Comparative toxicological assessment of two bisphenols using a systems approach: Evaluation of the behavioral and transcriptomic responses of Danio rerio to Bisphenol A and Tetrabromobisphenol A.

The zebrafish (Danio rerio) is becoming a critical component of New Approach Methods (NAMs) in chemical risk assessment. As a whole organism in vitro NAM, the zebrafish model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic approach not only allows for insight into mechanism of action for both apical endpoints and unobservable adverse outcomes, but also changes in gene expression induced by lower, environmentally relevant concentrations. In this study, we used a larval zebrafish model to assess the behavioral and transcriptomic alterations caused by sub-phenotypic concentrations of two chemicals with the same structural backbone, the endocrine disrupting chemicals: Bisphenol A and Tetrabromobisphenol A. Following assessment of behavioral toxicity, we used a transcriptomic approach to identify molecular pathways associated with previously described phenotypes. We also determined the transcriptomic Point of Departure (POD) for each chemical by modelling gene expression changes as continuous systems which allows for the identification of a single concentration at which toxic effects can be predicted. This can then be investigated with confirmatory cell-based testing in an integrated approach to testing and assessment (IATA) to determine risk to human health and the environment with greater confidence. This paper demonstrates the impact of using a multi-faceted approach for evaluating the physiological and neurotoxic effects of exposure to structurally related chemicals. By comparing phenotypic effects with transcriptomic outcomes, we were able to differentiate, characterize and rank the toxicities of related bisphenols, which demonstrates methodological advantages unique to the larval zebrafish NAM.

Using unstructured crowd-sourced data to evaluate urban tolerance of terrestrial native animal species within a California Mega-City.

In response to biodiversity loss and biotic community homogenization in urbanized landscapes, there are increasing efforts to conserve and increase biodiversity within urban areas. Accordingly, around the world, previously extirpated species are (re)colonizing and otherwise infiltrating urban landscapes, while other species are disappearing from these landscapes. Tracking the occurrence of traditionally urban intolerant species and loss of traditionally urban tolerant species should be a management goal of urban areas, but we generally lack tools to study this phenomenon. To address this gap, we first used species' occurrences from iNaturalist, a large collaborative dataset of species observations, to calculate an urban association index (UAI) for 967 native animal species that occur in the city of Los Angeles. On average, the occurrence of native species was negatively associated with our composite measure of urban intensity, with the exception of snails and slugs, which instead occur more frequently in areas of increased urban intensity. Next, we assessed 8,348 0.25 x 0.25 mile grids across the City of Los Angeles to determine the average grid-level UAI scores (i.e., a summary of the UAIs present in a grid cell, which we term Community Urban Tolerance Index or CUTI). We found that areas of higher urban intensity host more urban tolerant species, but also that taxonomic groups differ in their aggregate tolerance of urban areas, and that spatial patterns of tolerance vary between groups. The framework established here has been designed to be iteratively reevaluated by city managers of Los Angeles in order to track the progress of initiatives to preserve and encourage urban biodiversity, but can be rescaled to sample different regions within the city or different cities altogether to provide a valuable tool for city managers globally.

Immune system modulation & virus transmission during parasitism identified by multi-species transcriptomics of a declining insect biocontrol system.

BACKGROUND: The Argentine stem weevil (ASW, Listronotus bonariensis) is a significant pasture pest in Aotearoa New Zealand, primarily controlled by the parasitoid biocontrol agent Microctonus hyperodae. Despite providing effective control of ASW soon after release, M. hyperodae parasitism rates have since declined significantly, with ASW hypothesised to have evolved resistance to its biocontrol agent. While the parasitism arsenal of M. hyperodae has previously been investigated, revealing many venom components and an exogenous novel DNA virus Microctonus hyperodae filamentous virus (MhFV), the effects of said arsenal on gene expression in ASW during parasitism have not been examined. In this study, we performed a multi-species transcriptomic analysis to investigate the biology of ASW parasitism by M. hyperodae, as well as the decline in efficacy of this biocontrol system. RESULTS: The transcriptomic response of ASW to parasitism by M. hyperodae involves modulation of the weevil's innate immune system, flight muscle components, and lipid and glucose metabolism. The multispecies approach also revealed continued expression of venom components in parasitised ASW, as well as the transmission of MhFV to weevils during parasitism and some interrupted parasitism attempts. Transcriptomics did not detect a clear indication of parasitoid avoidance or other mechanisms to explain biocontrol decline. CONCLUSIONS: This study has expanded our understanding of interactions between M. hyperodae and ASW in a biocontrol system of critical importance to Aotearoa-New Zealand's agricultural economy. Transmission of MhFV to ASW during successful and interrupted parasitism attempts may link to a premature mortality phenomenon in ASW, hypothesised to be a result of a toxin-antitoxin system. Further research into MhFV and its potential role in ASW premature mortality is required to explore whether manipulation of this viral infection has the potential to increase biocontrol efficacy in future.

Peripheral canalicular branching is decreased in streptozotocin-induced diabetes and correlates with decreased whole-bone ultimate load and perilacunar elastic work.

Osteocytes, the most abundant cell type in bone, play a crucial role in mechanosensation and signaling for bone formation and resorption. These cells reside within a complex lacuno-canalicular network (OLCN). Osteocyte signaling is reduced under diabetic conditions, and both type 1 and type 2 diabetes lead to reduced bone turnover, perturbed bone composition, and increased fracture risk. We hypothesized that this reduced bone turnover, and altered bone composition with diabetes is associated with reduced OLCN architecture and connectivity. This study aimed to elucidate: (1) the sequence of OLCN changes with diabetes related to bone turnover and (2) whether changes to the OLCN are associated with tissue composition and mechanical properties. Twelve- to fourteen-week-old male C57BL/6 mice were administered streptozotocin at 50 mg/kg for 5 consecutive days to induce hyperglycemia, sacrificed at baseline (BL), or after being diabetic for 3 (D3) and 7 (D7) wk with age-matched (C3, C7) controls (n = 10-12 per group). Mineralized femoral sections were infiltrated with rhodamine, imaged with confocal microscopy, then the OLCN morphology and topology were characterized and correlated against bone histomorphometry, as well as local and whole-bone mechanics and composition. D7 mice exhibited a lower number of peripheral branches relative to C7. The total number of canalicular intersections (nodes) was lower in D3 and D7 relative to BL (P < 0.05 for all), and a reduced bone formation rate (BFR) was observed at D7 vs C7. The number of nodes explained only 15% of BFR, but 45% of Ct.BV/TV, and 31% of ultimate load. The number of branches explained 30% and 22% of the elastic work at the perilacunar and intracortical region, respectively. Collectively, the reduction in OLCN architecture and association of OLCN measures with bone turnover, mechanics, and composition highlights the relevance of the osteocyte and the OLCN and a potential therapeutic target for treating diabetic skeletal fragility.

Labral Augmentation With Either Iliotibial Band Allograft or Dermis Allograft Perform Similarly Regarding Peak Force, Displacement, and Work to Labral Repair in Suction Seal Restoration: A Biomechanical Study.

PURPOSE: To investigate whether allograft substitutes may be used to restore suctional seal properties with labral augmentation, the purpose of the current study was to evaluate the biomechanical properties of the labral suction seal under several scenarios, including: (1) intact labrum, (2) rim preparation, (3) labral repair, (4) labral augmentation with iliotibial band (ITB), and (5) labral augmentation with a dermis allograft. METHODS: Eleven hemi-pelvises were dissected to the level of the labrum and placed in a material testing system for biomechanical axial distraction. Each specimen was compressed to 250 newtons (N) and distracted at 10 mm/s while load, crosshead displacement, and time were continuously recorded. For each of the 5 labral states, 3 testing repetitions were performed. Peak force (N, newtons), displacement at peak force (mm, millimeter), and work (N-mm, newton, millimeter) were calculated and normalized to the intact state of each specimen. RESULTS: Eleven specimens were tested and 8 specimens (age: 58.6 ± 5.4 years, body mass index: 28.6 ± 6.8 kg/m2; 4 female patients; 5 right hips) were included in final analyses. Expressed as a percentage relative to the intact state, the average normalized peak force, displacement at peak force, and work for each labral state were as follows: intact (100.0% ± 0% for all), rim preparation (89.0% ± 9.2%, 93.3% ± 20.6%, 85.1% ± 9.0%), repair (61.3% ± 17.9%, 88.4% ± 36.9%, 58.1% ± 16.7%), ITB allograft (62.7% ± 24.9%, 83.9% ± 21.6%, 59.4% ± 22.4%), and dermis allograft (57.8% ± 27.2%, 88.2% ± 29.5%, 50.0% ± 20.1%). Regarding peak force, intact state was significantly greater compared with the labral repair, augmentation with ITB, and augmentation with the dermis allograft states (P < .001). No significant differences were demonstrated between displacement at peak force (P = .561). Regarding work, both intact state and rim preparation states were significantly greater than the repair, ITB augmentation, and dermis allograft augmentation states (P < .001). In all outcome measures, the dermis allograft augmentation performed with no statistical difference to the ITB augmentation state. CONCLUSIONS: Labral repair and labral augmentation with either ITB allograft or the dermis allograft resulted in significantly lower peak force and work to equilibrium compared with the intact and rim prep states. There was no statistical difference between repair and augmentation states as well as no statistical difference between ITB allograft and dermal allograft at time zero. CLINICAL RELEVANCE: This study compares biomechanical properties of the suction seal of the hip comparing labral states including intact, rim preparation, repair, and augmentation, which can be used for surgical decision-making.

Mating system induced lags in rates of range expansion for different simulated mating systems and dispersal strategies: a modelling study.

Mismatches between current and potential species distributions are commonplace due to lags in the response of populations to changing environmental conditions. The prevailing mating system may contribute to such lags where it leads to mating failure at the range edge, but how active dispersers might mitigate these lags using social information to inform dispersal strategies warrants greater exploration. We used an individual-based model to explore how different mating systems for species that actively search for habitat can impose a filter on the ability to colonise empty, fragmented landscapes, and explored how using social information during dispersal can mitigate the lags caused by more constrained mating systems. The mate-finding requirements implemented in two-sex models consistently led to slower range expansion compared to those that were not mate limited (i.e., female only models), even when mating was polygynous. A mate-search settlement strategy reduced the proportion of unmated females at the range edge but had little impact on rate of spread. In contrast, a negative density-dependent settlement strategy resulted in much faster spread, which could be explained by a greater number of long-distance dispersal events. Our findings suggest that even low rates of mating failure at the range edge can lead to considerable lags in range expansion, though dispersal strategies that favour colonising more distant, sparsely occupied habitat patches may effectively mitigate these lags.

A cloudy forecast for species distribution models: Predictive uncertainties abound for California birds after a century of climate and land-use change.

Correlative species distribution models are widely used to quantify past shifts in ranges or communities, and to predict future outcomes under ongoing global change. Practitioners confront a wide range of potentially plausible models for ecological dynamics, but most specific applications only consider a narrow set. Here, we clarify that certain model structures can embed restrictive assumptions about key sources of forecast uncertainty into an analysis. To evaluate forecast uncertainties and our ability to explain community change, we fit and compared 39 candidate multi- or joint species occupancy models to avian incidence data collected at 320 sites across California during the early 20th century and resurveyed a century later. We found massive (>20,000 LOOIC) differences in within-time information criterion across models. Poorer fitting models omitting multivariate random effects predicted less variation in species richness changes and smaller contemporary communities, with considerable variation in predicted spatial patterns in richness changes across models. The top models suggested avian environmental associations changed across time, contemporary avian occupancy was influenced by previous site-specific occupancy states, and that both latent site variables and species associations with these variables also varied over time. Collectively, our results recapitulate that simplified model assumptions not only impact predictive fit but may mask important sources of forecast uncertainty and mischaracterize the current state of system understanding when seeking to describe or project community responses to global change. We recommend that researchers seeking to make long-term forecasts prioritize characterizing forecast uncertainty over seeking to present a single best guess. To do so reliably, we urge practitioners to employ models capable of characterizing the key sources of forecast uncertainty, where predictors, parameters and random effects may vary over time or further interact with previous occurrence states.

Lactate- and immunomagnetic-purified hiPSC-derived cardiomyocytes generate comparable engineered cardiac tissue constructs.

Three-dimensional engineered cardiac tissue (ECT) using purified human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has emerged as an appealing model system for the study of human cardiac biology and disease. A recent study reported widely used metabolic (lactate) purification of monolayer hiPSC-CM cultures results in an ischemic cardiomyopathy-like phenotype compared with magnetic antibody-based cell sorting (MACS) purification, complicating the interpretation of studies using lactate-purified hiPSC-CMs. Herein, our objective was to determine if use of lactate relative to MACS-purified hiPSC-CMs affects the properties of resulting hiPSC-ECTs. Therefore, hiPSC-CMs were differentiated and purified using either lactate-based media or MACS. Global proteomics revealed that lactate-purified hiPSC-CMs displayed a differential phenotype over MACS hiPSC-CMs. hiPSC-CMs were then integrated into 3D hiPSC-ECTs and cultured for 4 weeks. Structurally, there was no significant difference in sarcomere length between lactate and MACS hiPSC-ECTs. Assessment of isometric twitch force and Ca2+ transient measurements revealed similar functional performance between purification methods. High-resolution mass spectrometry-based quantitative proteomics showed no significant difference in protein pathway expression or myofilament proteoforms. Taken together, this study demonstrates that lactate- and MACS-purified hiPSC-CMs generate ECTs with comparable structural, functional, and proteomic features, and it suggests that lactate purification does not result in an irreversible change in a hiPSC-CM phenotype.

Mass Spectrometry-Based Multiomics Identifies Metabolic Signatures of Sarcopenia in Rhesus Monkey Skeletal Muscle.

Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in "omics" technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offers new insights into the molecular mechanisms underlying sarcopenia for the evaluation and monitoring of a therapeutic treatment of sarcopenia.

Plasmid-encoded lactose metabolism and mobilized colistin resistance (mcr-9) genes in Salmonella enterica serovars isolated from dairy facilities in the 1980s.

Horizontal gene transfer by plasmids can confer metabolic capabilities that expand a host cell's niche. Yet, it is less understood whether the coalescence of specialized catabolic functions, antibiotic resistances and metal resistances on plasmids provides synergistic benefits. In this study, we report whole-genome assembly and phenotypic analysis of five Salmonella enterica strains isolated in the 1980s from milk powder in Munich, Germany. All strains exhibited the unusual phenotype of lactose-fermentation and encoded either of two variants of the lac operon. Surprisingly, all strains encoded the mobilized colistin resistance gene 9 (mcr-9), long before the first report of this gene in the literature. In two cases, the mcr-9 gene and the lac locus were linked within a large gene island that formed an IncHI2A-type plasmid in one strain but was chromosomally integrated in the other strain. In two other strains, the mcr-9 gene was found on a large IncHI1B/IncP-type plasmid, whereas the lac locus was encoded on a separate chromosomally integrated plasmidic island. The mcr-9 sequences were identical and genomic contexts could not explain the wide range of colistin resistances exhibited by the Salmonella strains. Nucleotide variants did explain phenotypic differences in motility and exopolysaccharide production. The observed linkage of mcr-9 to lactose metabolism, an array of heavy-metal detoxification systems, and other antibiotic resistance genes may reflect a coalescence of specialized phenotypes that improve the spread of colistin resistance in dairy facilities, much earlier than previously suspected.

Quantum-Enhanced Magnetometry at Optimal Number Density.

We study the use of squeezed probe light and evasion of measurement backaction to enhance the sensitivity and measurement bandwidth of an optically pumped magnetometer (OPM) at sensitivity-optimal atom number density. By experimental observation, and in agreement with quantum noise modeling, a spin-exchange-limited OPM probed with off-resonance laser light is shown to have an optimal sensitivity determined by density-dependent quantum noise contributions. Application of squeezed probe light boosts the OPM sensitivity beyond this laser-light optimum, allowing the OPM to achieve sensitivities that it cannot reach with coherent-state probing at any density. The observed quantum sensitivity enhancement at optimal number density is enabled by measurement backaction evasion.

Trans-Omics analysis of post injury thrombo-inflammation identifies endotypes and trajectories in trauma patients.

Understanding and managing the complexity of trauma-induced thrombo-inflammation necessitates an innovative, data-driven approach. This study leveraged a trans-omics analysis of longitudinal samples from trauma patients to illuminate molecular endotypes and trajectories that underpin patient outcomes, transcending traditional demographic and physiological characterizations. We hypothesize that trans-omics profiling reveals underlying clinical differences in severely injured patients that may present with similar clinical characteristics but ultimately have very different responses to treatment and clinical outcomes. Here we used proteomics and metabolomics to profile 759 of longitudinal plasma samples from 118 patients at 11 time points and 97 control subjects. Results were used to define distinct patient states through data reduction techniques. The patient groups were stratified based on their shock severity and injury severity score, revealing a spectrum of responses to trauma and treatment that are fundamentally tied to their unique underlying biology. Ensemble models were then employed, demonstrating the predictive power of these molecular signatures with area under the receiver operating curves of 80 to 94% for key outcomes such as INR, ICU-free days, ventilator-free days, acute lung injury, massive transfusion, and death. The molecularly defined endotypes and trajectories provide an unprecedented lens to understand and potentially guide trauma patient management, opening a path towards precision medicine. This strategy presents a transformative framework that aligns with our understanding that trauma patients, despite similar clinical presentations, might harbor vastly different biological responses and outcomes.

Mass spectrometry-based multi-omics identifies metabolic signatures of sarcopenia in rhesus monkey skeletal muscle.

Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in omics technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified numerous proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified multiple metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offer new insights into the molecular mechanism underlying sarcopenia for the evaluation and monitoring of therapeutic treatment of sarcopenia.

Bromodomain-containing Protein 4 regulates innate inflammation via modulation of alternative splicing.

Introduction: Bromodomain-containing Protein 4 (BRD4) is a transcriptional regulator which coordinates gene expression programs controlling cancer biology, inflammation, and fibrosis. In the context of airway viral infection, BRD4-specific inhibitors (BRD4i) block the release of pro-inflammatory cytokines and prevent downstream epithelial plasticity. Although the chromatin modifying functions of BRD4 in inducible gene expression have been extensively investigated, its roles in post-transcriptional regulation are not well understood. Given BRD4's interaction with the transcriptional elongation complex and spliceosome, we hypothesize that BRD4 is a functional regulator of mRNA processing. Methods: To address this question, we combine data-independent analysis - parallel accumulation-serial fragmentation (diaPASEF) with RNA-sequencing to achieve deep and integrated coverage of the proteomic and transcriptomic landscapes of human small airway epithelial cells exposed to viral challenge and treated with BRD4i. Results: We discover that BRD4 regulates alternative splicing of key genes, including Interferon-related Developmental Regulator 1 (IFRD1) and X-Box Binding Protein 1 (XBP1), related to the innate immune response and the unfolded protein response (UPR). We identify requirement of BRD4 for expression of serine-arginine splicing factors, splicosome components and the Inositol-Requiring Enzyme 1 IREα affecting immediate early innate response and the UPR. Discussion: These findings extend the transcriptional elongation-facilitating actions of BRD4 in control of post-transcriptional RNA processing via modulating splicing factor expression in virus-induced innate signaling.

Demographic consequences of phenological asynchrony for North American songbirds.

Changes in phenology in response to ongoing climate change have been observed in numerous taxa around the world. Differing rates of phenological shifts across trophic levels have led to concerns that ecological interactions may become increasingly decoupled in time, with potential negative consequences for populations. Despite widespread evidence of phenological change and a broad body of supporting theory, large-scale multitaxa evidence for demographic consequences of phenological asynchrony remains elusive. Using data from a continental-scale bird-banding program, we assess the impact of phenological dynamics on avian breeding productivity in 41 species of migratory and resident North American birds breeding in and around forested areas. We find strong evidence for a phenological optimum where breeding productivity decreases in years with both particularly early or late phenology and when breeding occurs early or late relative to local vegetation phenology. Moreover, we demonstrate that landbird breeding phenology did not keep pace with shifts in the timing of vegetation green-up over a recent 18-y period, even though avian breeding phenology has tracked green-up with greater sensitivity than arrival for migratory species. Species whose breeding phenology more closely tracked green-up tend to migrate shorter distances (or are resident over the entire year) and breed earlier in the season. These results showcase the broadest-scale evidence yet of the demographic impacts of phenological change. Future climate change-associated phenological shifts will likely result in a decrease in breeding productivity for most species, given that bird breeding phenology is failing to keep pace with climate change.

Three-Grade Magnetic Resonance Imaging-Based Gluteus Medius and/or Minimus Tear Classification System Provides Excellent Inter-Rater Reliability.

Purpose: To develop a magnetic resonance imaging (MRI)-based classification system integrating tear characteristics including tear thickness (partial vs full) and tear retraction (less than or greater than 2 cm) for gluteus medius and/or minimus tears and to determine the inter-rater reliability of this MRI-based classification for gluteus medius and/or minimus tears. Methods: Patients who underwent primary endoscopic or open repair of gluteus medius and/or minimus tears between 2012 and 2022 were identified to be included in the review of 1.5-T MRI scans. One hundred MRI scans were randomized for review by 2 orthopaedic surgeons and evaluated for tear thickness (partial vs full), extent of retraction, and degree of fatty infiltration according to an applied Goutallier-Fuchs (G-F) classification. Tears were also graded according to the 3-grade MRI-based classification system as follows: grade 1, partial-thickness tears; grade 2, full-thickness tears with less than 2 cm of retraction; grade 3, full thickness with 2 cm or more retraction. Inter-rater reliability was calculated by absolute and relative agreement using Cohen's kappa (κ). Significance was defined by P value <.05. Results: In total, 221 patients were identified, and after application of exclusion criteria and randomization, 100 scans were evaluated. The 3-grade classification system demonstrated high absolute agreement (88%) comparable to the absolute agreement of the G-F classification (67%). The 3-grade classification system demonstrated substantial inter-rater reliability (κ = 0.753), whereas the G-F classification demonstrated moderate inter-rater reliability (κ = 0.489). Conclusions: The proposed 3-grade MRI-based classification system for gluteus medius and/or minimus tears demonstrated substantial inter-rater reliability, comparable with that of the applied G-F classification. Clinical Relevance: It is important to understand how gluteus medius and/or minimus tear characteristics impact postoperative outcomes. The 3-grade MRI-based classification incorporates tear thickness and amount of retraction that can complement previous classification systems to give the provider and patient more information when considering treatment options.

Effect of Differing Orientation and Magnitude of Femoral Torsion on Outcomes and Achievement of the MCID and PASS at 5 Years After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

BACKGROUND: Femoral torsion measurements and outcomes are variable throughout the literature and have focused on short-term follow-up. However, there is a paucity of literature investigating clinically meaningful outcomes at midterm follow-up after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). PURPOSE: To quantify femoral version using computed tomography imaging in patients with FAIS and to explore the relationship between version abnormalities and 5-year outcomes after hip arthroscopy. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent primary hip arthroscopy for FAIS between January 2012 and November 2017 were identified. Patients were included if they had 5-year follow-up with completion of ≥1 patient-reported outcome (PRO) scores and excluded if they had Tönnis grade >1, revision hip surgery, a concomitant hip procedure, a developmental disorder, or a lateral center-edge angle <20°. Torsion groups were defined as severe retrotorsion (<0°), moderate retrotorsion (0.1°-5°), normal torsion (5.1°-20°), moderate antetorsion (20.1°-25°), and severe antetorsion (>25.1°) based on computed tomography measurements. Patient characteristics were analyzed among the torsion cohorts, as were preoperative and 5-year PROs: Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sports Subscale, modified Harris Hip Score, international Hip Outcome Tool, visual analog scale for pain, and visual analog scale for satisfaction. Achievement rates of cohort-specific thresholds for the minimal clinically important difference and Patient Acceptable Symptom State were calculated and compared among cohorts. RESULTS: A total of 362 patients (244 female, 118 male; mean ± SD age, 33.1 ± 11.5 years; body mass index, 26.9 ± 17.8) met inclusion/exclusion criteria and were analyzed at a final mean follow-up of 64.3 ± 9.4 months (range, 53.5-115.5 months). Mean femoral torsion was 12.8°± 9.2°. The number of patients within each group was 20 for severe retrotorsion (torsion, -6.3°± 4.9°), 45 for moderate retrotorsion (2.7°± 1.3°), 219 for normal torsion (12.2°± 4.1°), 39 for moderate antetorsion (21.9°± 1.3°), and 39 for severe antetorsion (29.0°± 4.2°). No significant differences in age, body mass index, sex, smoking status, workers' compensation, psychiatric history, back pain, or physical activity were found among the torsional groups. All groups demonstrated significant improvements at 5 years postoperatively (P < .01 for all). All torsion subgroups demonstrated similar pre- to postoperative changes in PROs (P≥ .515) and PRO values at 5-year follow-up (P≥ .098). There were no significant differences in the achievement of the minimal clinically important difference (P≥ .422) or Patient Acceptable Symptom State (P≥ .161) for any of the PROs among the torsion groups. CONCLUSION: The orientation and severity of femoral torsion at the time of hip arthroscopy for FAIS in this study's cohort did not affect the propensity for clinically meaningful outcome improvement at midterm follow-up.

The Contribution of Perilacunar Composition and Mechanical Properties to Whole-Bone Mechanical Outcomes in Streptozotocin-Induced Diabetes.

Osteocytes are the most abundant cell type in bone and remodel their local perilacunar matrix in response to a variety of stimuli and diseases. How the perilacunar composition and mechanical properties are affected by type 1 diabetes (T1D), and the contribution of these local changes to the decline in whole-bone functional properties that occurs with diabetes remains unclear. 12-14 week old C57/BL6 male mice were administered a series of low-dose streptozotocin injections and sacrificed at baseline (BL), 3 (D3) and 7 weeks (D7) following confirmation of diabetes, along with age-matched controls (C3, C7). Femora were then subjected to a thorough morphological (µCT), mechanical (four-point bending, nanoindentation), and compositional (HPLC for collagen cross-links, Raman spectroscopy) analysis at the whole-bone and local (perilacunar and intracortical) levels. At the whole-bone level, D7 mice exhibited 10.7% lower ultimate load and 26.4% lower post-yield work relative to C7. These mechanical changes coincided with 52.2% higher levels of pentosidine at D7 compared to C7. At the local level, the creep distance increased, while modulus and hardness decreased in the perilacunar region relative to the intracortical for D7 mice, suggesting a spatial uncoupling in skeletal adaptation. D7 mice also exhibited increased matrix maturity in the 1660/1690 cm-1 ratio at both regions relative to C7. The perilacunar matrix maturity was predictive of post-yield work (46%), but perilacunar measures were not predictive of ultimate load, which was better explained by cortical area (26%). These results show that diabetes causes local perilacunar composition perturbations that affect whole-bone level mechanical properties, implicating osteocyte maintenance of its local matrix in the progression of diabetic skeletal fragility.