Hospital readmissions among adults living with and without HIV in the US: findings from the Nationwide Readmissions Database.

Background: Thirty-day hospital readmission measures quality of care, but there are limited data among people with HIV (PWH) and people without HIV (PWoH) in the era of universal recommendation for antiretroviral therapy. We descriptively compared 30-day all-cause, unplanned readmission risk between PWH and PWoH. Methods: A retrospective cohort study was conducted using the 2019 Nationwide Readmissions Database (2019/01/01-2019/12/31), an all-payer database that represents all US hospitalizations. Index (initial) admissions and readmissions were determined using US Centers for Medicare & Medicaid Services definitions. Crude and age-adjusted risk ratios (aRR) comparing the 30-day all-cause, unplanned readmission risk between PWH to PWoH were estimated using random effect logistic regressions and predicted marginal estimates. Survey weights were applied to all analyses. Findings: We included 24,338,782 index admissions from 18,240,176 individuals. The median age was 52(IQR = 40-60) years for PWH and 61(IQR = 38-74) years for PWoH. The readmission risk was 20.9% for PWH and 12.2% for PWoH (age-adjusted-RR:1.88 [95%CI = 1.84-1.92]). Stratified by age and sex, young female (age 18-29 and 30-39 years) PWH had a higher readmission risk than young female PWoH (aRR = 3.50 [95%CI = 3.11-3.88] and aRR = 4.00 [95%CI = 3.67-4.32], respectively). While the readmission risk increased with age among PWoH, the readmission risk was persistently high across all age groups among PWH. The readmission risk exceeded 30% for PWH admitted for hypertensive heart disease, heart failure, and chronic kidney disease. Interpretation: PWH have a disproportionately higher risk of readmission than PWoH, which is concerning given the aging profile of PWH. More efforts are needed to address readmissions among PWH. Funding: US National Institutes of Health.

Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.

This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose. Pharmacokinetic parameters of soticlestat and its metabolites TAK-935-G (M3) and M-I were assessed and compared by group. The incidence of treatment-emergent adverse events (TEAEs) and other safety parameters were also monitored. The pharmacokinetic analyses comprised 35 participants. Participants with moderate hepatic impairment had lower proportions of bound and higher proportions of unbound soticlestat than participants with mild hepatic impairment and normal hepatic function. Total plasma soticlestat pharmacokinetic parameters (maximum observed concentration [Cmax], area under the concentration-time curve from time 0 to time of last quantifiable concentration [AUClast], and AUC from time 0 to infinity [AUC∞]) were approximately 115%, 216%, and 199% higher with moderate and approximately 45%, 35%, and 30% higher with mild hepatic impairment, respectively, than healthy matched participants. Moderate hepatic impairment decreased the liver's ability to metabolize soticlestat to M-I; glucuronidation to M3 was also affected. Mild hepatic impairment resulted in a lower total plasma M-I exposure, but glucuronidation was unaffected. TEAEs were similar across study arms, mild, and no new safety findings were observed. A soticlestat dose reduction is required for individuals with moderate but not mild hepatic impairment.

OpenHands: An Open-Source Statistical Shape Model of the Finger Bones.

This paper presents statistical shape models of the four fingers of the hand, with an emphasis on anatomic analysis of the proximal and distal interphalangeal joints. A multi-body statistical shape modelling pipeline was implemented on an exemplar training dataset of computed tomography (CT) scans of 10 right hands (5F:5M, 27-37 years, free from disease or injury) imaged at 0.3 mm resolution, segmented, meshed and aligned. Model generated included pose neutralisation to remove joint angle variation during imaging. Repositioning was successful; no joint flexion variation was observed in the resulting model. The first principal component (PC) of morphological variation represented phalanx size in all fingers. Subsequent PCs showed variation in position along the palmar-dorsal axis, and bone breadth: length ratio. Finally, the models were interrogated to provide gross measures of bone lengths and joint spaces. These models have been published for open use to support wider community efforts in hand biomechanical analysis, providing bony anatomy descriptions whilst preserving the security of the underlying imaging data and privacy of the participants. The model describes a small, homogeneous population, and assumptions cannot be made about how it represents individuals outside the training dataset. However, it supplements anthropometric datasets with additional shape information, and may be useful for investigating factors such as joint morphology and design of hand-interfacing devices and products. The model has been shared as an open-source repository ( https://github.com/abel-research/OpenHands ), and we encourage the community to use and contribute to it.

The cortical amygdala consolidates a socially transmitted long-term memory.

Social communication guides decision-making, which is essential for survival. Social transmission of food preference (STFP) is an ecologically relevant memory paradigm in which an animal learns a desirable food odour from another animal in a social context, creating a long-term memory1,2. How food-preference memory is acquired, consolidated and stored is unclear. Here we show that the posteromedial nucleus of the cortical amygdala (COApm) serves as a computational centre in long-term STFP memory consolidation by integrating social and sensory olfactory inputs. Blocking synaptic signalling by the COApm-based circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage or recall. COApm-mediated STFP memory consolidation depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus. STFP memory consolidation requires protein synthesis, suggesting a gene-expression mechanism. Deep single-cell and spatially resolved transcriptomics revealed robust but distinct gene-expression signatures induced by STFP memory formation in the COApm that are consistent with synapse restructuring. Our data thus define a neural circuit for the consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein-synthesis-dependent memory consolidation from memory acquisition, storage or retrieval.

A Rheological Study on the Effect of Tethering Pro- and Anti-Inflammatory Cytokines into Hydrogels on Human Mesenchymal Stem Cell Migration, Degradation, and Morphology.

Polymer-peptide hydrogels are being designed as implantable materials that deliver human mesenchymal stem cells (hMSCs) to treat wounds. Most wounds can progress through the healing process without intervention. During the normal healing process, cytokines are released from the wound to create a concentration gradient, which causes directed cell migration from the native niche to the wound site. Our work takes inspiration from this process and uniformly tethers cytokines into the scaffold to measure changes in cell-mediated degradation and motility. This is the first step in designing cytokine concentration gradients into the material to direct cell migration. We measure changes in rheological properties, encapsulated cell-mediated pericellular degradation and migration in a hydrogel scaffold with covalently tethered cytokines, either tumor necrosis factor-α (TNF-α) or transforming growth factor-ß (TGF-ß). TNF-α is expressed in early stages of wound healing causing an inflammatory response. TGF-ß is released in later stages of wound healing causing an anti-inflammatory response in the surrounding tissue. Both cytokines cause directed cell migration. We measure no statistically significant difference in modulus or the critical relaxation exponent when tethering either cytokine in the polymeric network without encapsulated hMSCs. This indicates that the scaffold structure and rheology is unchanged by the addition of tethered cytokines. Increases in hMSC motility, morphology and cell-mediated degradation are measured using a combination of multiple particle tracking microrheology (MPT) and live-cell imaging in hydrogels with tethered cytokines. We measure that tethering TNF-α into the hydrogel increases cellular remodeling on earlier days postencapsulation and tethering TGF-ß into the scaffold increases cellular remodeling on later days. We measure tethering either TGF-ß or TNF-α enhances cell stretching and, subsequently, migration. This work provides rheological characterization that can be used to design new materials that present chemical cues in the pericellular region to direct cell migration.

HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy.

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.

An exploratory study on lipidomic profiles in a cohort of individuals with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 adults with PTSD and 40 trauma-exposed non-PTSD individuals (n = 20/sex/condition; 19-39 years old). Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, ~ 90 measures were collected, on sleep, and mental and physical health indices. Poorer sleep quality was associated with greater PTSD severity in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 lipid subclasses. After adjusting for BMI and sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The correlations between triglycerides and ceramide metabolites with cholesterol metabolites and systolic blood pressure were dependent upon sex and PTSD status. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher body mass may have contributed to changes in the lipidome found in PTSD.

Randomized Controlled Trial of 60 minutes for Health With Rapid Antiretroviral Therapy to Reengage Persons With HIV Who Are Out of Care.

BACKGROUND: Many persons with HIV remain out of care (PWH-OOC). We evaluated InstaCare, a complex intervention integrating the brief behavioral intervention 60 minutes for Health with the rapid restart of antiretroviral therapy (rapid ART). SETTING: Prospective open-label randomized controlled trial among PWH-OOC in San Diego, USA. METHODS: PWH-OOC were randomized 1:1 to InstaCare or a time-and-attention control integrating a diet-and-nutrition behavioral intervention also with rapid ART initiation (restart ≤7 days from enrollment). All participants had access to support services (free transport, HIV peer navigation, adherence counseling, and linkage to care) and primary care services (mental health, case management, social work, medication-assisted treatment, and specialist pharmacy). The primary outcomes were viral suppression (<50 copies/mL) and re-engagement with care (≥2 HIV care visits >90 days apart) by 24 weeks. Outcomes were reported on an intention-to-treat basis. RESULTS: Between November 2020 and August 2022, 52 PWH-OOC were enrolled. Baseline substance use in the preceding month (49%), unstable housing (51%), moderate/severe depression (49%), and moderate/severe anxiety (41.7%) were prevalent. Rapid ART was provided for all participants. At week 24, the proportion with HIV viral load <50 copies/mL was 37.3% (19/51) (InstaCare 28.0%, control 46.2%, P = 0.25). Fourteen (27.5%) were engaged with care (InstaCare 7/25 [28.0%], control 7/26 [26.9%], P = 1.00). Most participants (94%) reported low or very low emotional distress associated with rapid ART. Study lost to follow-up by week 24 was high (23/51, 45%). CONCLUSIONS: The InstaCare complex intervention did not improve viral suppression or reengagement with care among PWH-OOC. Investigation of high-intensity, individually adapted interventions is needed among PWH-OOC.

SurvNet: A low-complexity convolutional neural network for survival time classification of patients with glioblastoma.

Background and objective: Malignant primary brain tumors cause the greatest number of years of life lost than any other cancer. Grade 4 glioma is particularly devastating: The median survival without any treatment is less than six months and with standard-of-care treatment is only 14.6 months. Accurate identification of the overall survival time of patients with brain tumors is of profound importance in many clinical applications. Automated image analytics with magnetic resonance imaging (MRI) can provide insights into the prognosis of patients with brain tumors. Methods: In this paper, We propose SurvNet, a low-complexity deep learning architecture based on the convolutional neural network to classify the overall survival time of patients with brain tumors into long-time and short-time survival cohorts. Through the incorporation of diverse MRI modalities as inputs, we facilitate deep feature extraction at various anatomical sites, thereby augmenting the precision of predictive modeling. We compare SurvNet with the Inception V3, VGG 16 and ensemble CNN models on pre-operative magnetic resonance image datasets. We also analyzed the effect of segmented brain tumors and training data on the system performance. Results: Several measures, such as accuracy, precision, and recall, are calculated to examine the perfor-mance of SurvNet on three-fold cross-validation. SurvNet with T1 MRI modality achieved a 62.7 % accuracy, compared with 52.9 % accuracy of the Inception V3 model, 58.5 % accuracy of the VGG 16 model, and 54.9 % of the ensemble CNN model. By increasing the MRI input modalities, SurvNet becomes more accurate and achieves 76.5 % accuracy with four MRI modalities. Combining the segmented data, SurvNet achieved the highest accuracy of 82.4 %. Conclusions: The research results show that SurvNet achieves higher metrics such as accuracy and f1-score than the comparisons. Our research also proves that by using multiparametric MRI modalities, SurvNet is able to learn more image features and performs a better classification accuracy. We can conclude that SurvNet with the complete scenario, i.e., segmented data and four MRI modalities, achieved the best accuracy, showing the validity of segmentation information during the survival time prediction process.

Knee Angle Estimation from Surface EMG during Walking Using Attention-Based Deep Recurrent Neural Networks: Feasibility and Initial Demonstration in Cerebral Palsy.

Accurately estimating knee joint angle during walking from surface electromyography (sEMG) signals can enable more natural control of wearable robotics like exoskeletons. However, challenges exist due to variability across individuals and sessions. This study evaluates an attention-based deep recurrent neural network combining gated recurrent units (GRUs) and an attention mechanism (AM) for knee angle estimation. Three experiments were conducted. First, the GRU-AM model was tested on four healthy adolescents, demonstrating improved estimation compared to GRU alone. A sensitivity analysis revealed that the key contributing muscles were the knee flexor and extensors, highlighting the ability of the AM to focus on the most salient inputs. Second, transfer learning was shown by pretraining the model on an open source dataset before additional training and testing on the four adolescents. Third, the model was progressively adapted over three sessions for one child with cerebral palsy (CP). The GRU-AM model demonstrated robust knee angle estimation across participants with healthy participants (mean RMSE 7 degrees) and participants with CP (RMSE 37 degrees). Further, estimation accuracy improved by 14 degrees on average across successive sessions of walking in the child with CP. These results demonstrate the feasibility of using attention-based deep networks for joint angle estimation in adolescents and clinical populations and support their further development for deployment in wearable robotics.

Anterior cervical hybrid constructs reduce superior adjacent segment burden compared to multilevel anterior cervical discectomy and fusion.

Background: Traditional surgical treatment for symptomatic cervical degenerative disc disease is anterior cervical discectomy and fusion (ACDF), yet the increased risk of adjacent segment degeneration (ASD) requiring additional surgery exists and may result in limiting long-term surgical success when it occurs. Disc arthroplasty can preserve or restore physiologic range of motion (ROM), decreasing adjacent level stress and subsequent surgery. For patients with multilevel pathology requiring at least a 1-level fusion, interest is growing in anterior cervical hybrid (ACH) surgery as a partial motion-preserving procedure to decrease the adjacent level burden. This radiographic study compares postoperative superior adjacent segment motion between ACH and ACDF. Secondarily, total global motion, construct motion, inferior adjacent segment motion, and sagittal alignment parameters were compared. Methods: This is a single-center, multi-surgeon, retrospective cohort study of 2- and 3-level ACH and ACDF cases between 2013 and 2021. Degrees of motion were analyzed on flexion/extension views using Cobb angles to measure global (C2-C7) construct and adjacent segment lordosis. Neutral lateral X-rays were analyzed for alignment parameters, including global lordosis, cervical sagittal vertical axis (cSVA), and T1 slope (T1S). Differences were determined by independent t-test and Fisher's exact test. Results: Of 100 patients, 38% were 2-level cases (47% ACH, 53% ACDF) and 62% were 3-level cases: (52% ACH, 48% ACDF). Postoperatively, superior adjacent segment motion increased with ACDF and decreased with ACH (-1.3°±5.3° ACH, 1.6°±4.6° ACDF, P=0.005). Postoperatively, the ACH group had greater ROM across the construct (16.3°±8.7° ACH, 4.7°±3.3° ACDF, P<0.001) and total global ROM (38.0°±12.8° ACH, 28.0°±11.1° ACDF, P<0.001). ACH resulted in a significant reduction of motion loss across the construct (-10.0°±11.7° ACH, -18.1°±10.8° ACDF, P<0.001). Postoperative alignment restoration was similar between both cohorts (-2.61°±8.36° ACH, 0.04°±12.24° ACDF, P=0.21). Conclusions: Compared to ACDF, hybrid constructs partially preserved motion across operative levels and had greater postoperative global ROM without increasing superior adjacent segment mobility or sacrificing alignment restoration. This supports the consideration of ACH in patients with multilevel degenerative cervical pathology requiring at least a 1-level fusion and suggests a propensity for long-term success by reducing the superior adjacent segment burden.

Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.

To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits.

Wax "Tails" Enable Planthopper Nymphs to Self-Right Midair and Land on Their Feet.

The striking appearance of wax 'tails' - posterior wax projections on planthopper nymphs - has captivated entomologists and naturalists alike. Despite their intriguing presence, the functional roles of these formations remain largely unexplored. This study leverages high-speed imaging to uncover the biomechanical implications of wax structures in the aerial dynamics of planthopper nymphs (Ricania sp.). We quantitatively demonstrate that removing wax tails significantly increases body rotations during jumps. Specifically, nymphs without wax undergo continuous rotations, averaging 4.2 ± 1.8 per jump, in contrast to wax-intact nymphs, who do not complete a full rotation, averaging only 0.7 ± 0.2 per jump. This along with significant reductions in angular and translational velocity from takeoff to landing suggest that aerodynamic drag forces on wax structures effectively counteract rotation. These stark differences in body rotation correlate with landing success: nymphs with wax intact achieve a near perfect landing rate of 98.5%, while those without wax manage only a 35.5% success rate. Jump trajectory analysis reveals that wax-intact jumps transition from parabolic to asymmetric shapes at higher take-off velocities and show a significantly greater reduction in velocity from takeoff to landing compared to wax-removed jumps, demonstrating how wax structures help nymphs achieve more stable, controlled descents. Our findings confirm the aerodynamic self-righting functionality of wax tails in stabilizing planthopper nymph landings, advancing our understanding of the complex relationship between wax morphology and aerial maneuverability, with broader implications for wingless insect aerial adaptations and bioinspired robotics.

LazyAF, a pipeline for accessible medium-scale in silico prediction of protein-protein interactions.

Artificial intelligence has revolutionized the field of protein structure prediction. However, with more powerful and complex software being developed, it is accessibility and ease of use rather than capability that is quickly becoming a limiting factor to end users. LazyAF is a Google Colaboratory-based pipeline which integrates the existing ColabFold BATCH software to streamline the process of medium-scale protein-protein interaction prediction. LazyAF was used to predict the interactome of the 76 proteins encoded on the broad-host-range multi-drug resistance plasmid RK2, demonstrating the ease and accessibility the pipeline provides.

Therapeutic effect of NEO400, perillyl alcohol conjugated to linoleic acid, in a mouse model of UV-induced skin damage.

Excessive exposure to ultraviolet radiation (UVR) causes harmful effects on human skin. Pre-exposure application of sunscreen can be protective, but not after damage already has occurred. There is a need for agents that can be applied post-UVR exposure to repair the damage. We investigated a novel compound, NEO400, that appears to meet this medicinal need. NEO400 was created by conjugating linoleic acid to perillyl alcohol. UVR was repeatedly administered to the skin of mice over several weeks, where it caused the typical signs of UV damage, including scaling of the skin, DNA damage, and elevated levels of inflammatory cytokines. However, when NEO400 was applied immediately post-UVR, it triggered the appearance of markers for dermal stem cell proliferation, and no signs of skin damage emerged. Furthermore, when NEO400 was applied to skin that already had incurred significant damage, it accelerated skin healing. When applied individually, linoleic acid and perillyl alcohol were ineffective, indicating that they had to be conjugated in order to exert therapeutic efficacy. None of these skin-protective effects could be achieved with Aloe vera gel, a popular and widely used post-exposure remedy. Our study suggests that NEO400 holds potential as a regenerative treatment for excessively UVR-exposed skin.

Optimizing Triage of Ambulatory Patients With Advanced Heart Failure: 2-Year Outcomes From REVIVAL.

BACKGROUND: Left ventricular assist device (LVAD) use remains uncommon in advanced heart failure (HF) patients not dependent on inotropes. OBJECTIVES: Before considering a randomized trial comparing a strategy of earlier use of LVAD to continued medical therapy, a better understanding is needed of the clinical trajectory of ambulatory patients with advanced systolic HF on optimal guideline-directed medical therapy (GDMT). METHODS: REVIVAL enrolled 400 patients with advanced ambulatory systolic HF, ≥1 HF mortality risk marker (≥2 HF hospitalizations past year; or HF hospitalization and high natriuretic peptide; or no HF hospitalizations but low peak oxygen consumption, 6-minute walk, serum sodium, HF survival score or Seattle HF model predicted survival), and no LVAD contraindication at 21 LVAD centers from July 2015 to June 2016. Patients were followed for 2 years or until a primary outcome (death, durable ventricular assist device, or urgent transplant). Clinical outcomes and health-related quality of life were evaluated. RESULTS: Mean baseline left ventricular ejection fraction was 21%, median 6-minute walk was 341 m, and 92% were Interagency Registry for Mechanically Assisted Circulatory Support profiles 5 to 7. Adherence to GDMT and electrical device therapies was robust. Composite primary outcome occurred in 22% and 37% at 1 and 2 years, with death alone in 8% and 16%, respectively. Patients surviving for 2 years maintained GDMT intensity and had no decline in health-related quality of life. CONCLUSION: Structured, serial follow-up at programs with expertise in caring for advanced ambulatory systolic HF patients facilitates triage for advanced therapies. Better strategies are still needed to avoid deaths in a small but significant group of patients who die without advanced therapies. REVIVAL patients not selected for VAD or transplant have robust survival and patient-reported outcomes, which challenges advocacy for earlier VAD implantation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).

Surviving extreme radiation.

Tiny animals known as tardigrades use a combination of DNA repair machinery and a novel protein to mend their genome after intense ionizing radiation.

Lifetime trauma exposure and arthritis in older adults.

OBJECTIVE: Experiencing potentially traumatic events across one's lifecourse increases risk for poor physical health outcomes. Existing models emphasize the effects of any lifetime trauma exposure, risk accumulation (multiple traumas over time), and sensitive periods of exposure (specific exposure timepoints leading to lasting consequences). We examined how different indices of trauma exposure across the lifecourse were associated with later life arthritis, a common and debilitating health condition. METHODS: Data include 5,717 Health and Retirement Study participants (age mean = 65.3, SD = 12.9) who reported on lifetime adversity and trauma in 2006-2008. Lifetime trauma exposure was modeled as any trauma, accumulation of traumas, and lifecourse profiles (no exposure, childhood only, adulthood only, childhood and adulthood exposure). Outcomes included prevalent arthritis at baseline and incident arthritis across 12 years of follow-up. Covariate-adjusted generalized linear models for prevalence ratios (PR) and Cox proportional hazards models for hazard ratios (HR) were conducted. RESULTS: Any lifetime trauma was associated with both prevalent arthritis at baseline (PR = 1.13, 95%CI 1.05-1.22) and incident arthritis over 12 years (HR = 1.25, 95%CI 1.17-1.47). Greater trauma accumulation was significantly associated with both prevalent and incident arthritis. Childhood exposure was particularly strongly associated with prevalent and incident cases, with adulthood exposure being unassociated with incident arthritis. Across models, trauma exposure was associated with prevalent cases of both immune-related and osteoarthritis types. CONCLUSIONS: Higher lifetime trauma burden, especially during childhood, may predispose individuals to arthritis later in life. Early intervention or prevention efforts should identify trauma as an important risk factor for musculoskeletal health across the lifecourse.

A randomized cross-over study protocol to evaluate long-term gait training with a pediatric robotic exoskeleton outside the clinical setting in children with movement disorders.

Individuals with neuromuscular disorders display a combination of motor control deficits and lower limb weakness contributing to knee extension deficiency characterized by exaggerated stance phase knee flexion. There is a lack of evidence for long-term improvement of knee extension deficiency with currently available clinical treatment programs. Our previous work testing a wearable robotic exoskeleton with precisely timed assistive torque applied at the knee showed immediate increases in knee extension during walking for children with cerebral palsy, which continued to improve over an acute practice period. When we applied interleaved assistance and resistance to knee extension, we observed improvements in knee extension and increased muscle activation indicating the potential for muscle strengthening when used over time. There is a need for additional, high-quality trials to assess the impact of dosage, intensity and volume of training necessary to see persistent improvement in lower limb function for these patient populations. This randomized crossover study (ClinicalTrials.gov: NCT05726591) was designed to determine whether 12 weeks of overground gait training with a robotic exoskeleton outside of the clinical setting, following an initial in clinic accommodation period, has a beneficial effect on walking ability, muscle activity and overall motor function. Participants will be randomized to either complete the exoskeleton intervention or continue their standard therapy for 12 weeks first, followed by a crossover to the other study component. The primary outcome measure is change in peak knee extension angle during walking; secondary outcome measures include gait speed, strength, and validated clinical scales of motor function and mobility. Assessments will be completed before and after the intervention and at 6 weeks post-intervention, and safety and compliance will be monitored throughout. We hypothesize that the 12-week exoskeleton intervention outside the clinical setting will show greater improvements in study outcome measures than the standard therapy.