Citations

Abstract Purpose Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants’ motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers. Methods We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms. Results We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire self-reported receiving results they assessed as important, including negative findings, and 75.9% reported a form of health-related utility. Among a subset (19.4%) who shared their EGS reports, 16.6% (37 of n =223) received a monogenic finding and self-reported results deemed “important” were consistent with EGS reports. Most participants (74.1%) discussed their results with their family, but fewer discussed their results with a healthcare provider other than the site team (41.7%) or had one or more medical visits as a direct result of their EGS testing (23.1%). Participants expressed diverse motivations for EGS, with 91.4% expressing interest in their personal disease risk and 54% who expressed quasi-indication-based motivations related to family medical history. Individuals motivated by family history reported important results at a significantly higher rate. Conclusions Early adopters of EGS are motivated by general interest in their health as well as quasi-indication-based considerations such as family history. A majority of participants learned results they considered medically important, but a much smaller segment engaged healthcare providers with their results.

Aims Reliable assessment of joint stiffness is essential for studying arthrofibrosis in preclinical animal models. This study presents a new dedicated biomechanics device for measuring knee stiffness in mouse, rat, and rabbit models of arthrofibrosis, with the aim of validating its performance and comparing it to a previously validated device. Methods The new system integrates a torque load cell, stepper motor, and absolute encoder in a through-hole, unified configuration for precise continuous torque-angle measurement, with custom limb brackets ensuring species-specific alignment at the joint’s centre of rotation. To validate this device and compare it to a previously validated device, arthrofibrosis was induced using established models of extra-articular immobilization in mice and intra-articular violation with immobilization in rats and rabbits, followed by defined remobilization periods. Torque-angle curves were recorded ex vivo across species-specific torque ranges, and measurement variability between the new and a previous validated device was statistically compared using Brown-Forsythe’s test. Results The onset of hyperextension in contralateral limbs occurred at mean angles of 152.4° (mice), 154.4° (rats), and 152.8° (rabbits), and at maximum torque, mean flexion angles were 79.2°, 87.3°, and 140.5°, respectively. No significant differences in measurement variability were observed between devices across all species. Conclusion These findings demonstrate that our new device provides reproducible torque-angle data while maintaining the statistical robustness of the previous device and offering improved mechanical design and operational standardization. By enabling standardized, cross-species joint stiffness quantification, this platform improves cross-study comparability and strengthens the translational reliability of preclinical arthrofibrosis research. Cite this article: Bone Joint Res 2026;15(6):716–725.

Abstract Objective . The use of Feraheme (ferumoxytol) as a contrast agent in MR-guided focused ultrasound (MRgFUS) tumor ablations could enhance treatment safety and efficacy by improving vascular visualization through strong T1 and T2 shortening effects. However, Feraheme impact on MR thermometry and tissue heating is unclear. This study evaluates the feasibility of incorporating Feraheme into MRgFUS by assessing its impact on MR imaging contrast, MR thermometry, and thermal response in tissue-mimicking phantoms. Approach . Tissue-mimicking phantoms with 0 (baseline), 0.25, and 0.5 mM Feraheme concentrations were prepared using a validated recipe. Acoustic attenuation was measured with a commercial diagnostic ultrasound scanner. MR imaging at 1.5 T was performed to assess gradient-recalled-echo (GRE)-based thermometry signal-to-noise-ratio (SNR), relaxation rates, and relaxivities. MRgFUS system integrated with 1.5 T MRI was used to perform multiple sonications in the phantoms. Temperature elevations and focal heating areas were quantified from proton resonance frequency (PRF) shift thermometry. Experiments were repeated three times over the period of eight-weeks. Separately, temperature-dependent nuclear magnetic resonance (NMR) spectroscopy was performed at 3.0 T in saline-diluted Feraheme phantoms (0, 0.25, 0.5, and 1.0 mM) to assess the influence of Feraheme concentration on PRF coefficients used in MR thermometry. Main results . Phantoms showed nuclear relaxation times ( T 1: 1178.1 ± 77.8, T 2: 103.21 ± 2.45 ms) and attenuation coefficients (0.34–0.36 dB cm −1 MHz −1 ) within expected biological tissue ranges. Relaxivities demonstrated a strong linear dependence on Feraheme concentration ( r 1: 17.5 ± 0.2, r 2: 209.2 ± 2.6 s −1 mM −1 ). Relative to baseline (0 mM) phantom, the SNR of GRE-based thermometry increased by 12.6% at 0.25 mM and decreased by 27.1% at 0.5 mM. Sonications in Feraheme-containing phantoms resulted in statistically higher temperature elevations ( p < 0.001 ) although no statistically significant difference was observed between 0.25 and 0.5 mM. All NMR measurements demonstrated stable, linear PRF temperature dependence ( R 2 = 0.996–0.999), with PRF coefficients (between −0.0074 and −0.0082 ppm °C −1 ). The resulting thermometry bias was small and predictable (+0.67 and +1.73 per 20 °C at 3.0 T for 0.25 and 0.5 mM). Significance . These findings demonstrate that MR thermometry remains feasible at moderate Feraheme concentrations and support its potential use to enhance visualization of critical vasculature near targeted tissues during MRgFUS.

ABSTRACT The coexistence of obesity and insulin resistance is associated with elevated plasma amino acid concentrations. However, it remains unclear whether adiposity or insulin resistance is the stronger determinant of plasma amino acid dysregulation in this setting. Twenty-two adults (10 women, 12 men) spanning a broad range of body mass index (BMI) and insulin resistance underwent a 75-g oral glucose tolerance test (OGTT) after an overnight fast. Plasma glucose, insulin, and amino acid concentrations were measured serially, and insulin resistance/sensitivity was estimated from OGTT-derived glucose and insulin responses, using the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (Matsuda-ISI). Principal component analysis (PCA) of fasting plasma amino acid concentrations showed no clear separation by obesity or insulin resistance classifications. In contrast, PCA of OGTT-stimulated plasma amino acid concentrations revealed clearer clustering by BMI, fat mass, and waist circumference, whereas separation by HOMA-IR and Matsuda-ISI was less distinct. Importantly, regression analyses showed that BMI, fat mass, and waist circumference were significant predictors of OGTT-stimulated, but not fasting, amino acid responses, with waist circumference accounting for the greatest proportion of the variance in branched-chain amino acid responses during the OGTT (R 2 = 0.54). In conclusion, measures of adiposity, particularly total fat mass and waist circumference, accounted for a greater proportion of the variance in plasma amino acid responses under physiologically stimulated conditions than indices of insulin resistance. These findings support the view that plasma amino acid concentrations reflect adiposity-related metabolic alterations more strongly than insulin resistance.

ABSTRACT Background In healthy individuals, exercise and amino acid availability act synergistically to stimulate muscle anabolism. However, this interaction may be impaired in individuals with obesity. Objective We examined whether acute aerobic exercise alters amino acid-stimulated muscle protein synthesis during immediate postexercise recovery in adults with obesity. Methods Sixteen sedentary adults with a body mass index >30 kg/m 2 underwent a stable-isotope tracer infusion to measure mixed-muscle protein fractional synthesis rate (FSR) in the basal/fasted state and during an amino acid infusion, either with or without prior aerobic exercise. Participants were randomly assigned to receive either amino acid infusion alone (AA) or 45 min of cycling exercise at ∼65% heart rate reserve immediately before amino acid infusion (EX + AA). Results Amino acid infusion increased muscle protein FSR in the AA group ( P < 0.0001) but not in the EX + AA group ( P > 0.05), and the amino acid-stimulated increase in FSR was 78% lower in EX + AA than in AA ( P < 0.01). The amino acid infusion increased ( P < 0.05) plasma amino acid concentrations in both groups. However, during the amino acid infusion, plasma concentrations of essential and branched-chain amino acids, including leucine, were lower in EX + AA than in AA ( P < 0.05). Moreover, across participants, absolute changes in muscle protein FSR were positively associated with plasma leucine concentrations during the amino acid infusion ( P < 0.05). Conclusions These findings show that, in individuals with obesity, acute aerobic exercise markedly attenuates amino acid-stimulated muscle protein synthesis during early postexercise recovery. These findings have important implications for designing nutritional strategies to optimize muscle anabolism in this population.