorly tolerate CPAP and often remain untreated. There is a paucity of data regarding alternative treatments such as oral appliance therapy (OAT) in stroke patients. We hypothesized that oral appliance therapy would be an efficacious option in the treatment of OSA in stroke patients, defined as a ≥50% reduction in apnea-hypopnea index (AHI) or oxygen desaturation index (ODI) or reduction in total AHI or ODI to < 10/h. Methods We performed a retrospective review of patients with OSA treated with OAT at our institution and had a history of stroke prior to receiving the oral appliance. Chart abstraction included demographic data, stroke type, sleep apnea diagnostic data, and efficacy data. Efficacy data included repeat sleep studies, overnight oximetry, patient reported outcomes, and subjective benefit, as available. Results 23 patients (52% female, mean age 63) were identified with a history of stroke prior to use of OAT for OSA. Baseline parameters (mean, SD) included BMI (30.8, 4.2), AHI (15.0, 10.6), and Epworth Sleepiness Scale (ESS) (9.3, 5.4). Post-treatment parameters included (mean, SD) BMI (30.1, 4.2), AHI (12.4, 12.0), and ESS (6.5, 4.0). 12 patients had both baseline and follow-up sleep studies performed which met criteria for AHI efficacy of OAT in 7 of 12 (58%). Wilcoxon signed rank exact test demonstrated improvement in median AHI of 9.3 (0.40-17.6, p< 0.05) among these 12 patients. 2 of 3 (67%) patients with overnight oximetry follow-up met criteria for ODI efficacy of OAT. Of 8 patients with only subjective follow-up, 6 (75%) reported subjective improvement and 2 (25%) did not tolerate the device. Conclusion This study demonstrated that oral appliance therapy is efficacious in reducing the AHI by at least 50% or to a value below 10 in a majority of patients. Oral appliance therapy may be a viable alternative to CPAP in selected OSA patients with a history of stroke. Support (if any) No support

Abstract Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is the single strongest predictor of Parkinson’s disease (PD) risk. Given neurotrauma and psychiatric morbidity, the aging post-9/11 Veteran cohort is a target population for understanding probable RBD frequency and neuroprotection opportunities. We previously reported over 50% of post-9/11 Veterans screened positive for probable RBD. We aimed to examine frequencies of prodromal PD markers and polysomnography (PSG)-confirmed RBD in post-9/11 Veterans. Methods Veterans with probable RBD based on the single-question RBD screen (n=12) were recruited from the Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS) Houston cohort. Participants were assessed for subthreshold parkinsonism (Unified Parkinson’s Disease Rating Scale-III Motor score >3, excluding action tremor), olfactory loss (12-item Sniffin’ Sticks), TBI exposures, autonomic symptoms, orthostasis, excessive daytime sleepiness, post-traumatic stress disorder (PTSD), and psychiatric comorbidities. PSG studies were conducted per American Academy of Sleep Medicine guidelines. A board-certified sleep physician confirmed the presence of REM sleep without atonia. We compared the frequency of prodromal marker positivity between participants with and without subthreshold parkinsonism. Results All 12 participants were male (6 [50%] Black, 3 [25%] Hispanic) with a mean (SD) age of 44.4 ± 6.7 years. PSG data (n=10) revealed REM sleep without atonia in 5 (50%), moderate obstructive sleep apnea (OSA) in 2 (20%), and severe OSA in 2 (20%) participants. Five (41.6%) participants had mild motor dysfunction suggestive of subthreshold parkinsonism on the UPDRS-III (M±SD score of 8.6 ± 5.9), while 7 participants had normal or low UPDRS-III ratings (2.3 ± 1.3; p=0.02). Veterans with subthreshold parkinsonism had lower Sniffin’ Sticks scores than those without (M±SD 9.4 ± 2.07 vs. 11.29 ± 0.76; 95% CI: 0.01–3.76, p=0.049). Conclusion This pilot study suggests that motor and olfactory prodromal PD markers are frequent in post-9/11 Veterans with probable RBD. Larger prospective cohort studies are required to further quantify REM sleep without atonia and assess synuclein-specific biomarkers in this population. Support (if any) Center for Alzheimer’s and Neurodegenerative Diseases at Baylor College of Medicine [MJ]; VA CSR&D (#IK2CX002363-01A1) [MJ]; VA RR&D (B9268-X) [RJ]; NIH/NIA/NINDS (U19-AG071754 & R34-AG056639) [ES]; and AASM [ES].

ABSTRACT Aim To describe interventions to mitigate weight bias among practicing healthcare providers and examine their effectiveness. Design An integrative review. Methods The framework of Whittemore and Knafl (2005) was utilised to identify and synthesise studies of weight bias interventions. Covidence reference management software facilitated screening using predetermined eligibility criteria that is, published in peer‐reviewed journals, reported in English, and described outcomes for weight bias mitigation interventions among healthcare providers with a professional practice licence. We evaluated study quality using Joanna Briggs Institute's Critical Appraisal Tools for qualitative and quantitative studies. Data Sources Five databases were searched (CINAHL, Embase, EBSCOhost, APA PsycINFO, and Scopus) in July 2024. Results Sixteen articles met the inclusion criteria. Four themes emerged: (1) active learning lessens weight bias more than passive learning, (2) multicomponent approaches yield better outcomes, (3) healthcare providers are willing to change their practices, and (4) explicit attitudes and beliefs are more amenable to change than implicit ones. Four sub‐themes within theme one included the use of in‐person workgroups; films, computer‐based, and podcast delivery; written modules; and physical characteristic modifications, such as the use of an adiposity empathy suit. Intervention designs using a theory‐based, active learning approach with repeated sessions were most successful at decreasing negative weight‐biased attitudes and beliefs. Conclusions Interventions that effectively reduce weight bias among practicing healthcare providers vary, yet evidence suggests that weight bias mitigation is achievable. These interventions offer strategies to improve patient‐centred care among patients living with obesity. Impact Healthcare providers often display weight bias. This review synthesises information on effective interventions for reducing bias, which may limit the subsequent negative patient outcomes associated with it. Reporting Method The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses was the structure used for this paper. Patient or Public Contribution There were no patient or public contributions.

Background/Objectives: Staphylococci are the most common causes of periprosthetic joint infection (PJI); new antimicrobials are needed to manage these difficult infections. Nisin A is a lantibiotic peptide derived from Lactococcus lactis that has antimicrobial activity against Gram-positive bacteria, including staphylococci, and is an FDA-approved preservative used in the food and dairy industry. Here, the in vitro nisin A susceptibility of PJI-associated staphylococci was assessed. Methods: The minimum inhibitory concentrations (MICs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm bactericidal concentrations (MBBCs) of nisin A were measured by broth microdilution against 106 staphylococcus isolates isolated from PJI. MICs were assessed using 5 × 105 CFU/mL plus nisin A. For MBICs, biofilms were grown on pegged lids for 6 h, followed by 20 h of treatment. For MBBCs, pegged lids were transferred to plates containing media only for 20 h. The results were determined as the lowest concentrations with no visual growth. Two-dimensional MICs with nisin A and vancomycin were assessed for 20 isolates. Fractional inhibitory concentrations (FICs) were calculated to determine synergistic, additive, antagonistic, or indifferent interactions. Results: The MIC that inhibited 90% of S. aureus and S. epidermidis was 4 µg/mL, apart from for the MRSA subset (8 µg/mL). The MBIC that inhibited 90% of isolates was 4 µg/mL. The MBBCs ranged from 4 to 256 µg/mL. When tested together, nisin A and vancomycin yielded an FIC between 1.25 and 1.5, indicative of indifference, except for one isolate each of MRSA and MSSA, for which an additive effect (FIC of 1) was observed. Conclusions: Nisin A showed inhibitory activity against staphylococci that cause PJI.

ABSTRACT Evidence indicates that the integrity of in utero development influences late life healthy or unhealthy aging; however, specific links between them are unclear. Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage‐specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of Hira in tyrosinase+ neural crest‐derived lineages, including melanoblasts, led to reduced melanoblast numbers during embryogenesis, with single‐cell RNA sequencing analysis indicating evidence of lineage‐specificity defects. This was supported in an in vitro model using melb‐a melanoblasts in which Hira knockdown affected lineage identity and melanoblast differentiation potential, with ATAC‐seq data indicating a role of HIRA in orchestrating chromatin accessibility. Interestingly, however, newborn Hira knockout mice had wild type numbers of differentiated melanocytes, albeit functionally defective, as demonstrated by very mild hypopigmentation of the first hair coat, increased melanocyte telomere‐associated DNA damage foci, and impaired response to proliferative challenge. Moreover, as they aged, mice with embryonic melanoblast Hira knockout displayed marked defects in melanocyte stem cell maintenance and premature hair graying. Importantly, this phenotype was not observed after postnatal inducible knockout, indicating an essential role for HIRA at embryonic stages that is transmitted to adulthood, rather than a direct postnatal requirement within the pigmentary system. This genetic model shows that HIRA function during early development lays a foundation for maintaining lineage identity and subsequent maintenance of adult tissue‐specific stem cells during aging.

Abstract RATIONALE: Airway-to-lung ratio (AirLR), calculated as the mean of airway lumen diameters at standard anatomic locations divided by the cube-root of total lung volume, is associated with COPD risk regardless of smoking status, and we have previously shown an association between total-pulmonary-vascular-volume-to-lung-size relationship with AirLR. [PMCID: PMC11284327] Using dual energy computed tomography (DECT), we recently developed a deep learning-based algorithm for pulmonary arterial segmentation to compute pulmonary-arterial-to-lung ratio (ArtLR) which correlated significantly with AirLR and markers COPD. Here we automate image processing in a larger cohort to estimate ArtLR, introduce an alternative ArtLR standardization and correlate it to COPD-related measures of lung structure and function. METHODS: Using a SPIROMICS sub-cohort (110 participants), imaged via contrast enhanced DECT at functional residual capacity (FRC), an automatic deep learning pipeline segmented the arteries from the pulmonary vascular tree. Another pipeline automatically extracted the centerlines and calculated average arterial segment diameters. A paired non-contrast total lung capacity (TLC) scan was registered to the DECT FRC scan to transfer airway segment labels from the TLC to FRC domain. AirLR was calculated as the mean of airway lumen diameters at standard anatomic locations (trachea-to-subsegments) divided by cube root of lung volume [TLC or FRC]. A simple Long Short-Term Memory (LSTM) network was used to find corresponding anatomic arterial segments. Associations between ArtLR and %Emphysema, AirLR, pre- and post-bronchodilator FEV1/FVC, and a texture-based (AMFM) measure of %broncho-vascular bundles was assessed using linear regression to adjust for age, sex and BMI. RESULTS: In adjusted analyses, a 1-SD decrement in ArtLR-TLC was associated with 4.198 units increase in %Emphysema-910 (95%CI: 1.360-7.037; p = 0.0041), and 0.8198 units decrease in %Bronchovascular (95%CI: 0.5037-1.136; p < 0.0001). A 1-SD increment in ArtLR-TLC was associated with 0.2515 SD increase in AirLR-Outer (95%CI: 0.04947SD-0.4536SD; p = 0.0152), and 0.02083 units increase in PreBronch-FEV1FVC (95%CI: 0.001814-0.03984; p = 0.0321). Sex and BMI show significant associations with ArtLR-TLC, where female is associated with 1.068 SD decrease in ArtLR, and a unit increase in BMI is associated with 0.05788 SD increase in ArtLR (both p-values < 0.0001), and age was not association with ArtLR. CONCLUSIONS: An automated pipeline for pulmonary arterial tree segmentation and standardization from contrast enhanced DECT FRC scans demonstrates a significant relationship between ArtLR and AirLR as well as between ArtLR and %emphysema, and FEV1/FVC. A standardized method of arterial tree size assessment provides for expanded exploration of vascular vs airway disease etiologies.

Objective To develop and validate classification criteria for pediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by EULAR and the American College of Rheumatology (ACR). Methods This international initiative had 4 phases: (1) candidate items were proposed in a survey of pediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. Results The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anemia, C‐reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. Conclusion These new classification criteria for pediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.