Total Synthesis of a Peptide Diatom Sex Pheromone Bearing a Sulfated Aspartic Acid.

The peptide sex-inducing pheromone SIP+ (1) bearing an unusual sulfated aspartic acid residue induces sexual reproduction in diatom populations. Herein, we report the first total synthesis of SIP+ using both a sulfated building block approach and a solid-phase peptide synthesis (SPPS)-compatible late-stage sulfation strategy to assemble the natural product. The modular approaches provide concise routes to useful quantities of the natural product for future structure activity relationship studies examining the role of SIP+ in diatom biology.

A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders.

Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond "total score" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.

Comparison of Patient Health Questionnaire-9, Edinburgh Postnatal Depression Scale and Hospital Anxiety and Depression - Depression subscale scores by administration mode: An individual participant data differential item functioning meta-analysis.

Administration mode of patient-reported outcome measures (PROMs) may influence responses. We assessed if Patient Health Questionnaire-9 (PHQ-9), Edinburgh Postnatal Depression Scale (EPDS) and Hospital Anxiety and Depression Scale - Depression subscale (HADS-D) item responses and scores were associated with administration mode. We compared (1) self-administration versus interview-administration; within self-administration (2) research or medical setting versus private; and (3) pen-and-paper versus electronic; and within interview-administration (4) in-person versus phone. We analysed individual participant data meta-analysis datasets with item-level data for the PHQ-9 (N = 34,529), EPDS (N = 16,813), and HADS-D (N = 16,768). We used multiple indicator multiple cause models to assess differential item functioning (DIF) by administration mode. We found statistically significant DIF for most items on all measures due to large samples, but influence on total scores was negligible. In 10 comparisons conducted across the PHQ-9, EPDS, and HADS-D, Pearson's correlations and intraclass correlation coefficients between latent depression symptom scores from models that did or did not account for DIF were between 0.995 and 1.000. Total PHQ-9, EPDS, and HADS-D scores did not differ materially across administration modes. Researcher and clinicians who evaluate depression symptoms with these questionnaires can select administration methods based on patient preferences, feasibility, or cost.

Latest Advances in Chondrocyte-Based Cartilage Repair.

Chondrocyte-based cell therapy has been used for more than 30 years and is still considered to be a promising method of cartilage repair despite some limitations. This review introduces the latest developments of four generations of autologous chondrocyte implantation and current autologous chondrocyte products. The regeneration of cartilage from adult chondrocytes is limited by culture-induced dedifferentiation and patient age. Cartibeads is an innovative three-step method to produce high-quality hyaline cartilage microtissues, and it is developed from adult dedifferentiated chondrocytes with a high number of cell passages. In addition, allogeneic chondrocyte therapies using the Quantum hollow-fiber bioreactor and several signaling pathways involved in chondrocyte-based cartilage repair are mentioned, such as WNT signaling, the BMP-2/WISP1 pathway, and the FGF19 pathway.

COVID-19 vaccinations and infections among individuals with systemic sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort study.

BACKGROUND/PURPOSE: We previously surveyed adults with systemic sclerosis (SSc) regarding COVID-19 vaccination in April-May 2021. The objective of the present study was to update through June-July 2022 and assess self-reported (1) COVID-19 vaccination rates, including boosters; (2) vaccine-related adverse events; (3) peri­vaccination immunosuppressive medication management; (4) vaccine hesitancy; and (5) prevalence and severity of COVID-19 infections. METHODS: In April-May 2021 and June-July 2022, SPIN Cohort participants completed surveys on COVID-19 vaccination and infection. Primary vaccine series was defined according to the standard for each COVID-19 vaccine; additional vaccine administrations were considered booster doses. Fully vaccinated was defined as having completed a primary vaccine series and at least one booster dose. RESULTS: 544 participants completed the 2021 survey only, 101 the 2022 survey only, and 388 both surveys. Among 489 participants with 2022 data, 437 (89 %) had received both primary and booster vaccines. Among all 1,033 participants, 960 (93 %) received at least one dose. At least one adverse reaction was reported by 34 % (330 of 960 participants) following first, 48 % (314 of 657 participants) following second, and 34 % (147 of 437 participants) following booster vaccine doses (primarily sore arm and fatigue); no severe adverse reactions were reported. SSc symptom worsening was reported in 6 % (53 of 960) after the first, 6 % after the second (39 of 657), and 4 % (17 of 437) after the booster dose. Of participants taking methotrexate or mycophenolate (including Cellcept or Myfortic), 34 of 266 (13 %) reported that they temporarily stopped or decreased their medication at the first dose, 32 of 215 (15 %) at the second dose, and 28 of 148 (19 %) for booster vaccination. Of 52 individuals not fully vaccinated with primary and booster doses in 2022, 29 (56 %) reported worry about vaccine related SSc flares. 172 of 489 (35 %) 2022 participants reported a history of at least one COVID-19 infection; 114 (66 %) occurred after receiving at least a primary vaccine series. Among initial COVID-19 infections, 9 (5 %) were asymptomatic, 66 (38 %) involved mild symptoms, 82 (48 %) moderate symptoms, and 15 (9 %) required hospitalization. CONCLUSION: Most people with SSc in the study were fully vaccinated, and most continued their methotrexate or mycophenolate post-primary and booster vaccinations. Over half of vaccine-hesitant participants were concerned regarding risk of SSc flare; however, few vaccinated participants reported this. These data may be useful for counselling people with SSc regarding COVID-19 vaccine safety and outcomes.

Assembly of a trapped valent CeIII/IV-TCNQ complex through metal-ligand redox cooperativity.

Complex (Cp3CeIV)2(TCNQ)(CeIIICp3)2 (1) was prepared by reducing neutral TCNQ0 (tetracyanoquinodimethane) with Cp3Ce(THF). Two types of cerium centres with a dianionic TCNQ2- moiety are present in 1, wherein each of the four cyano-groups are bound by a cation. Formation of this trapped-valent organocerium compound 1 is facilitated by metal-ligand redox cooperativity. Characterization of 1 was carried out using structural-, magnetometry-, and IR-spectroscopic analyses. Photophysical studies on this compound reveal CeIII luminescence, and opens up avenues for promising multifunctional, mixed-valent lanthanide materials.

Two germ granule eIF4E isoforms reside in different mRNPs to hand off C elegans mRNAs from translational repression to activation.

We studied the function of translation factor eIF4E isoforms in regulating mRNAs in germ cell granules/condensates. Translational control of mRNAs plays an essential role in germ cell gene regulation. Messenger ribonucleoprotein (mRNP) complexes assemble on mRNAs as they move from the nucleus into perinuclear germ granules to exert both positive and negative post-transcriptional regulation in the cytoplasm. In C. elegans , germ granules are surprisingly dynamic mRNP condensates that remodel during development. Two eIF4E isoforms (called IFE-1 and IFE-3), eIF4E-Interacting Proteins (4EIPs), RBPs, DEAD-box helicases, polyadenylated mRNAs, Argonautes and miRNAs all occupy positions in germ granules. Affinity purification of IFE-1 and IFE-3 allowed mass spectrometry and mRNA-Seq to identify the proteins and mRNAs that populate stable eIF4E mRNPs. We find translationally controlled mRNAs (e.g. pos-1, mex-3, spn-4, etc.) enriched in IFE-3 mRNPs, but excluded from IFE-1 mRNPs. These mRNAs also require IFE-1 for efficient translation. The findings support a model in which oocytes and embryos utilize the two eIF4Es for opposite purposes on critically regulated germline mRNAs. Careful colocalization of the eIF4Es with other germ granule components suggests an architecture in which GLH-1, PGL-1 and the IFEs are stratified to facilitate sequential interactions for mRNAs. Biochemical characterization demonstrates opposing yet cooperative roles for IFE-3 and IFE-1 to hand-off of translationally controlled mRNAs from the repressed to the activated state, respectively. The model involves eIF4E mRNPs shuttling mRNAs through nuclear pore-associated granules/condensates to cytoplasmic ribosomes.

Protocol for the development of a tool to map systemic sclerosis pain sources, patterns, and management experiences: a Scleroderma Patient-centered Intervention Network patient-researcher partnership.

INTRODUCTION: Systemic sclerosis (SSc) is a rare, complex autoimmune rheumatic disease with multiple factors that contribute to pain. People with SSc emphasize the effect pain has on their quality of life, but no studies have systematically examined the frequency and relative importance of different SSc pain sources, patterns of pain from different sources, and pain management experiences. Our objectives are to (1) develop a tool, jointly with researchers, health care providers, and patients, to map sources of pain in SSc, determine patterns of pain from different sources, and understand pain management experiences; and (2) administer the final tool version to participants in the large multinational Scleroderma Patient-centered Intervention Network (SPIN) Cohort. METHODS: First, we will use validated pain assessment tools as templates to develop an initial version of our pain assessment tool, and we will obtain input from patient advisors to adapt it for SSc. The tool will include questions on pain sources, pain patterns, pain intensity, pain management techniques, and barriers to pain management in SSc. Second, we will conduct nominal group technique sessions with people living with SSc and health care providers who care for people with SSc to further refine the tool. Third, we will conduct individual usability testing sessions with SPIN Cohort participants. Once the tool has been finalized, we will administer it to individuals in the multinational SPIN Cohort, which currently includes over 1,300 active participants from 54 sites in 7 countries. We will perform unsupervised clustering using the KAy-Means for MIxed LArge data (KAMILA) method to identify participant subgroups with similar profiles of pain sources (present or absent) and to evaluate predictors of subgroup membership. We will use latent profile analysis to identify subgroups of participants with similar profiles based on pain intensity scores for each pain source and evaluate predictors. DISCUSSION: Once completed, our pain assessment tool will allow our team and other researchers to map sources of pain in SSc and to understand pain management experiences of people living with SSc. This knowledge will provide avenues for studies on the pathophysiology of pain in SSc and studies of interventions to improve pain management.

Outcomes of Arthroscopic Stabilization for Posterior Shoulder Instability - A Systematic Review.

BACKGROUND: Posterior shoulder instability makes up approximately 10% of all shoulder instability cases and its diagnosis and treatment is less well understood. Recently, however, there has been increased recognition of posterior instability and posterior stabilization. The purpose of this study was to systematically review the literature to ascertain the outcomes on arthroscopic stabilization of posterior shoulder instability. METHODS: Two independent reviewers conducted a systematic literature search based on PRISMA guidelines, utilizing the MEDLINE database. Studies were eligible for inclusion if they reported postoperative outcomes for posterior shoulder instability following arthroscopic stabilization. RESULTS: A total of 48 studies met inclusion criteria for review including 2307 shoulders. Majority of patients were male (83.3%), with an average age of 26.1 years and a mean follow-up of 46.8 months. The functional outcome score primarily utilized for postoperative assessment was ASES with an average of 84.77. Overall, 90.9% of patients reported being satisfied with their arthroscopic stabilization. Recurrent instability occurred in 7.4% of patients. The total revision rate was 5.2%. 16.6% of patients reported residual pain postoperatively. The rate of return to play was 86.4% with 68.0% of patients returning to play at the same or higher level of play. CONCLUSION: Arthroscopic stabilization of posterior shoulder instability resulted in good outcomes with high patient satisfaction and low rates of recurrent instability, revisions, and residual pain.

Physical activity during COVID-19 in people with systemic sclerosis: A Scleroderma Patient-centred Intervention Network COVID-19 Cohort longitudinal study.

Introduction/Objective: People with systemic sclerosis (SSc) face barriers to physical activity. Few studies have described physical activity in SSc, and none have explored physical activity longitudinally during COVID-19. We evaluated physical activity from April 2020 to March 2022 among people with SSc. Methods: The Scleroderma Patient-centred Intervention Network (SPIN) COVID-19 Cohort was launched in April 2020 and included participants from the ongoing SPIN Cohort plus external enrolees. Participants completed measures bi-weekly through July 2020, then every 4 weeks afterwards (28 assessments). Physical activity was assessed via the self-reported International Physical Activity Questionnaire-Elderly. Analyses included estimated means with 95% confidence intervals for physical activity across assessments. Missing data were imputed for main analyses. Sensitivity analyses included evaluating only participants who completed >90% of items for >21 of 28 possible assessments ('completers') and stratified analyses by sex, age, country and SSc subtype. Results: A total of 800 people with SSc enrolled. Mean age was 55.6 (standard deviation (SD) = 12.6) years. Physical activity significantly decreased from April 2020 to March 2021 (standardized mean difference (SMD) = -0.17, 95% confidence interval (CI) = -0.26 to -0.07) and was stable from March 2021 to March 2022 (SMD = -0.05, 95% CI = -0.15 to 0.05). Results were similar for completers and subgroups. The proportion of participants who met World Health Organization minimum physical activity recommendations of at least 150 min of moderate-to-vigorous activity per week ranged from 63% to 82% across assessments. Conclusion: Physical activity decreased by a relatively small amount, on average, across the pandemic. Most participants met recommended physical activity levels.

Minimal Detectable Changes of the HAQ-DI, PROMIS-29v2.0 Domains, and PHQ-8 in Systemic Sclerosis: A SPIN Cohort Cross-Sectional Study.

OBJECTIVE: Systemic sclerosis (SSc) is a rare, chronic, autoimmune disorder associated with disability, diminished physical function, fatigue, pain, and mental health concerns. We assessed minimal detectable changes (MDCs) of the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient Reported Outcomes Measurement Information System-29 Profile version 2.0 (PROMIS-29v2.0) domains, and Patient Health Questionnaire-8 (PHQ-8) in SSc. METHODS: Scleroderma Patient-centered Intervention Network Cohort participants completed the HAQ-DI, PROMIS-29v2.0 domains, and PHQ-8 at baseline assessments from April 2014 until August 2023. We estimated MDC95 and MDC90 with 95% confidence intervals (CI) generated via the percentile bootstrapping method resampling 1000 times. We compared MDC estimates by age, sex and SSc subtype. RESULTS: A total of 2,571 participants were included. Most were female (N = 2,241; 87%), and 38% (N = 976) had diffuse SSc. Mean (SD) age was 54.9 (12.7) years and duration since onset of first non-Raynaud phenomenon symptom 10.8 (8.7) years. MDC95 estimate was 0.41 points (95% CI: 0.40 to 0.42) for the HAQ-DI, between 4.88 points (95% CI: 4.72 to 5.05) and 9.02 points (95% CI: 8.80 to 9.23) for the 7 PROMIS-29v2.0 domains, and 5.16 points (95% CI: 5.06 to 5.26) for the PHQ-8. MDC95 estimates were not materially different across subgroups. CONCLUSION: MDC95 and MDC90 estimates were precise and similar across age, sex and SSc subtype groups. HAQ-DI MDC95 and MDC90 were substantially larger than previous estimates of HAQ-DI minimal important difference from several small studies. Minimally important differences of all measures should be evaluated in large studies using anchor-based methods.

Association of COVID-19 vaccination and anxiety symptoms: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort longitudinal study.

OBJECTIVE: Symptoms of anxiety increased early in the COVID-19 pandemic among people with systemic sclerosis (SSc) then returned to pre-pandemic levels, but this was an aggregate finding and did not evaluate whether vaccination may have contributed to reduced anxiety symptom levels. We investigated whether being vaccinated for COVID-19 was associated with reduced anxiety symptoms among people with SSc. METHODS: The longitudinal Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 Cohort was launched in April 2020 and included participants from the ongoing SPIN Cohort and external enrollees. Participants completed measures bi-weekly through July 2020, then every 4 weeks afterwards through August 2022 (32 assessments). We used linear mixed models to evaluate longitudinal trends of PROMIS Anxiety 4a v1.0 anxiety domain scores and their association with vaccination. RESULTS: Among 517 participants included in analyses, 489 (95%) were vaccinated by September 2021, and no participants were vaccinated subsequently. Except for briefly at the beginning, when few had received a vaccine, and end, when only 28 participants remained unvaccinated, anxiety symptom trajectories were largely overlapping. Participants who were never vaccinated had higher anxiety symptoms by August 2022, but there were no other differences, and receiving a vaccination did not appear to change anxiety symptom trajectories meaningfully. CONCLUSION: Vaccination did not appear to influence changes in anxiety symptoms among vulnerable people with SSc during the COVID-19 pandemic. This may be due to people restricting their behavior when they were unvaccinated and returning to more normal social engagement once vaccinated to maintain a steady level of anxiety symptoms.

Individual Patient Data Meta-Analysis Estimates the Minimal Detectable Change of the Geriatric Depression Scale-15.

OBJECTIVE: To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine whether MDC may differ based on participant characteristics and study-level variables. STUDY DESIGN AND SETTING: This was a secondary analysis of data from an IPDMA on the depression screening accuracy of the GDS. Datasets from studies published in any language were eligible for the present study if they included GDS-15 scores for participants aged 60 or older. MDC of the GDS-15 was estimated via random-effects meta-analysis using 2.77 (MDC95) and 1.41 (MDC67) standard errors of measurement (SEM). Subgroup analyses were used to evaluate differences in MDC by participant age and sex. Meta-regression was conducted to assess for differences based on study-level variables, including mean age, proportion male, proportion with major depression, and recruitment setting. RESULTS: 5,876 participants (mean age 76 years, 40% male, 11% with major depression) from 21 studies were included. The MDC95 was 3.81 points (95% confidence interval [CI] 3.59, 4.04), and MDC67 was 1.95 (95% CI 1.83, 2.03). The difference in MDC95 was 0.26 points (95% CI 0.04, 0.48) between ≥ 80-year-olds and < 80-year-olds; MDC95 was similar for females and males (0.05, 95% CI -0.12, 0.22). The MDC95 increased by 0.29 points (95% CI 0.17, 0.41) per 10% increase in proportion of participants with major depression; mean age had a small association (0.04 points, 95% CI 0.00 to 0.09) with MDC95, but sex and recruitment setting were not significantly associated. CONCLUSIONS: The MDC95 was 3.81 points and MDC67 was 1.95 points. MDC95 increased with the proportion of participants with major depression. Results can be used to evaluate individual changes in depression symptoms and as a threshold for assessing minimal clinical important difference estimates.

iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection.

Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult. We have developed a new analytical approach, in silico gating annotating training elucidating (iGATE), based on probabilistic support vector machine classification. By rapidly and accurately "gating" tens of millions of cells in silico into user-defined types, iGATE enabled us to track 25 canonical immune cell types in mouse lung over the course of influenza infection. Applying iGATE to study effects of host genetic background, we show that the lower survival of C57BL/6 mice compared with BALB/c was associated with a more rapid accumulation of inflammatory cell types and decreased IL-10 expression. Furthermore, we demonstrate that the most prominent effect of aging is a defective T cell response, reducing survival of aged mice. Finally, iGATE reveals that the 25 canonical immune cell types exhibited differential influenza infection susceptibility and replication permissiveness in vivo, but neither property varied with host genotype or aging. The software is available at https://github.com/UmichWenLab/iGATE.

Kartogenin Induces Chondrogenesis in Cartilage Progenitor Cells and Attenuates Cell Hypertrophy in Marrow-Derived Stromal Cells.

INTRODUCTION: Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor ß, which remain under strict regulatory scrutiny when it comes to use in patients. METHOD: This study reports the previously unexplored effects of KGN stimulation on cartilage- derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration. Our findings demonstrate that KGN treatment significantly increased markers of chondrogenesis, SOX9 and COL2 following 3-10 days of treatment in human CPCs. RESULT: KGN treatment also resulted in a significant dose-dependent increase in GAG production in CPCs. The same efficacy was not observed in human marrow-derived stromal cells (BM-MSCs); however, KGN significantly reduced mRNA expression of cell hypertrophy markers, COL10 and MMP13, in BM-MSCs. Parallel to these mRNA expression results, KGN led to a significant decrease in protein levels of MMP-13 both at 0-5 days and 5-10 days following KGN treatment. CONCLUSION: In conclusion, this study demonstrates that KGN can boost the chondrogenicity of CPCs and inhibit hypertrophic terminal differentiation of BM-MSCs.

An ALK2 inhibitor, BLU-782, prevents heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease driven by gain-of-function variants in activin receptor-like kinase 2 (ALK2), the most common variant being ALK2R206H. In FOP, ALK2 variants display increased and dysregulated signaling through the bone morphogenetic protein (BMP) pathway resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of BLU-782 (IPN60130), a small-molecule ALK2R206H inhibitor developed for the treatment of FOP. A small-molecule library was screened in a biochemical ALK2 binding assay to identify potent ALK2 binding compounds. Iterative rounds of structure-guided drug design were used to optimize compounds for ALK2R206H binding, ALK2 selectivity, and other desirable pharmacokinetic properties. BLU-782 preferentially bound to ALK2R206H with high affinity, inhibiting signaling from ALK2R206H and other rare FOP variants in cells in vitro without affecting signaling of closely related homologs ALK1, ALK3, and ALK6. In vivo efficacy of BLU-782 was demonstrated using a conditional knock-in ALK2R206H mouse model, where prophylactic oral dosing reduced edema and prevented cartilage and heterotopic ossification (HO) in both muscle and bone injury models. BLU-782 treatment preserved the normal muscle-healing response in ALK2R206H mice. Delayed dosing revealed a short 2-day window after injury when BLU-782 treatment prevented HO in ALK2R206H mice, but dosing delays of 4 days or longer abrogated HO prevention. Together, these data suggest that BLU-782 may be a candidate for prevention of HO in FOP.

Influence of Isolated Talonavicular and Subtalar Joint Arthrodesis on Hindfoot Kinematics and Range of Motion During Cadaveric Gait Simulation.

BACKGROUND: Isolated subtalar and talonavicular joint arthrodeses have been associated with adjacent joint arthritis and altered hindfoot kinematics during simplified loading scenarios. However, the effect on kinematics during dynamic activity is unknown. This study assessed changes in subtalar and talonavicular kinematics after isolated talonavicular (TNiso) and subtalar (STiso) arthrodesis, respectively, during stance simulations. METHODS: Fourteen midtibia specimens received either a TNiso or STiso arthrodesis, with 7 randomized to each group. A 6-degree-of-freedom robot sequentially simulated the stance phase for the intact and arthrodesis conditions. Bootstrapped bias-corrected 95% CIs of the talonavicular and subtalar joint kinematics were calculated and compared between conditions. RESULTS: The TNiso decreased subtalar inversion, adduction, and plantarflexion in late stance (P < .05). The subtalar range of motion in the sagittal and coronal planes decreased by 40% (P = .009) and 46% (P = .002), respectively. No significant changes in talonavicular joint kinematics were observed after isolated subtalar arthrodesis; however, the range of motion was reduced by 61% (P = .007) and 50% (P = .003) in the coronal and axial planes, respectively. CONCLUSION: In this model for arthrodesis, changes in subtalar kinematics and motion restriction were observed after isolated talonavicular arthrodesis, and motion restriction was observed after isolated subtalar arthrodesis. Surprisingly, talonavicular kinematics did not appear to change after isolated subtalar arthrodesis. CLINICAL RELEVANCE: Both joint fusions substantially decrease the motion of the reciprocal adjacent joint. Surgeons should be aware that the collateral costs with talonavicular fusion appear higher, and it has a significant effect on subtalar kinematics during the toe-off phase of gait.