Simulation and experimental benchmarking of a proton pencil beam scanning nozzle model for development of MR-integrated proton therapy.

BACKGROUND: MR-integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an magnetic resonance imaging (MRI) scanner. The magnetic interaction between these two components is deemed high risk as the MR images can be degraded if there is cross-talk during beam delivery and image acquisition. PURPOSE: To create and benchmark a self-consistent proton PBS nozzle model for empowering the next stages of MR-integrated proton therapy development, namely exploring and de-risking complete integrated prototype system designs including magnetic shielding of the PBS nozzle. MATERIALS AND METHODS: Magnetic field (COMSOL Multiphysics ${\text{Multiphysics}}$ ) and radiation transport (Geant4) models of a proton PBS nozzle located at OncoRay (Dresden, Germany) were developed according to the manufacturers specifications. Geant4 simulations of the PBS process were performed by using magnetic field data generated by the COMSOL Multiphysics ${\text{Multiphysics}}$ simulations. In total 315 spots were simulated which consisted of a 40 × 30 cm 2 $40\times 30\,{\text{cm}}^{2}$ scan pattern with 5 cm spot spacings and for proton energies of 70, 100, 150, 200, and 220 MeV. Analysis of the simulated deflection at the beam isocenter plane was performed to determine the self-consistency of the model. The magnetic fringe field from a sub selection of 24 of the 315 spot simulations were directly compared with high precision magnetometer measurements. These focused on the maximum scanning setting of ± $\pm$  20 cm beam deflection as generated from the second scanning magnet in the PBS for a proton beam energy of 220 MeV. Locations along the beam line central axis (CAX) were measured at beam isocenter and downstream of 22, 47, 72, 97, and 122 cm. Horizontal off-axis positions were measured at 22 cm downstream of isocenter ( ± $\pm$  50, ± $\pm$  100, and ± $\pm$  150 cm from CAX). RESULTS: The proton PBS simulations had good spatial agreement to the theoretical values in all 315 spots examined at the beam line isocenter plane (0-2.9 mm differences or within 1.5 % of the local spot deflection amount). Careful analysis of the experimental measurements were able to isolate the changes in magnetic fields due solely to the scanning magnet contribution, and showed 1.9  ± $\pm$  1.2 µ T $\bf{\mu} {\text{T}}$ -9.4 ± $\pm$  1.2 µ T $\bf{\mu} {\text{T}}$ changes over the range of measurement locations. Direct comparison with the equivalent simulations matched within the measurement apparatus and setup uncertainty in all but one measurement point. CONCLUSIONS: For the first time a robust, accurate and self-consistent model of a proton PBS nozzle assembly has been created and successfully benchmarked for the purposes of advancing MR-integrated proton therapy research. The model will enable confidence in further simulation based work on fully integrated designs including MRI scanners and PBS nozzle magnetic shielding in order to de-risk and realize the full potential of MR-integrated proton therapy.

Obesity- and diet-induced plasticity in systems that control eating and energy balance.

In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2-day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up-and-coming research in these areas that may be of special interest to those with a background in these fields. The overarching theme of this review addresses plasticity within the central and peripheral nervous systems that regulates and influences eating, emphasizing distinctions between healthy and disease states. This is by no means a comprehensive review because this is a broad and rapidly developing area. However, we have pointed out relevant reviews and primary articles throughout, as well as gaps in current understanding and opportunities for developments in the field.

Assessment of Prophylactic Antibiotic Coverage in Culture-positive Traumatic Open Fractures.

Guidelines provide varying recommendations for the prophylactic antimicrobial treatment of open fractures. This single-center, retrospective cohort study was conducted to determine how well an institutional prophylactic antibiotic protocol covered pathogens associated with open fractures. The authors included adult trauma patients with one or more open fractures and a positive culture from the site of the open fracture, and compared outcomes between patients who were covered by prophylactic antibiotics with patients not covered by prophylactic antibiotics. Of 957 patients evaluated, 75 were included, with 40 patients (53%) covered by the prophylactic antibiotics received. Multidrug-resistant pathogens were isolated in 23 (58%) patients covered versus 26 (74%) patients not covered (p = 0.128). The median time to positive culture was less in patients not covered by initial antibiotics compared with those who were covered (30.2 vs. 102.1 days; p = 0.003). Over half of the patients developed cultures with pathogens that were covered by their initial antibiotic prophylaxis. (Journal of Surgical Orthopaedic Advances 33(2):084-087, 2024).

Changes in Parent-Student Text Message and Phone Call Communication During the Transition to College as Predictors of Cannabis and Simultaneous Use During the First Year.

Parent communication can be protective against cannabis use among young adults. However, changes in parent-student communication frequency naturally occur during the transition from high school to college. Recent research suggests declines in parent-student communication frequency predict increased drinking and consequences during the first year of college, yet these effects on other risky behaviors are unknown. The current study investigated whether post-matriculation changes in frequency of texting/calling with parents predict cannabis use and simultaneous use of cannabis and alcohol, and whether pre-matriculation cannabis and simultaneous use predict changes in communication. First-year students (N = 287, 61.3% female, 50.9% White) reported cannabis and simultaneous use pre- and post-matriculation (T1 & T3) and changes in frequency of texting/calling their mother/father per day (T2). Negative binomial hurdle models examined whether T2 changes in communication frequency predicted T3 cannabis and simultaneous use, and logistic regression models examined whether T1 cannabis and simultaneous use predicted T2 changes in communication frequency. Results revealed that increasing (vs. decreasing) frequency of calling with mothers and texting with fathers was protective against cannabis use, whereas increasing frequency of calling with fathers was associated with greater risk of use. Changes in communication did not significantly predict simultaneous use, nor did pre-matriculation cannabis or simultaneous use predict changes in either mode of communication with parents during the college transition. These findings highlight that changes in mother and father communication may be both beneficial and detrimental to cannabis use depending on the parent and mode of communication. Implications for these findings are discussed.

Branched chain α-ketoacids aerobically activate HIF1α signaling in vascular cells.

Hypoxia-inducible factor 1α (HIF1α) is a master regulator of numerous biological processes under low oxygen tensions. Yet, the mechanisms and biological consequences of aerobic HIF1α activation by intrinsic factors, particularly in primary cells remain elusive. Here, we show that HIF1α signaling is activated in several human primary vascular cells under ambient oxygen tensions, and in vascular smooth muscle cells (VSMCs) of normal human lung tissue, which contributed to a relative resistance to further enhancement of glycolytic activity in hypoxia. Mechanistically, aerobic HIFα activation is mediated by paracrine secretion of three branched chain α-ketoacids (BCKAs), which suppress prolyl hydroxylase domain-containing protein 2 (PHD2) activity via direct inhibition and via lactate dehydrogenase A (LDHA)-mediated generation of L-2-hydroxyglutarate (L2HG). Metabolic dysfunction induced by BCKAs was observed in the lungs of rats with pulmonary arterial hypertension (PAH) and in pulmonary artery smooth muscle cells (PASMCs) from idiopathic PAH patients. BCKA supplementation stimulated glycolytic activity and promoted a phenotypic switch to the synthetic phenotype in PASMCs of normal and PAH subjects. In summary, we identify BCKAs as novel signaling metabolites that activate HIF1α signaling in normoxia and that the BCKA-HIF1α pathway modulates VSMC function and may be relevant to pulmonary vascular pathobiology.

Patient perceptions of and experiences with stigma using telehealth for opioid use disorder treatment: a qualitative analysis.

BACKGROUND: Patients with opioid use disorder (OUD) experience various forms of stigma at the individual, public, and structural levels that can affect how they access and engage with healthcare, particularly with medications for OUD treatment. Telehealth is a relatively new form of care delivery for OUD treatment. As reducing stigma surrounding OUD treatment is critical to address ongoing gaps in care, the aim of this study was to explore how telehealth impacts patient experiences of stigma. METHODS: In this qualitative study, we interviewed patients with OUD at a single urban academic medical center consisting of multiple primary care and addiction clinics in Oregon, USA. Participants were eligible if they had (1) at least one virtual visit for OUD between March 2020 and December 2021, and (2) a prescription for buprenorphine not exclusively used for chronic pain. We conducted phone interviews between October and December 2022, then recorded, transcribed, dual-coded, and analyzed using reflexive thematic analysis. RESULTS: The mean age of participants (n = 30) was 40.5 years (range 20-63); 14 were women, 15 were men, and two were transgender, non-binary, or gender-diverse. Participants were 77% white, and 33% had experienced homelessness in the prior six months. We identified four themes regarding how telehealth for OUD treatment shaped patient perceptions of and experiences with stigma at the individual (1), public (2-3), and structural levels (4): (1) Telehealth offers wanted space and improved control over treatment setting; (2) Public stigma and privacy concerns can impact both telehealth and in-person encounters, depending on clinical and personal circumstances; (3) The social distance of telehealth could mitigate or exacerbate perceptions of clinician stigma, depending on both patient and clinician expectations; (4) The increased flexibility of telehealth translated to perceptions of increased clinician trust and respect. CONCLUSIONS: The forms of stigma experienced by individuals with OUD are complex and multifaceted, as are the ways in which those experiences interact with telehealth-based care. The mixed results of this study support policies allowing for a more individualized, patient-centered approach to care delivery that allows patients a choice over how they receive OUD treatment services.

Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.

In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2-/-) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2-/- fibers present deficits in force production and calcium sensitivity. Structurally, passive C2-/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2-/-, which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.

Neighborhood physical environments and change in cardiometabolic risk factors over 14 years in the study of Women's health across the nation.

BACKGROUND: Neighborhood physical environments may influence cardiometabolic health, but prior studies have been inconsistent, and few included long follow-up periods. METHODS: Changes in cardiometabolic risk factors were measured for up to 14 years in 2830 midlife women in the Study of Women's Health Across the Nation, a multi-ethnic/racial cohort of women from seven U.S. sites. Data on neighborhood food retail environments (modified Retail Food Environment Index) and walkability (National Walkability Index) were obtained for each woman's residence at each follow-up. Data on neighborhood access to green space, parks, and supermarkets were available for subsets (32-42%) of women. Models tested whether rates of change in cardiometabolic outcomes differed based on neighborhood characteristics, independent of sociodemographic and health-related covariates. RESULTS: Living in more (vs. less) walkable neighborhoods was associated with favorable changes in blood pressure outcomes (SBP: -0.27 mmHg/year, p = 0.002; DBP: -0.22 mmHg/year, p < 0.0001; hypertension status: ratio of ORs = 0.79, p < 0.0001), and small declines in waist circumference (-0.09 cm/year, p = 0.03). Small-magnitude associations were also observed between low park access and greater increases in blood pressure outcomes (SBP: 0.37 mmHg/year, p = 0.003; DBP: 0.15 mmHg/year, p = 0.04; hypertension status: ratio of ORs = 1.16, p = .04), though associations involving DBP and hypertension were only present after adjustment for sociodemographic variables. Other associations were statistically unreliable or contrary to hypotheses. CONCLUSION: Neighborhood walkability may have a meaningful influence on trajectories of blood pressure outcomes in women from midlife to early older adulthood, suggesting the need to better understand how individuals interact with their neighborhood environments in pursuit of cardiometabolic health.

Performance of HER2 DAKO HercepTest and Ventana 4B5 immunohistochemical assays on detecting HER2 gene-amplification in uterine serous carcinomas.

We compared the performance of two commonly-used HER2 immunohistochemistry (IHC) assays in uterine serous carcinomas (USC), correlating with HER2 gene amplification by fluorescence in-situ hybridization (FISH). Sixty-five USCs were stained by both HercepTest™ and PATHWAY 4B5 assays. FISH was performed by HER2 IQFISH pharmDx. Consensus HER2 IHC scoring was performed, and HER2 testing results were evaluated using USC-specific criteria. Complete concordance between HercepTest and 4B5 assays was achieved in 44/65 tumors (68%). The overall HER2 IHC/FISH concordance was 94% (45/48) by HercepTest and 91% (42/46) by 4B5. All HER2 IHC 3+ cases with HercepTest (n = 6) and 4B5 (n = 4) were gene-amplified, corresponding to specificities of 100%. For cases with IHC 2+, 41% (7/17) by HercepTest and 42% (8/19) by 4B5 had HER2 gene amplification. The sensitivity for HercepTest and 4B5 were 38% and 25%, respectively, at a cut-off of IHC 3+ (P = 0.50), and were 81% and 75%, respectively, at a cut-off of IHC 2+ (P > 0.99). Among HER2 IHC 0-1+ cases, 3/42 cases by HercepTest and 4/42 cases by 4B5 showed amplified FISH results, corresponding to overall false negative rates of 19% for HercepTest and 25% for 4B5. By using USC-specific IHC scoring criteria, both HercepTest and 4B5 assays showed high specificities (100%) for HER2 gene amplification in IHC 3+ cases, high IHC/FISH concordance, and comparable sensitivity for detecting HER2 gene amplification. The notable false negative rates using IHC 2+ as a cut-off for reflexing FISH analysis may warrant consideration for performing FISH in IHC 1+ cases until more data become available.

Population-level gene expression can repeatedly link genes to functions in maize.

Transcriptome-wide association studies (TWAS) can provide single gene resolution for candidate genes in plants, complementing genome-wide association studies (GWAS) but efforts in plants have been met with, at best, mixed success. We generated expression data from 693 maize genotypes, measured in a common field experiment, sampled over a 2-h period to minimize diurnal and environmental effects, using full-length RNA-seq to maximize the accurate estimation of transcript abundance. TWAS could identify roughly 10 times as many genes likely to play a role in flowering time regulation as GWAS conducted data from the same experiment. TWAS using mature leaf tissue identified known true-positive flowering time genes known to act in the shoot apical meristem, and trait data from a new environment enabled the identification of additional flowering time genes without the need for new expression data. eQTL analysis of TWAS-tagged genes identified at least one additional known maize flowering time gene through trans-eQTL interactions. Collectively these results suggest the gene expression resource described here can link genes to functions across different plant phenotypes expressed in a range of tissues and scored in different experiments.

Breast Cancer With HER2 Immunohistochemical Score 2 and Average HER2 Signals/Cell 6 or More and HER2/CEP17 Ratio Less Than 2 ('ISH Group 3'): A Multiinstitutional Cohort Analysis Emphasizing Outcome and Molecular Subtype.

Breast cancer (BC) with average human epidermal growth factor receptor 2 (HER2) signals/cell ≥6 and HER2/chromosome enumeration probe 17 (CEP17) ratio <2 (in situ hybridization [ISH] group 3) is very rare, accounting for 0.4% to 3.0% of cases sent for the dual-probe ISH assay. Although such patients are currently eligible for treatment with HER2-targeted therapy, their characteristics and outcomes remain poorly understood. Sixty-two BCs with equivocal HER2 immunohistochemical score (2+) and reflex ISH group 3 results were identified across 4 institutions. Available clinicopathologic characteristics, MammaPrint and BluePrint molecular results, and follow-up information were retrospectively analyzed. Most BCs with HER2 equivocal immunohistochemical and ISH group 3 results were histologic grade 2 or 3 (100%), estrogen receptor (ER) positive (90.3%), with an average HER2 signals/cell of 7.3. Molecular profiles revealed that 80% (16/20) of tumors were luminal subtypes, and HER2 molecular subtype was identified in 10% of tumors (2/20). Twelve (19.4%) out of 62 patients developed local recurrence and/or distant metastasis with a median follow-up of 50 months. One (10%) of 10 patients achieved pathologic complete response after neoadjuvant chemotherapy. Forty-nine (79%) out of 62 patients completed anti-HER2 agents, and exploratory analysis showed no statistically significant difference in disease outcomes between patients who completed anti-HER2 treatment and those who did not. Univariate analysis revealed advanced clinical stage, and ER/progesterone receptor negativity was associated with unfavorable disease outcomes, and exploratory multivariate analysis demonstrated that clinical stage was the most significant factor associated with disease outcomes in the studied population. These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.

Associations of Internal Medicine Residency Milestone Ratings and Certification Examination Scores With Patient Outcomes.

Importance: Despite its importance to medical education and competency assessment for internal medicine trainees, evidence about the relationship between physicians' milestone residency ratings or the American Board of Internal Medicine's initial certification examination and their hospitalized patients' outcomes is sparse. Objective: To examine the association between physicians' milestone ratings and certification examination scores and hospital outcomes for their patients. Design, Setting, and Participants: Retrospective cohort analyses of 6898 hospitalists completing training in 2016 to 2018 and caring for Medicare fee-for-service beneficiaries during hospitalizations in 2017 to 2019 at US hospitals. Main Outcomes and Measures: Primary outcome measures included 7-day mortality and readmission rates. Thirty-day mortality and readmission rates, length of stay, and subspecialist consultation frequency were also assessed. Analyses accounted for hospital fixed effects and adjusted for patient characteristics, physician years of experience, and year. Exposures: Certification examination score quartile and milestone ratings, including an overall core competency rating measure equaling the mean of the end of residency milestone subcompetency ratings categorized as low, medium, or high, and a knowledge core competency measure categorized similarly. Results: Among 455 120 hospitalizations, median patient age was 79 years (IQR, 73-86 years), 56.5% of patients were female, 1.9% were Asian, 9.8% were Black, 4.6% were Hispanic, and 81.9% were White. The 7-day mortality and readmission rates were 3.5% (95% CI, 3.4%-3.6%) and 5.6% (95% CI, 5.5%-5.6%), respectively, and were 8.8% (95% CI, 8.7%-8.9%) and 16.6% (95% CI, 16.5%-16.7%) for mortality and readmission at 30 days. Mean length of stay and number of specialty consultations were 3.6 days (95% CI, 3.6-3.6 days) and 1.01 (95% CI, 1.00-1.03), respectively. A high vs low overall or knowledge milestone core competency rating was associated with none of the outcome measures assessed. For example, a high vs low overall core competency rating was associated with a nonsignificant 2.7% increase in 7-day mortality rates (95% CI, -5.2% to 10.6%; P = .51). In contrast, top vs bottom examination score quartile was associated with a significant 8.0% reduction in 7-day mortality rates (95% CI, -13.0% to -3.1%; P = .002) and a 9.3% reduction in 7-day readmission rates (95% CI, -13.0% to -5.7%; P < .001). For 30-day mortality, this association was -3.5% (95% CI, -6.7% to -0.4%; P = .03). Top vs bottom examination score quartile was associated with 2.4% more consultations (95% CI, 0.8%-3.9%; P < .003) but was not associated with length of stay or 30-day readmission rates. Conclusions and Relevance: Among newly trained hospitalists, certification examination score, but not residency milestone ratings, was associated with improved outcomes among hospitalized Medicare beneficiaries.

Ectoparasites of the Critically Endangered green sawfish Pristis zijsron and sympatric elasmobranchs in Western Australia.

This study reports the metazoan ectoparasite fauna of juvenile Critically Endangered green sawfish, Pristis zijsron, and sympatric elasmobranchs in Western Australia. Five parasite taxa were found on 76 screened P. zijsron: Caligus furcisetifer (Copepoda: Caligidae), Dermopristis pterophila (Monogenea: Microbothriidae), Branchellion plicobranchus and Stibarobdella macrothela (Hirudinea: Piscicolidae), and praniza larvae of an unidentified gnathiid isopod. Only C. furcisetifer and D. pterophila were common, exhibiting discrepant site-specificity, with C. furcisetifer occurring mostly on the head and rostrum, and D. pterophila around the pectoral and pelvic fins. Intensity of infection for C. furcisetifer and D. pterophila increased with host total length and was influenced by host sex, but in opposite directions; intensity of C. furcisetifer was greater on female P. zijsron, whereas intensity of D. pterophila was greater on males. In the Ashburton River, likelihood of infection for C. furcisetifer and D. pterophila on P. zijsron increased with time since substantial freshwater discharge events, suggesting decreased salinity impacts both taxa. In addition to P. zijsron, five other sympatric elasmobranch species were opportunistically screened for ectoparasites in the study area: the giant shovelnose ray, Glaucostegus typus, the eyebrow wedgefish, Rhynchobatus palpebratus, the nervous shark, Carcharhinus cautus, the lemon shark, Negaprion acutidens, and the graceful shark, Carcharhinus amblyrhynchoides. Caligus furcisetifer was found on R. palpebratus; no other parasites of P. zijsron were found on other sympatric elasmobranch species. Conversely, Perissopus dentatus (Copepoda: Pandaridae) was found on all three carcharhinids but not on batoid rays (P. zijsron, G. typus or R. palpebratus).

pREBOA vs ER-REBOA impact on blood utilization and resuscitation requirements: A pilot analysis.

BACKGROUND: Partial occlusion of the aorta is a resuscitation technique designed to maximize proximal perfusion while allowing a graduated amount of distal flow to reduce the ischemic sequelae associated with complete aortic occlusion. The pREBOA catheter affords the ability to titrate perfusion as hemodynamics allows, however, the impact of this new technology for REBOA on blood use and other resuscitative requirements is currently unknown. We hypothesize pREBOA's ability to provide partial occlusion, when appropriate, decreases overall resuscitative requirements when compared to ER-REBOA. METHODS: The entire AAST AORTA Registry was used to compare resuscitation requirements between all ER-REBOA and pREBOA. Unpaired t-tests were used to compare resuscitation strategies including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, crystalloids, and need for pressors. RESULTS: When comparing ER-REBOA (n=800) use to pREBOA (n=155), initial patient presentations were similar except for age (44 vs 40 p=0.026) and rates of blunt injury (78.4% vs 78.7% p<0.010). Zone-1 occlusion was used less often in ER-REBOA (65.8 vs 71.7 p=0.046). Partial occlusion was performed in 85% of pREBOA compared to 11% in ER-REBOA (p<0.050). Vitals at the time of REBOA were worse in ER-REBOA, and received significantly more units of PRBCs, FFP, platelets, and liters of crystalloids than pREBOA (p<0.05). Rates of ARDS and septic shock were lower in pREBOA (p<0.05). CONCLUSION: When comparing pREBOA to ER-REBOA, there has been a rise in Zone-1 and partial occlusion. In our pilot analysis of the AORTA Registry, there was a reduction in administration of pRBC, FFP, platelets, and crystalloids. Though further prospective studies are required, this is the first to demonstrate an association between pREBOA, partial occlusion, and reduced blood use and resuscitative requirements.

Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle.

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere "C-zone," MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development, and promoting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility from the C-zone? Globular domains critical to MyBP-C's modulatory functions are absent from MyBP-H, suggesting MyBP-H may be functionally silent. However, our results suggest an active role. Small angle x-ray diffraction of intact larval tails revealed MyBP-H contributes to the compression of the myofilament lattice accompanying stretch or contraction, while in vitro motility experiments indicate MyBP-H shares MyBP-C's capacity as a molecular "brake". These results provide new insights and raise questions about the role of the C-zone during muscle development.

Prediction of Achilles Tendon Force During Common Motor Tasks From Markerless Video.

Remodeling of the Achilles tendon (AT) is partly driven by its mechanical environment. AT force can be estimated with neuromusculoskeletal (NMSK) modeling; however, the complex experimental setup required to perform the analyses confines use to the laboratory. We developed task-specific long short-term memory (LSTM) neural networks that employ markerless video data to predict the AT force during walking, running, countermovement jump, single-leg landing, and single-leg heel rise. The task-specific LSTM models were trained on pose estimation keypoints and corresponding AT force data from 16 subjects, calculated via an established NMSK modeling pipeline, and cross-validated using a leave-one-subject-out approach. As proof-of-concept, new motion data of one participant was collected with two smartphones and used to predict AT forces. The task-specific LSTM models predicted the time-series AT force using synthesized pose estimation data with root mean square error (RMSE) ≤ 526 N, normalized RMSE (nRMSE) ≤ 0.21 , R 2 ≥ 0.81 . Walking task resulted the most accurate with RMSE = 189±62 N; nRMSE = 0.11±0.03 , R 2 = 0.92±0.04 . AT force predicted with smartphones video data was physiologically plausible, agreeing in timing and magnitude with established force profiles. This study demonstrated the feasibility of using low-cost solutions to deploy complex biomechanical analyses outside the laboratory.

Postoperative Opioid-Prescribing Practice in Limb Preservation Surgery.

BACKGROUND: Limb preservation surgery affects more than 100,000 Americans annually. Current postoperative pain management prescribing practices of podiatric physicians in the United States are understudied. We examined prescribing practices for limb preservation surgery to identify prescriber characteristics' that may be associated with postoperative opioid-prescribing practices. METHODS: We administered an anonymous online questionnaire consisting of five patient scenarios with limb preservation surgery commonly performed by podiatric physicians. Respondents provided information about their prescription choice for each surgery. Basic provider demographics were collected. We developed linear regression models to identify the strength and direction of association between prescriber characteristics and quantity of postoperative opioid "pills" (dosage units) prescribed at surgery. Logistic regression models were used to identify the odds of prescribing opioids for each scenario. RESULTS: One hundred fifteen podiatric physicians completed the survey. Podiatric physicians reported using regional nerve blocks 70% to 88% of the time and prescribing opioids 43% to 67% of the time across all scenarios. Opioids were more commonly prescribed than nonsteroidal anti-inflammatory drugs and anticonvulsants. Practicing in the Northeast United States was a significant variable in linear regression (P = .009, a decrease of 9-10 dosage units) and logistic regression (odds ratio, 0.23; 95% confidence interval, 0.07-0.68; P = .008) models for the transmetatarsal amputation scenario. CONCLUSIONS: Prescribing practice variation exists in limb preservation surgery by region. Podiatric physicians reported using preoperative regional nerve blocks more than prescribing postoperative opioids for limb preservation surgeries. Through excess opioid prescribing, the diabetes pandemic has likely contributed to the US opioid epidemic. Podiatric physicians stand at the intersection of these two public health crises and are equipped to reduce their impact via preventive foot care and prescribing nonopioid analgesics when warranted.

Ecological validity of common behavioral decision making tasks: evidence across two samples.

BACKGROUND: Clinicians and scholars routinely use behavioral decision tasks to assess real-world decision making capabilities. However, many common behavioral decision making tasks lack data on the extent to which they predict real-world risky behaviors. Across two pre-registered studies, and two timepoints, we assessed decision making abilities using common behavioral tasks and predicted participants' real-world risky decision making from task performance. METHOD: In Study 1, 918 Mechanical Turk (MTurk) workers completed three decision making tasks in addition to assessments of real-world risk behavior: preventive health behaviors, COVID-19 vaccination status, and virtual social distancing task performance. In Study 2, 221 college student participants completed the Study 1 tasks plus additional assessments of decision making and real world risk and protective behaviors. RESULTS: Across both studies, the selected behavioral decision tasks rarely predicted real world behavior and, when they did, the relationship was weak at best. CONCLUSIONS: These data suggest that these behavioral decision making tasks may not be good predictors of real world risky behavior at present, with some evidence that the specificity of the behavior being assessed matters (i.e. the closer the task was to the specific behavior being predicted), calling for additional ecological validity research, with a greater variety of tasks in the future.

Which aspects of education are health protective? a life course examination of early education and adulthood cardiometabolic health in the 30-year study of early child care and Youth Development (SECCYD).

BACKGROUND: Past research describes robust associations between education and health, yet findings have generally been limited to the examination of education as the number of years of education or educational attainment. Little is known about the specific features or processes underpinning education that are health protective. The objective of the current study was to address this gap by examining specific aspects of early education pertaining to student characteristics and experiences, as well as features of the classroom environment, in predicting cardiometabolic health in adulthood. METHODS: Subjects were 1364 participants in the NICHD Study of Early Child Care and Youth Development (SECCYD, 1991-2009) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE, 2018-2022). Models examined individual education indicators (student social skills, student-teacher relationship quality, and classroom emotional and instructional quality in the period of elementary school and student academic performance between ages 54 months and 15 years) in relation to a composite of cardiometabolic risk in adulthood (ages 26-31), reflecting central adiposity, blood pressure, insulin resistance, inflammation, and dyslipidemia. Models were adjusted for key explanatory factors including socio-demographics, infant characteristics, parental socioeconomic status (SES), and child health status. Follow-up analyses were performed to test potential mediators of early education effects on adult health, including adult SES (educational attainment, household income) and health behaviors (diet quality, activity level, sleep duration, smoking). RESULTS: In adjusted models, results showed greater student social skills, indexed by a mean of annual teacher ratings between kindergarten and 6th grade, predicted lower cardiometabolic risk in adulthood (ß=-0.009, p <.05). In follow-up analyses, results showed the protective effect of student social skills on cardiometabolic risk may be mediated by adult income (ß=-0.0014, p <.05) and diet quality (ß=-0.0031, p <.05). Effects of the other early education indicators were non-significant (ps > 0.05). CONCLUSIONS: Findings point to the potential significance of early student social competence as a link to long-term health, possibly via the acquisition of resources needed for the maintenance of health, as well as through engagement in health behaviors supporting healthy eating. However, more research is needed to replicate these findings and to elaborate on the role of early student social competence and the pathways explaining its effects on cardiometabolic health in adulthood.