Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate.

Metazoan evolution involves increasing protein domain complexity, but how this relates to control of biological decisions remains uncertain. The Ras guanine nucleotide exchange factor (RasGEF) Sos1 and its adaptor Grb2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the Ras-Erk pathway during mammalian development and drive embryonic stem cells toward the primitive endoderm (PrE) lineage. We show that the ability of Sos1/Grb2 to appropriately regulate pluripotency and differentiation factors and to initiate PrE development requires collective binding of multiple Sos1/Grb2 domains to their protein and phospholipid ligands. This provides a cooperative system that only allows lineage commitment when all ligand-binding domains are occupied. Furthermore, our results indicate that the interaction domains of Sos1 and Grb2 have evolved so as to bind ligands not with maximal strength but with specificities and affinities that maintain cooperativity. This optimized system ensures that PrE lineage commitment occurs in a timely and selective manner during embryogenesis.

Mapping the global interactome of the ARF family reveals spatial organization in cellular signaling pathways.

The ADP-ribosylation factors (ARFs) and ARF-like (ARL) GTPases serve as essential molecular switches governing a wide array of cellular processes. In this study, we used proximity-dependent biotin identification (BioID) to comprehensively map the interactome of 28 out of 29 ARF and ARL proteins in two cellular models. Through this approach, we identified ∼3000 high-confidence proximal interactors, enabling us to assign subcellular localizations to the family members. Notably, we uncovered previously undefined localizations for ARL4D and ARL10. Clustering analyses further exposed the distinctiveness of the interactors identified with these two GTPases. We also reveal that the expression of the understudied member ARL14 is confined to the stomach and intestines. We identified phospholipase D1 (PLD1) and the ESCPE-1 complex, more precisely, SNX1, as proximity interactors. Functional assays demonstrated that ARL14 can activate PLD1 in cellulo and is involved in cargo trafficking via the ESCPE-1 complex. Overall, the BioID data generated in this study provide a valuable resource for dissecting the complexities of ARF and ARL spatial organization and signaling.

Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP.

RAS GTPases bind effectors to convert upstream cues to changes in cellular function. Effectors of classical H/K/NRAS are defined by RBD/RA domains which recognize the GTP-bound conformation of these GTPases, yet the specificity of RBD/RAs for over 160 RAS superfamily proteins remains poorly explored. We have systematically mapped interactions between BRAF and four RASSF effectors, the largest family of RA-containing proteins, with all RAS, RHO and ARF small GTPases. 39 validated complexes reveal plasticity in RASSF binding, while BRAF demonstrates tight specificity for classical H/K/NRAS. Complex between RASSF5 and diverse RAS GTPases at the plasma membrane can activate Hippo signalling and sequester YAP in the cytosol. RASSF8 undergoes liquid-liquid phase separation and resides in YAP-associated membraneless condensates, which also engage several RAS and RHO GTPases. The poorly studied RASSF3 has been identified as a first potential effector of mitochondrial MIRO proteins, and its co-expression with these GTPases impacts mitochondria and peroxisome distribution. These data reveal the complex nature of GTPase-effector interactions and show their systematic elucidation can reveal completely novel and biologically relevant cellular processes.

Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion.

The association of p120 catenin (p120) with the juxtamembrane domain (JMD) of the cadherin cytoplasmic tail is critical for the surface stability of cadherin-catenin cell-cell adhesion complexes. Here, we present the crystal structure of p120 isoform 4A in complex with the JMD core region (JMD(core)) of E-cadherin. The p120 armadillo repeat domain contains modular binding pockets that are complementary to electrostatic and hydrophobic properties of the JMD(core). Single-residue mutations within the JMD(core)-binding site of p120 abolished its interaction with E- and N-cadherins in vitro and in cultured cells. These mutations of p120 enabled us to clearly differentiate between N-cadherin-dependent and -independent steps of neuronal dendritic spine morphogenesis crucial for synapse development. NMR studies revealed that p120 regulates the stability of cadherin-mediated cell-cell adhesion by associating with the majority of the JMD, including residues implicated in clathrin-mediated endocytosis and Hakai-dependent ubiquitination of E-cadherin, through its discrete "dynamic" and "static" binding sites.

Defining bone fide effectors of RAS GTPases.

RAS GTPases play essential roles in normal development and are direct drivers of human cancers. Three decades of study have failed to wholly characterize pathways stimulated by activated RAS, driven by engagement with 'effector' proteins that have RAS binding domains (RBDs). Bone fide effectors must bind directly to RAS GTPases in a nucleotide-dependent manner, and this interaction must impart a clear change in effector activity. Despite this, for most proteins currently deemed effectors there is little mechanistic understanding of how binding to the GTPase alters protein function. There has also been limited effort to comprehensively resolve the specificity of effector binding to the full array of RAS superfamily GTPase proteins. This review will summarize what is known about RAS-driven activation for an array of potential effector proteins, focusing on structural and mechanistic effects and highlighting how little is still known regarding this key paradigm of cellular signal transduction.

MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.

BACKGROUND: Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated. OBJECTIVES: This study sought to determine the activity of MYSM1 in regulating DNA damage responses (DDRs) to DNA double-stranded breaks (DSBs) generated during immunoglobulin receptor gene (Ig) recombination and by ionizing radiation. METHODS: MYSM1-deficient pre- and non-B cells were used to determine the role of MYSM1 in DSB generation, DSB repair, and termination of DDRs. RESULTS: Genetic testing in a newborn with abnormal screen for severe combined immune deficiency, T-cell lymphopenia, and near absence of B cells identified a novel splice variant in MYSM1 that results in nearly absent protein expression. Radiosensitivity testing in patient's peripheral blood lymphocytes showed constitutive γH2AX, a marker of DNA damage, in B cells in the absence of irradiation, suggesting a role for MYSM1 in response to DSBs generated during Ig recombination. Suppression of MYSM1 in pre-B cells did not alter generation or repair of Ig DSBs. Rather, loss of MYSM1 resulted in persistent DNA damage foci and prolonged DDR signaling. Loss of MYSM1 also led to protracted DDRs in U2OS cells with irradiation induced DSBs. CONCLUSIONS: MYSM1 regulates termination of DNA damage responses but does not function in DNA break generation and repair.

Mapping the MOB proteins' proximity network reveals a unique interaction between human MOB3C and the RNase P complex.

Distinct functions mediated by members of the monopolar spindle-one-binder (MOB) family of proteins remain elusive beyond the evolutionarily conserved and well-established roles of MOB1 (MOB1A/B) in regulating tissue homeostasis within the Hippo pathway. Since MOB proteins are adaptors, understanding how they engage in protein-protein interactions and help assemble complexes is essential to define the full scope of their biological functions. To address this, we undertook a proximity-dependent biotin identification approach to define the interactomes of all seven human MOB proteins in HeLa and human embryonic kidney 293 cell lines. We uncovered >200 interactions, of which at least 70% are unreported on BioGrid. The generated dataset reliably recalled the bona fide interactors of the well-studied MOBs. We further defined the common and differential interactome between different MOBs on a subfamily and an individual level. We discovered a unique association between MOB3C and 7 of 10 protein subunits of the RNase P complex, an endonuclease that catalyzes tRNA 5' maturation. As a proof of principle for the robustness of the generated dataset, we validated the specific interaction of MOB3C with catalytically active RNase P by using affinity purification-mass spectrometry and pre-tRNA cleavage assays of MOB3C pulldowns. In summary, our data provide novel insights into the biology of MOB proteins and reveal the first interactors of MOB3C, components of the RNase P complex, and hence an exciting nexus with RNA biology.

Development of a Desorption Electrospray Ionization-Multiple-Reaction-Monitoring Mass Spectrometry (DESI-MRM) Workflow for Spatially Mapping Oxylipins in Pulmonary Tissue.

Oxylipins are a class of low-abundance lipids formed via oxygenation of fatty acids. These compounds include potent signaling molecules (e.g., octadecanoids, eicosanoids) that can exert essential functions in the pathophysiology of inflammatory diseases including asthma. While some oxylipin signaling cascades have been unraveled using LC-MS/MS-based methods, measurements in homogenate samples do not represent the spatial heterogeneity of lipid metabolism. Mass spectrometry imaging (MSI) directly detects analytes from a surface, which enables spatial mapping of oxylipin biosynthesis and migration within the tissue. MSI has lacked the sensitivity to routinely detect low-abundance oxylipins; however, new multiple-reaction-monitoring (MRM)-based MSI technologies show increased sensitivity. In this study, we developed a workflow to apply desorption electrospray ionization coupled to a triple quadrupole mass spectrometer (DESI-MRM) to spatially map oxylipins in pulmonary tissue. The targeted MSI workflow screened guinea pig lung extracts using LC-MS/MS to filter oxylipin targets based on their detectability by DESI-MRM. A panel of 5 oxylipins was then selected for DESI-MRM imaging derived from arachidonic acid (TXB2, 11-HETE, 12-HETE), linoleic acid (12,13-DiHOME), and α-linolenic acid (16-HOTrE). To parse this new data type, a custom-built R package (quantMSImageR) was developed with functionality to label regions of interest as well as quantify and analyze lipid distributions. The spatial distributions quantified by DESI-MRM were supported by LC-MS/MS analysis, with both indicating that 16-HOTrE and 12-HETE were associated with airways, while 12,13-DiHOME and arachidonic acid were mapped to parenchyma. This study realizes the potential of targeted MSI to routinely map low-abundance oxylipins with high specificity at scale.

Interactions between zinc and NRF2 in vascular redox signalling.

Recent evidence highlights the importance of trace metal micronutrients such as zinc (Zn) in coronary and vascular diseases. Zn2+ plays a signalling role in modulating endothelial nitric oxide synthase and protects the endothelium against oxidative stress by up-regulation of glutathione synthesis. Excessive accumulation of Zn2+ in endothelial cells leads to apoptotic cell death resulting from dysregulation of glutathione and mitochondrial ATP synthesis, whereas zinc deficiency induces an inflammatory phenotype, associated with increased monocyte adhesion. Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor known to target hundreds of different genes. Activation of NRF2 affects redox metabolism, autophagy, cell proliferation, remodelling of the extracellular matrix and wound healing. As a redox-inert metal ion, Zn has emerged as a biomarker in diagnosis and as a therapeutic approach for oxidative-related diseases due to its close link to NRF2 signalling. In non-vascular cell types, Zn has been shown to modify conformations of the NRF2 negative regulators Kelch-like ECH-associated Protein 1 (KEAP1) and glycogen synthase kinase 3ß (GSK3ß) and to promote degradation of BACH1, a transcriptional suppressor of select NRF2 genes. Zn can affect phosphorylation signalling, including mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinases and protein kinase C, which facilitate NRF2 phosphorylation and nuclear translocation. Notably, several NRF2-targeted proteins have been suggested to modify cellular Zn concentration via Zn exporters (ZnTs) and importers (ZIPs) and the Zn buffering protein metallothionein. This review summarises the cross-talk between reactive oxygen species, Zn and NRF2 in antioxidant responses of vascular cells against oxidative stress and hypoxia/reoxygenation.

Effect of making skin incision with electrocautery on positive Cutibacterium acnes culture rates in shoulder arthroplasty: a prospective randomized clinical trial.

BACKGROUND: Cutibacterium acnes remains the most commonly detected organism in shoulder arthroplasty. C acnes infection is thought to occur during shoulder arthroplasty through contamination of the surgical field with C acnes from the incised dermis. The purpose of this study was to examine whether using electrocautery for making skin incisions would decrease C acnes culture rates at the incised dermis compared to using scalpels during shoulder arthroplasty. METHODS: Patients undergoing primary shoulder arthroplasty were randomized into 2 groups, electrocautery vs. scalpel incision group. All patients received a standard preoperative antiseptic preparation including chlorhexidine gluconate showers, intravenous antibiotic administration, and topical application of hydrogen peroxide, povidone iodine, isopropyl alcohol, and DuraPrep. Cultures were obtained from the incised dermal edge immediately after skin incision and later from surgeon's gloves and forceps immediately prior to humeral component implantation. The primary outcome was positive C acnes culture rates compared between the groups. RESULTS: A total of 64 patients (32 in each group) were enrolled. There were 24 males in each group. Regarding dermis cultures, 10 patients (31%) in the scalpel group were positive with 8 of them positive for C acnes, whereas no patients in the electrocautery group were positive (P < .001). Regarding glove cultures, the electrocautery group had 8 patients positive C acnes, while the scalpel group had 8 (P = .777). Regarding forceps cultures, the electrocautery group had 4 patients positive for C acnes, and the scalpel group had 6 (P = .491). All positive cultures were exclusively from male patients. There were no wound complications or infection in the electrocautery group while the scalpel group had 1 acute postoperative infection. CONCLUSIONS: Making skin incisions using electrocautery resulted in 0 C acnes culture at the incised dermis, suggesting its potential effect against C acnes. However, despite this initial antibacterial effect, C acnes still appeared on surgeon's gloves and forceps during surgery of male patients. All positive cultures were from male patients, suggesting that the source of C acnes was specifically related to the male body. While the study hypothesis was supported by the results, the present study also raises new questions and calls for further research.

Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.

Modular baseplate augmentation: a simple and effective method for addressing eccentric glenoid wear.

BACKGROUND: Augmented baseplates can be effective at addressing eccentric glenoid wear in reverse total shoulder arthroplasty. However, these implants often come in a limited number of predetermined shapes that require additional reaming to ensure adequate glenoid seating. This typically involves complex instrumentation and can have a negative impact on implant stability. Modular baseplate augmentation based on intraoperative measurements may allow for more precise defect filling while preserving glenoid bone. The purpose of this investigation was to assess the stability of a novel ringed baseplate with modular augmentation in comparison with nonaugmented standard and ringed baseplate designs. METHODS: In this biomechanical study, baseplate micromotion was tested for 3 constructs according to the American Society for Testing and Materials guidelines. The constructs included a nonaugmented curved baseplate, a nonaugmented ringed baseplate, and a ringed baseplate with an 8-mm locking modular augmentation peg. The nonaugmented constructs were mounted flush onto polyurethane foam blocks, whereas the augmented baseplate was mounted on a polyurethane block with a simulated defect. Baseplate displacement was measured before and after 100,000 cycles of cyclic loading. RESULTS: Before cyclic loading, the nonaugmented and augmented ringed baseplates both demonstrated significantly less micromotion than the nonaugmented curved baseplate design (81.1 µm vs. 97.2 µm vs. 152.7 µm; P = .009). After cyclic loading, both ringed constructs continued to have significantly less micromotion than the curved design (105.5 µm vs. 103.2 µm vs. 136.6 µm; P < .001). The micromotion for both ringed constructs remained below the minimum threshold required for bony ingrowth (150 µm) at all time points. CONCLUSIONS: In the setting of a simulated glenoid defect, locked modular augmentation of a ringed baseplate does not result in increased baseplate micromotion when compared with full contact nonaugmented baseplates. This design offers a simple method for tailored baseplate augmentation that can match specific variations in glenoid anatomy, limiting the need for excessive reaming and ultimately optimizing the environment for long-term implant stability.

Computerized Suicide Prevention Clinical Training Simulations: A Pilot Study.

Purpose: Mental health providers are well-positioned to engage in suicide prevention efforts, yet implementation depends on skill acquisition and providers often report feeling underprepared. This pilot study explored the acceptability, feasibility, and preliminary effectiveness of three suicide prevention-focused simulations with virtual clients. Method: Students (n=22) were recruited from a MSW program, completed pre- and post-test surveys, and engaged with three simulated trainings: 1) suicide risk assessment, 2) safety planning, and 3) motivating a client to treatment. Results: Simulations were reported to be acceptable and feasible, with strong student desire and need for greater suicide prevention training. We observed significant improvements over time in clinical skills via simulated training scores and perceptions of clinical preparedness. Discussion: Preliminary findings indicate simulated training with virtual clients is promising and suggest the three suicide prevention simulations may be useful, scalable, and effective in social work training programs and beyond.

The Need for Technology-Aided Instruction and Intervention Policy for Autistic Youth.

This paper examines current technology-aided instruction and intervention (TAII) available for autistic transition-age youth (TAY) and existing policies that may support or hinder the delivery of these interventions. Specifically, we focus on policies that might influence the delivery of TAII to autistic TAY. After a careful review of the literature, we observed that postsecondary policy guiding the delivery of TAII designed to support autistic TAY is lacking. TAII have demonstrated effectiveness, usability, sustainability, and cost-effectiveness, particularly with this population. We suggest possibilities for future policies to support the development, implementation, and evaluation of TAII for autistic TAY.

Higher-order interactions stabilize dynamics in competitive network models.

Ecologists have long sought a way to explain how the remarkable biodiversity observed in nature is maintained. On the one hand, simple models of interacting competitors cannot produce the stable persistence of very large ecological communities. On the other hand, neutral models, in which species do not interact and diversity is maintained by immigration and speciation, yield unrealistically small fluctuations in population abundance, and a strong positive correlation between a species' abundance and its age, contrary to empirical evidence. Models allowing for the robust persistence of large communities of interacting competitors are lacking. Here we show that very diverse communities could persist thanks to the stabilizing role of higher-order interactions, in which the presence of a species influences the interaction between other species. Although higher-order interactions have been studied for decades, their role in shaping ecological communities is still unclear. The inclusion of higher-order interactions in competitive network models stabilizes dynamics, making species coexistence robust to the perturbation of both population abundance and parameter values. We show that higher-order interactions have strong effects in models of closed ecological communities, as well as of open communities in which new species are constantly introduced. In our framework, higher-order interactions are completely defined by pairwise interactions, facilitating empirical parameterization and validation of our models.

Situating commercial determinants of health in their historical context: a qualitative study of sugar-sweetened beverages in Jamaica.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of mortality across the Caribbean and similar regions. Structural determinants include a marked increase in the dependency on food imports, and the proliferation of processed foods, including sugar-sweetened beverages (SSBs). We focused on Jamaica as a case study and the health challenge of SSBs, and situated contemporary actions, experiences and policies within their historical context to investigate underlying drivers of commercial determinants of health and attempts to counter them. We asked: how can a historical perspective of the drivers of high level SSB consumption in Jamaica contribute to an enhanced understanding of the context of public health policies aimed at reducing their intake? METHODS: An ethnographic approach with remote data collection included online semi-structured interviews and workshops with 22 local experts and practitioners of health, agriculture and nutrition in Jamaica and attending relevant regional public webinars on SSBs and NCD action in the Caribbean. Our analysis was situated within a review of historical studies of Caribbean food economies with focus on the twentieth century. Jamaican and UK-based researchers collected and ethnographically analysed the data, and discussed findings with the wider transdisciplinary team. RESULTS: We emphasise three key areas in which historical events have shaped contextual factors of SSB consumption. Trade privileged sugar as a cash crop over food production during Jamaica's long colonial history, and trade deregulation since the 1980s through structural adjustment opened markets to transnational companies. These changes increased Jamaican receptiveness to the mass advertisement and marketing of these companies, whilst long-standing power imbalances hampered taxation and regulation in contemporary public health actions. Civil society efforts were important for promoting structural changes to curb overconsumption of SSBs and decentring such entrenched power relations. CONCLUSION: The contemporary challenge of SSBs in Jamaica is a poignant case study of commercial determinants of health and the important context of global market-driven economies and the involvement of private sector interests in public health policies and governance. Historically contextualising these determinants is paramount to making sense of the sugar ecology in Jamaica today and can help elucidate entrenched power dynamics and their key actors.

Functional biomechanical comparison of Latarjet vs. distal tibial osteochondral allograft for anterior glenoid defect reconstruction.

INTRODUCTION: Glenoid reconstruction is indicated for recurrent glenohumeral instability with significant glenoid bone deficiency. Coracoid autograft (Latarjet) and distal tibial osteochondral allograft (DTA) reconstructions have been used to successfully restore glenohumeral stability. Relative advantages and disadvantages associated with each reconstruction technique have been described. However, direct comparisons of functional glenohumeral biomechanics associated with Latarjet vs. DTA reconstruction are lacking. This study was designed to compare these 2 glenoid reconstruction techniques with respect to joint kinematics and cartilage pressure mapping using a robotic testing system. METHODS: In accordance with institutional review board policies, human cadaveric shoulders (n = 8) were cyclically tested in the neutral position and 90° of external rotation with 60° and 90° of abduction under a 45-N joint-compression load to measure clinically relevant translations, loads, and torques. Joint contact pressure maps were obtained under a 120-N joint-compression load using pressure mapping sensors. After confirming that a 25% anterior glenoid defect resulted in glenohumeral dislocation, testing was performed to compare 3 conditions: native intact glenoid, 25% anterior glenoid defect with Latarjet reconstruction, and 25% anterior glenoid defect with DTA reconstruction. Analyses of variance and t tests were used to analyze data with statistical significance set at P < .05. RESULTS: Significant differences in anterior translation, inferior drawer, anterior drawer, compression loads, horizontal abduction, negative elevation (adduction), and external rotation torques during cyclical testing in 90° of external rotation with 60° and/or 90° of abduction were noted when comparing the 2 different glenoid bone reconstruction techniques to native, intact shoulders. The only significant difference between Latarjet and DTA reconstructions for measured translations, loads, and torques was a significantly higher absolute maximum compressive load for Latarjet compared to DTA at 60° of abduction. CONCLUSION: Latarjet coracoid osseous autograft and distal tibial osteochondral allograft reconstructions of large (25%) glenoid bone defects prevent failure (dislocation) and are associated with significant glenohumeral kinematic differences that largely confer less translation, load, and torque on the joint in abduction when compared to the native state. These findings suggest that these 2 surgical techniques exhibit similar glenohumeral kinematics such that each provides adequate functional stability following anterior glenoid bone reconstruction. Joint compression load and articular contact pressure distribution may favor distal tibial osteochondral allograft reconstruction for treatment of large (25%) anterior glenoid bone defects associated with shoulder instability.

Virtual Reality Job Interview Training for Adults Receiving Prison-Based Employment Services: A Randomized Controlled Feasibility and Initial Effectiveness Trial.

Returning citizens struggle to obtain employment after release from prison, and navigating job interviews is a critical barrier they encounter. Implementing evidence-based interview training is a major gap in prison-based vocational services. We conducted a randomized controlled trial (RCT) to evaluate the feasibility and initial effectiveness of Virtual Reality Job Interview Training within two prisons. Forty-four male returning citizens were randomized to receive service-as-usual (SAU) with VR-JIT (SAU+VR-JIT, n = 28) or SAU (n = 16). Participants reported VR-JIT was highly acceptable and usable. SAU+VR-JIT, as compared to SAU, had significant improvements (with large effect sizes) in interview skills, interview training motivation, and interview anxiety (all p < .05; ηp2 > .15), and greater employment by 6-month follow-up (OR = 7.4, p = .045). VR-JIT can potentially help fill a major gap in prison-based services. Future research is needed to validate VR-JIT effectiveness and evaluate VR-JIT implementation strategies within prisons.

Development and Psychometric Properties of Self-Reported Job Interview Skills and Job Interview Anxiety for Autistic Transition-Age Youth.

BACKGROUND: The study of job interview training is an emerging area among transition-age autistic youth who face significant challenges when navigating job interviews. The autism field has limited measures that have undergone rigorous psychometric evaluation. OBJECTIVE: We sought to evaluate the psychometric properties of adapted self-report measures assessing job interview skills and job interview anxiety. METHODS: As part of two parent randomized controlled trials, eighty-five transition-age autistic youth completed measures related to the strength of their job interview skills and their level of job interview anxiety. We conducted classical test theory analyses, exploratory and confirmatory factor analyses, and Rasch model analytic and calibration analyses. Pearson correlations were used to establish concurrent, divergent, and criterion validity by correlating these scales with measures of social differences, depressive symptoms, behaviors, neuropsychological functioning, and work history. RESULTS: Our analyses yielded two brief and reliable scales: Measure of Job Interview Skills (MOJO-iSkills) and Measure of Job Interview Anxiety (MOJO-iAnxiety), which demonstrated initial concurrent, divergent, and criterion validities when correlated with measures of depressive symptoms, social differences, internalizing and externalizing behavior, and work history. CONCLUSIONS: This study presents initial evidence that MOJO-iSkills and MOJO-iAnxiety have acceptable psychometric properties supporting they can be used to reliably and validly assess job interview skills and interview anxiety.

Mixed methods implementation evaluation of virtual interview training for transition-age autistic youth in pre-employment transition services.

BACKGROUND: Autistic transition-age youth are employed at rates far lower than their non-disabled peers as well as youth with other disabilities. Meanwhile, very few studies have evaluated the implementation of job interviewing practices within pre-employment transition services. OBJECTIVE: We conducted an initial implementation evaluation as part of a Type I hybrid randomized controlled effectiveness-implementation trial where we trained teachers to deliver Virtual Interview Training for Transition-Age Youth (VIT-TAY) within five pre-employment transition services programs. METHODS: We used mixed methods to evaluate leader (n=5), teacher (n=15) and autistic transition age youth (n=48) perceptions of VIT-TAY. We used descriptive statistics and thematic network analysis to evaluate survey data. Mixed methods integration was then performed to make comparisons between quantitative and qualitative results. RESULTS: Quantitative survey data revealed that leaders and teachers found VIT-TAY to be highly acceptable and appropriate for pre-employment transition services; findings which were confirmed via thematic network analysis of qualitative interview data. Autistic students reported via quantitative surveys that VIT-TAY was acceptable and usable, which was confirmed via thematic network analysis of open-ended survey data. CONCLUSIONS: This initial implementation evaluation can be used to inform a larger scale implementation evaluation of VIT-TAY in schools.