GPRC6A is a Potential Therapeutic Target for Metformin Regulation of Glucose Homeostasis in Mice.

Understanding the mechanism of metformin actions in treating type 2 diabetes is limited by an incomplete knowledge of the specific protein targets mediating its metabolic effects. Metformin has structural similarities to L-Arginine (2-amino-5-guanidinopentanoic acid), which is a ligand for GPRC6A, a Family C G-protein coupled receptor that regulates energy metabolism. Ligand activation of GPRC6A results in lowering of blood glucose and other metabolic changes resembling the therapeutic effect of metformin. In the current study, we tested if metformin activates GPRC6A. We used Alphafold2 to develop a structural model for L-Arginine (L-Arg) binding to the extracellu-lar bilobed venus flytrap domain (VFT) of GPRC6A. We found that metformin docked to the site in the VFT that overlaps the binding site for L-Arg. Metformin resulted in a dose-dependent stimulation of GPRC6A activity in HEK-293 cells transfected with full-length wild-type GPRC6A but not in untransfected control cells. In addition, metformin failed to activate an alternatively spliced GPRC6A isoform lacking the putative binding site in the VFT. More specifically, mutation of the predicted metformin key binding residues Glu170 and Asp303 in the GPRC6A VFT resulted in loss of metformin receptor activation in vitro. The in vivo role of GPRC6A in mediating the effects of metformin was tested in Gprc6a-/- mice. Administration of therapeutic doses of metformin lowered blood glucose levels following a glucose tolerance test in wild-type but not Gprc6a-/- mice. Finally, we EN300, created by adding a carboxymethyl group from L-Arg to the biguanide backbone of metformin. EN300 showed dose-dependent stimulation of GPRC6A activity in vitro with greater potency than L-Arginine, but less than metformin. Thus, we suggest that GPRC6A is a potential molecular target for metformin which may be used to understand the therapeutic actions of metformin and develop novel small molecules to treat T2D.

A Transient Iron Carbide Generated by Cyaphide Cleavage.

Despite their potential relevance as molecular models for industrial and biological catalysis, well-defined mononuclear iron carbide complexes are unknown, in part due to the limited number of appropriate C1 synthons. Here, we show the ability of the cyaphide anion (C≡P-) to serve as a C1 source. The high spin (S = 2) cyaphide complex PhB(tBuIm)3Fe-C≡P (PhB(tBuIm)3- = phenyl(tris(3-tert-butylimidazol-2-ylidene)borate) is readily accessed using the new cyaphide transfer reagent [Mg(DippNacNac)(CP)]2 (DippNacNac = CH{C(CH3)N(Dipp)}2 and Dipp = 2,6-di(iso-propyl)phenyl). Phosphorus atom abstraction is effected by the three-coordinate Mo(III) complex Mo(NtBuAr)3 (Ar = 3,5-Me2C6H3), which produces the known phosphide (tBuArN)3Mo≡P along with a transient iron carbide complex PhB(tBuIm)3Fe≡C. Electronic structure calculations reveal that PhB(tBuIm)3Fe≡C adopts a doublet ground state with nonzero spin density on the carbide ligand. While isolation of this complex is thwarted by rapid dimerization to afford the corresponding diiron ethynediyl complex, the carbide can be intercepted by styrene to provide an iron alkylidene.

Molecular-level design of alternative media for energy-saving pilot-scale fibrillation of nanocellulose.

The outstanding mechanical properties, light weight, and biodegradability of cellulose nanofibrils (CNFs) make them promising components of renewable and sustainable next-generation reinforced composite biomaterials and bioplastics. Manufacturing CNFs at a pilot scale requires disc-refining fibrillation of dilute cellulose fibers in aqueous pulp suspensions to shear the fibers apart into their nanodimensional forms, which is, however, an energy-intensive process. Here, we used atomistic molecular dynamics (MD) simulation to examine media that might facilitate the reduction of interactions between cellulose fibers, thereby reducing energy consumption in fibrillation. The most suitable medium found by the simulations was an aqueous solution with 0.007:0.012 wt.% NaOH:urea, and indeed this was found in pilot-scale experiments to reduce the fibrillation energy by ~21% on average relative to water alone. The NaOH:urea-mediated CNFs have similar crystallinity, morphology, and mechanical strength to those formed in water. The NaOH and urea act synergistically on CNFs to aid fibrillation but at different length scales. NaOH deprotonates hydroxyl groups leading to mesoscale electrostatic repulsion between fibrils, whereas urea forms hydrogen bonds with protonated hydroxyl groups thus disrupting interfibril hydrogen bonds. This suggests a general mechanism in which an aqueous medium that contains a strong base and a small organic molecule acting as a hydrogen-bond acceptor and/or donor may be effectively employed in materials processes where dispersion of deprotonable polymers is required. The study demonstrates how atomic-detail computer simulation can be integrated with pilot-scale experiments in the rational design of materials processes for the circular bioeconomy.

TCR-H: explainable machine learning prediction of T-cell receptor epitope binding on unseen datasets.

Artificial-intelligence and machine-learning (AI/ML) approaches to predicting T-cell receptor (TCR)-epitope specificity achieve high performance metrics on test datasets which include sequences that are also part of the training set but fail to generalize to test sets consisting of epitopes and TCRs that are absent from the training set, i.e., are 'unseen' during training of the ML model. We present TCR-H, a supervised classification Support Vector Machines model using physicochemical features trained on the largest dataset available to date using only experimentally validated non-binders as negative datapoints. TCR-H exhibits an area under the curve of the receiver-operator characteristic (AUC of ROC) of 0.87 for epitope 'hard splitting' (i.e., on test sets with all epitopes unseen during ML training), 0.92 for TCR hard splitting and 0.89 for 'strict splitting' in which neither the epitopes nor the TCRs in the test set are seen in the training data. Furthermore, we employ the SHAP (Shapley additive explanations) eXplainable AI (XAI) method for post hoc interrogation to interpret the models trained with different hard splits, shedding light on the key physiochemical features driving model predictions. TCR-H thus represents a significant step towards general applicability and explainability of epitope:TCR specificity prediction.

Inclusion of genital, sexual, and gender diversity in human reproductive teaching: impact on student experience and recommendations for tertiary educators.

Western societal norms have long been constrained by binary and exclusionary perspectives on matters such as infertility, contraception, sexual health, sexuality, and gender. These viewpoints have shaped research and knowledge frameworks for decades and led to an inaccurate and incomplete reproductive biology curriculum. To combat these deficiencies in reproductive systems-related education, our teaching team undertook a gradual transformation of unit content from 2018 to 2023, aiming to better reflect real diversity in human reproductive biology. This initiative involved intentional modifications, including clear use of pronoun self-identification by staff. We addressed the historical lack of representation of genital variation and helped students interrogate oversimplified reproductive biology binaries. A novel assignment was also introduced, prompting students to apply reproductive physiology knowledge to propose innovative assisted reproductive technology solutions for diverse demographics. The collective impact of these innovations had a positive effect on student learning. With improved lecture content and inclusive language, the proportion of inclusive group assignment topics chosen by students more than doubled in 2021. By 2022, coinciding with assessment topic changes, the percentage of inclusive assignments topics surpassed 50%. Further development of laboratory activities on intersex genital variation and genital modification raised further understanding of genital, sexual, gender, and cultural diversity. While implementing these changes posed challenges, pushing both staff and students out of their comfort zones at times, collaboration with relevant organizations and individuals with lived experience of queer identity proved integral. Ultimately, these relatively simple adjustments had a substantial impact on student experiences and appreciation for diversity.NEW & NOTEWORTHY We outline the teaching innovations that we have implemented to improve inclusion of diversity in reproductive biology and physiology contexts. This includes improved representation of genital, sexual, and gender diversity considerations in the curriculum. There is a critical need for these innovations as how we teach fundamentally shapes the understanding of our future medical and health professionals and researchers and thus influences the quality of future medical care and research.

Emerging Patterns of Foot and Ankle Injuries in Pickleball Players: A Short Report.

BACKGROUND: Pickleball's surging popularity has driven an increase in injuries presenting to medical providers. This study seeks to describe the epidemiology of pickleball foot and ankle injuries including patient demographics, diagnoses, and mechanism of injury. METHODS: A retrospective review from our institutional database identified patients treated in the foot and ankle clinic whose medical records included the search terms "pickleball" and "pickle ball." Only injuries sustained while playing pickleball were included. Patient demographics, diagnosis, mechanism of injury, and treatment were collected. Injury incidence and descriptive analyses were calculated. RESULTS: A total of 198 patients with pickleball foot and ankle injuries were identified. The incidence of injuries increased 6.5-fold from 2019 to 2023. The mean age of patients was 58.3 years (SD = 12.2). Most patients were male (58.6%) and reported a traumatic injury (77.8%). The most common diagnosis was Achilles tendon rupture (39.4%). The most common mechanisms of injury were running or lunging forward (30.9%), planting the foot (16.5%), and inverting the foot and ankle (15.5%). Most injuries were treated nonoperatively (71.2%); however, 62.8% of Achilles tendon ruptures were treated surgically. CONCLUSION: The incidence of pickleball foot and ankle injuries increased dramatically from 2015 to 2023. Injuries occurred more frequently in older, male patients, with Achilles tendon rupture being the most common diagnosis.

Efficiency of Foot and Ankle Surgeries Completed on the Preoperative Stretcher vs Operating Room Table: A Randomized Controlled Trial.

Background: Extremity surgeons frequently operate on the preoperative stretcher rather than the operating room (OR) table. This study sought to identify differences between stretcher-based (SB) and OR table-based (TB) procedures with regard to time efficiency and OR team member preferences. Methods: We conducted a prospective randomized controlled trial comparing the efficiency of SB vs OR TB foot and ankle procedures. Fifty-two patients undergoing a hardware removal, isolated gastrocnemius recession, soft tissue procedure, or foreign body removal at our day surgery unit were included. Start time and exit time were recorded. "Start time" was the number of minutes between the patient entering the OR and first incision. "Exit time" was the number of minutes between the procedure ending and the patient exiting the OR. Surveys were disseminated to OR staff who participated in the included cases. Results: The total measured time in the OR was an average 6 minutes shorter in the Stretcher group compared to the OR Table group (10 minutes vs 16 minutes, P < .001). SB procedures were associated with a significantly shorter start time (median difference = 4 minutes, P = .001), but not exit time (median difference = 1 minute, P = .058). No difference was found in actual surgical time. Thirty (96.8%) OR team members perceived SB procedures as enhancing OR efficiency, and 30 (96.8%) respondents considered SB procedures to be equal or superior to OR TB procedures in terms of patient safety. All would recommend or strongly recommend SB procedures. Conclusion: We found SB foot and ankle procedures to require less room time than OR TB procedures. Particularly for high-volume specialties, an average 6 minutes saved per case may meaningfully improve overall OR efficiency. Most OR team members believed that SB surgery improves OR efficiency and is the safer option for OR team members. Level of Evidence: Level II, randomized controlled trial, survey.

Enter MnIV-NHC: A Dark Photooxidant with a Long-Lived Charge-Transfer Excited State.

Detailed photophysical investigation of a Mn(IV)-carbene complex has revealed that excitation into its lowest-energy absorption band (∼500 nm) results in the formation of an energetic ligand-to-metal charge-transfer (LMCT) state with a lifetime of 15 ns. To the best of our knowledge, this is the longest lifetime reported for charge-transfer states of first-row-based transition metal complexes in solution, barring those based on Cu, with a d10 configuration. A so-called superoxidant, Mn(IV)-carbene exhibits an excited state potential typically only harnessed via excited states of reactive organic radical species. Furthermore, the long-lived excited state in this case is found to be a dark doublet, with its transition to the quartet ground state being spin-forbidden, a contrast to most first-row literature examples, and a possible cause of the long lifetime. Showcasing excited state properties which in some cases exceed those of complexes based on precious metals, these findings not only advance the library of earth-abundant photosensitizers but also shed general insight into the photophysics of d3 and related Mn complexes.

Structure-Based Identification of Novel Histone Deacetylase 4 (HDAC4) Inhibitors.

Histone deacetylases (HDACs) are important cancer drug targets. Existing FDA-approved drugs target the catalytic pocket of HDACs, which is conserved across subfamilies (classes) of HDAC. However, engineering specificity is an important goal. Herein, we use molecular modeling approaches to identify and target potential novel pockets specific to Class IIA HDAC-HDAC4 at the interface between HDAC4 and the transcriptional corepressor component protein NCoR. These pockets were screened using an ensemble docking approach combined with consensus scoring to identify compounds with a different binding mechanism than the currently known HDAC modulators. Binding was compared in experimental assays between HDAC4 and HDAC3, which belong to a different family of HDACs. HDAC4 was significantly inhibited by compound 88402 but not HDAC3. Two other compounds (67436 and 134199) had IC50 values in the low micromolar range for both HDACs, which is comparable to the known inhibitor of HDAC4, SAHA (Vorinostat). However, both of these compounds were significantly weaker inhibitors of HDAC3 than SAHA and thus more selective, albeit to a limited extent. Five compounds exhibited activity on human breast carcinoma and/or urothelial carcinoma cell lines. The present result suggests potential mechanistic and chemical approaches for developing selective HDAC4 modulators.

On the Use and Construction of Wi-Fi Fingerprint Databases for Large-Scale Multi-Building and Multi-Floor Indoor Localization: A Case Study of the UJIIndoorLoc Database.

Large-scale multi-building and multi-floor indoor localization has recently been the focus of intense research in indoor localization based on Wi-Fi fingerprinting. Although significant progress has been made in developing indoor localization algorithms, few studies are dedicated to the critical issues of using existing and constructing new Wi-Fi fingerprint databases, especially for large-scale multi-building and multi-floor indoor localization. In this paper, we first identify the challenges in using and constructing Wi-Fi fingerprint databases for large-scale multi-building and multi-floor indoor localization and then provide our recommendations for those challenges based on a case study of the UJIIndoorLoc database, which is the most popular publicly available Wi-Fi fingerprint multi-building and multi-floor database. Through the case study, we investigate its statistical characteristics with a focus on the three aspects of (1) the properties of detected wireless access points, (2) the number, distribution and quality of labels, and (3) the composition of the database records. We then identify potential issues and ways to address them using the UJIIndoorLoc database. Based on the results from the case study, we not only provide valuable insights on the use of existing databases but also give important directions for the design and construction of new databases for large-scale multi-building and multi-floor indoor localization in the future.

Deep Learning and Neural Architecture Search for Optimizing Binary Neural Network Image Super Resolution.

The evolution of super-resolution (SR) technology has seen significant advancements through the adoption of deep learning methods. However, the deployment of such models by resource-constrained devices necessitates models that not only perform efficiently, but also conserve computational resources. Binary neural networks (BNNs) offer a promising solution by minimizing the data precision to binary levels, thus reducing the computational complexity and memory requirements. However, for BNNs, an effective architecture is essential due to their inherent limitations in representing information. Designing such architectures traditionally requires extensive computational resources and time. With the advancement in neural architecture search (NAS), differentiable NAS has emerged as an attractive solution for efficiently crafting network structures. In this paper, we introduce a novel and efficient binary network search method tailored for image super-resolution tasks. We adapt the search space specifically for super resolution to ensure it is optimally suited for the requirements of such tasks. Furthermore, we incorporate Libra Parameter Binarization (Libra-PB) to maximize information retention during forward propagation. Our experimental results demonstrate that the network structures generated by our method require only a third of the parameters, compared to conventional methods, and yet deliver comparable performance.

Coronary and Cerebrovascular Events and Exacerbation of Existing Conditions After Laboratory-Confirmed Influenza Infection Among US Veterans: A Self-Controlled Case Series Study.

BACKGROUND: Influenza may contribute to coronary/cerebrovascular events and exacerbate underlying conditions. METHODS: We used self-controlled case series (SCCS) design to analyze data from US Veterans ≥18 years with coronary/cerebrovascular or exacerbation event +/-1 year of lab-confirmed influenza (LCI) during 2010-2018. We estimated the incidence ratio (IR) (95% CI) of the event for risk interval (Days 1-7 post-LCI) versus control interval (all other times +/-1 year of LCI) with fixed-effects conditional Poisson regression. We included biomarker data for mediation analysis. RESULTS: We identified 3439 episodes with coronary/cerebrovascular-related hospitalizations. IRs (95% CI) for LCI risk versus control interval were STEMI 0.6 (0.1, 4.4), NSTEMI 7.3 (5.8, 9.2), ischemic stroke 4.0 (3.0, 5.4), hemorrhagic stroke 6.2 (3.4, 11.5), and coronary spasm 1.3 (0.5, 3.0). IR significantly increased for NSTEMI and ischemic stroke among those ≥ 65 years. IR for NSTEMI and ischemic stroke dropped 26% and 10%, respectively, when white blood cell (WBC) and platelet count were considered. LCI was significantly associated with exacerbation of preexisting asthma, chronic obstructive pulmonary disease, and congestive heart failure. CONCLUSIONS: We found significant association between LCI and hospitalization for NSTEMI, ischemic stroke, and hemorrhagic stroke, the latter possibly due to unaccounted time-varying confounding in SCCS design.

High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology.

BACKGROUND: KCNE1 encodes a 129-residue cardiac potassium channel (IKs) subunit. KCNE1 variants are associated with long QT syndrome and atrial fibrillation. However, most variants have insufficient evidence of clinical consequences and thus limited clinical utility. METHODS: In this study, we leveraged the power of variant effect mapping, which couples saturation mutagenesis with high-throughput sequencing, to ascertain the function of thousands of protein-coding KCNE1 variants. RESULTS: We comprehensively assayed KCNE1 variant cell surface expression (2554/2709 possible single-amino-acid variants) and function (2534 variants). Our study identified 470 loss- or partial loss-of-surface expression and 574 loss- or partial loss-of-function variants. Of the 574 loss- or partial loss-of-function variants, 152 (26.5%) had reduced cell surface expression, indicating that most functionally deleterious variants affect channel gating. Nonsense variants at residues 56-104 generally had WT-like trafficking scores but decreased functional scores, indicating that the latter half of the protein is dispensable for protein trafficking but essential for channel function. 22 of the 30 KCNE1 residues (73%) highly intolerant of variation (with > 70% loss-of-function variants) were in predicted close contact with binding partners KCNQ1 or calmodulin. Our functional assay data were consistent with gold standard electrophysiological data (ρ = - 0.64), population and patient cohorts (32/38 presumed benign or pathogenic variants with consistent scores), and computational predictors (ρ = - 0.62). Our data provide moderate-strength evidence for the American College of Medical Genetics/Association of Molecular Pathology functional criteria for benign and pathogenic variants. CONCLUSIONS: Comprehensive variant effect maps of KCNE1 can both provide insight into I Ks channel biology and help reclassify variants of uncertain significance.

Physics-Based Machine Learning Models Predict Carbon Dioxide Solubility in Chemically Reactive Deep Eutectic Solvents.

Carbon dioxide (CO2) is a detrimental greenhouse gas and is the main contributor to global warming. In addressing this environmental challenge, a promising approach emerges through the utilization of deep eutectic solvents (DESs) as an ecofriendly and sustainable medium for effective CO2 capture. Chemically reactive DESs, which form chemical bonds with the CO2, are superior to nonreactive, physically based DESs for CO2 absorption. However, there are no accurate computational models that provide accurate predictions of the CO2 solubility in chemically reactive DESs. Here, we develop machine learning (ML) models to predict the solubility of CO2 in chemically reactive DESs. As training data, we collected 214 data points for the CO2 solubility in 149 different chemically reactive DESs at different temperatures, pressures, and DES molar ratios from published work. The physics-driven input features for the ML models include σ-profile descriptors that quantify the relative probability of a molecular surface segment having a certain screening charge density and were calculated with the first-principle quantum chemical method COSMO-RS. We show here that, although COSMO-RS does not explicitly calculate chemical reaction profiles, the COSMO-RS-derived σ-profile features can be used to predict bond formation. Of the models trained, an artificial neural network (ANN) provides the most accurate CO2 solubility prediction with an average absolute relative deviation of 2.94% on the testing sets. Overall, this work provides ML models that can predict CO2 solubility precisely and thus accelerate the design and application of chemically reactive DESs.

Trimethylsilyldiazomethane Disassembly at a Three-Fold Symmetric Iron Site.

The reaction of equimolar trimethylsilyldiazomethyllithium (LiTMSD) with high spin (S = 2) PhB(AdIm)3FeCl (PhB(AdIm)3- = tris(3-adamantylimidazol-2-ylidene)phenylborate) affords the corresponding N-nitrilimido complex PhB(AdIm)3Fe-N═N═C(SiMe3). This complex can be converted to the thermodynamically more favorable C-isocyanoamido isomer PhB(AdIm)3Fe-C═N═N(SiMe3) by reaction with an additional equivalent of LiTMSD. While the iron(II) complexes are four-coordinate, the diazomethane is bound side-on in the iron(I) congener PhB(AdIm)3Fe(N,N'-κ2-N2C(H)Si(CH3)3). The latter complex adopts high spin (S = 3/2) ground state and features an unusually weak C-H bond. Photolysis of the iron(II) complexes induces N═N bond cleavage, with the iron(II) cyanide PhB(AdIm)3Fe-C≡N and iron(IV) nitride PhB(AdIm)3Fe≡N complexes being the major products of the reaction. The same products are obtained when the iron(I) complex is photolyzed or treated with a fluoride source. The trimethylsilyldiazomethane-derived ligand disassembly reactions are contrasted with those observed for related tris(carbene)amine complexes.

Association of Pharmacologic Treatment of Depression/Anxiety With Initial Patient-Reported Outcome Measures in Patients With Hip and Knee Osteoarthritis.

INTRODUCTION: Depression and anxiety are common comorbidities that may exacerbate osteoarthritis (OA)-related pain. We aim to evaluate the effect of pharmacologic treatment of depression/anxiety on hip and knee patient-reported outcome measures (PROMs). METHODS: A multi-institutional PROMs database was queried for patients with depression or anxiety and hip or knee OA who completed a PROMs questionnaire at an initial orthopaedic visit between January 2015 and March 2023. Data on demographics, comorbidities, and duration of pharmacologic treatment of depression/anxiety were obtained. Patients were stratified into three cohorts based on treatment duration. PROMs were compared across cohorts. RESULTS: Two thousand nine hundred sixty patients who completed PROMs at their initial orthopaedic visit had both OA and depression/anxiety. One hundred thirty-four (4.5%) received pharmacologic treatment of depression/anxiety for < 1 year, versus 196 (6.6%) for more than 1 year. In unadjusted analyses, patients with pharmacologic treatment had significantly lower Patient-Reported Outcomes Measurement Information System (PROMIS)-Physical (39.8 [IQR 34.9, 44.9] vs 42.3 [37.4, 47.7], P < 0.001) and PROMIS-Mental (43.5 [36.3, 50.8] vs 48.3 [41.1, 53.3], P < 0.001) scores than those without treatment. After adjusting for demographics and comorbidities, only differences in PROMIS-Mental scores remained statistically significant, with pharmacologic treatment associated with lower scores (ß = -2.26, 95% CI, [-3.29, -1.24], P < 0.001). On secondary analysis including duration of pharmacologic treatment, < 1 year of treatment was associated with significantly lower PROMIS-Mental scores than those not treated (ß = -4.20, 95% CI [-5.77, -2.62], P < 0.001) while scores of patients with more than 1 year of treatment did not differ significantly from those without treatment. CONCLUSION: :Our results indicate that pharmacologic treatment of depression/anxiety is associated with improved psychological health but not with improved physical symptoms related to OA. We observed a nonsignificant trend that patients with depression/anxiety who warrant pharmacologic treatment tend to have worse physical symptoms than those who do not; however, unadjusted analyses suggest this is a complex relationship beyond the isolated effect of pharmacologic treatment.

Carbon Footprint of Minor Foot and Ankle Surgery: A Randomized Controlled Trial.

Background: Climate change poses a substantial threat to human health, and operating rooms (ORs) have an outsized environmental impact. The Program for Research in Sustainable Medicine (PRiSM) designed a protocol for minor foot and ankle surgery intended to reduce waste, streamline instrument trays, and minimize laundry. We conducted a randomized controlled trial to compare the carbon footprint of procedures performed using the PRiSM protocol vs a traditional protocol. Methods: Forty adult patients undergoing foreign body removal, hammertoe correction, toe amputation, hardware removal, mass excision, or gastrocnemius recession were randomized to the PRiSM or our "Traditional" protocol. The PRiSM protocol used a smaller instrument tray, fewer drapes and towels, and minimal positioning blankets. No changes were made to surgical site preparation or operative techniques. Environmental impact was estimated using the carbon footprint, measured in kilograms of carbon dioxide equivalents (CO2e). Emissions associated with OR waste, instrument processing, and laundry were calculated. Results: On average, PRiSM cases had a smaller carbon footprint than Traditional cases (17.3 kg CO2e [SD = 3.2] vs 20.6 kg CO2e [SD = 2.0], P < .001). Waste-associated emissions from PRiSM cases were reduced (16.0 kg CO2e [SD = 2.7] vs 18.4 kg CO2e [SD = 1.8], P = .002), as were modeled instrument processing-related emissions (0.34 vs 0.91 kg CO2e). One superficial surgical site infection occurred in each group. Conclusion: We found a small but statistically significant reduction in the environmental impact of minor foot and ankle surgery when using the PRiSM vs Traditional protocol. The environmental impact of these cases was dominated by plastic waste-related emissions. Orthopaedic surgeons should think critically about what components of their surgical setup are truly necessary for patient care, as minor changes in product utilization can have significant impacts on waste and greenhouse gas emissions. Level of Evidence: Level I, randomized controlled trial.

Differences in Baseline Physical Function and Mental Health PROM Scores in Patients With Foot and Ankle Conditions.

BACKGROUND: This study sought to establish normative values for baseline physical and mental health by foot and ankle diagnosis using validated PROMIS scores and to compare the correlation between these 2 outcomes across common diagnoses. Additionally, it investigated the effects associated with chronic vs acute conditions and specific diagnoses on mental health. METHODS: We reviewed baseline PROMIS Physical Function 10a (PF10a) and PROMIS Global-Mental (PGM) scores of 14,245 patients with one of the 10 most common foot and ankle diagnoses seen at our institution between 2016 and 2021. Pearson correlation coefficients were calculated to assess the relationship between PF10a and PGM by diagnosis. A multivariable regression model including age, sex, language, race, ethnicity, education level, income, and Charlson Comorbidity Index was used to determine the associated effect of diagnosis on PGM score. RESULTS: On unadjusted analysis, patients diagnosed with an ankle fracture had the lowest mean physical function, whereas patients with hallux valgus had the highest (PF10a = 33.9 vs 46.7, P < .001). Patients with foot/ankle osteoarthritis had the lowest mean self-reported mental health, whereas patients with hallux rigidus had the highest (PGM = 49.9 vs 53.4, P < .001). PF10a and PGM scores were significantly positively correlated for all diagnoses; the correlation was strongest in patients diagnosed with foot/ankle osteoarthritis or hammertoes (r = 0.511) and weakest in patients with ankle fractures (r = 0.232) or sprains (r = 0.280). Chronic conditions, including hammertoes (ß = -5.1, 95% CI [-5.8, -4.3], P < .001), foot/ankle osteoarthritis (ß = -5.0, 95% CI [-5.7, -4.3], P < .001), and hallux valgus (ß = -4.8, 95% CI [-5.5, -4.1], P < .001) were associated with the largest negative effects on patients' mental health. CONCLUSION: Self-reported physical function and mental health varied across common foot and ankle diagnoses and were more tightly correlated in chronic conditions. The associations between diagnosis and mental health scores appear larger for more chronic diagnoses, including those that are generally associated with relatively unimpaired physical function.