A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling.

Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing under electrical pacing. The plastic platform enabled on-line noninvasive recording of passive tension, active force, contractile dynamics, and Ca2+ transients, as well as endpoint assessments of action potentials and conduction velocity. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and we demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells.

Population Diversity at the Single-Cell Level.

Population-scale single-cell genomics is a transformative approach for unraveling the intricate links between genetic and cellular variation. This approach is facilitated by cutting-edge experimental methodologies, including the development of high-throughput single-cell multiomics and advances in multiplexed environmental and genetic perturbations. Examining the effects of natural or synthetic genetic variants across cellular contexts provides insights into the mutual influence of genetics and the environment in shaping cellular heterogeneity. The development of computational methodologies further enables detailed quantitative analysis of molecular variation, offering an opportunity to examine the respective roles of stochastic, intercellular, and interindividual variation. Future opportunities lie in leveraging long-read sequencing, refining disease-relevant cellular models, and embracing predictive and generative machine learning models. These advancements hold the potential for a deeper understanding of the genetic architecture of human molecular traits, which in turn has important implications for understanding the genetic causes of human disease. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 25 is August 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage.

Heart development is exquisitely sensitive to the precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. However, we currently lack a detailed understanding of how chromatin and gene expression patterns are coordinated during developmental transitions in the cardiac lineage. Here, we interrogated the transcriptome and several histone modifications across the genome during defined stages of cardiac differentiation. We find distinct chromatin patterns that are coordinated with stage-specific expression of functionally related genes, including many human disease-associated genes. Moreover, we discover a novel preactivation chromatin pattern at the promoters of genes associated with heart development and cardiac function. We further identify stage-specific distal enhancer elements and find enriched DNA binding motifs within these regions that predict sets of transcription factors that orchestrate cardiac differentiation. Together, these findings form a basis for understanding developmentally regulated chromatin transitions during lineage commitment and the molecular etiology of congenital heart disease.

Untangling the cortico-thalamo-cortical loop: cellular pieces of a knotty circuit puzzle.

Functions of the neocortex depend on its bidirectional communication with the thalamus, via cortico-thalamo-cortical (CTC) loops. Recent work dissecting the synaptic connectivity in these loops is generating a clearer picture of their cellular organization. Here, we review findings across sensory, motor and cognitive areas, focusing on patterns of cell type-specific synaptic connections between the major types of cortical and thalamic neurons. We outline simple and complex CTC loops, and note features of these loops that appear to be general versus specialized. CTC loops are tightly interlinked with local cortical and corticocortical (CC) circuits, forming extended chains of loops that are probably critical for communication across hierarchically organized cerebral networks. Such CTC-CC loop chains appear to constitute a modular unit of organization, serving as scaffolding for area-specific structural and functional modifications. Inhibitory neurons and circuits are embedded throughout CTC loops, shaping the flow of excitation. We consider recent findings in the context of established CTC and CC circuit models, and highlight current efforts to pinpoint cell type-specific mechanisms in CTC loops involved in consciousness and perception. As pieces of the connectivity puzzle fall increasingly into place, this knowledge can guide further efforts to understand structure-function relationships in CTC loops.

Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models.

WD repeat domain 5 (WDR5) is a core scaffolding component of many multiprotein complexes that perform a variety of critical chromatin-centric processes in the nucleus. WDR5 is a component of the mixed lineage leukemia MLL/SET complex and localizes MYC to chromatin at tumor-critical target genes. As a part of these complexes, WDR5 plays a role in sustaining oncogenesis in a variety of human cancers that are often associated with poor prognoses. Thus, WDR5 has been recognized as an attractive therapeutic target for treating both solid and hematological tumors. Previously, small-molecule inhibitors of the WDR5-interaction (WIN) site and WDR5 degraders have demonstrated robust in vitro cellular efficacy in cancer cell lines and established the therapeutic potential of WDR5. However, these agents have not demonstrated significant in vivo efficacy at pharmacologically relevant doses by oral administration in animal disease models. We have discovered WDR5 WIN-site inhibitors that feature bicyclic heteroaryl P7 units through structure-based design and address the limitations of our previous series of small-molecule inhibitors. Importantly, our lead compounds exhibit enhanced on-target potency, excellent oral pharmacokinetic (PK) profiles, and potent dose-dependent in vivo efficacy in a mouse MV4:11 subcutaneous xenograft model by oral dosing. Furthermore, these in vivo probes show excellent tolerability under a repeated high-dose regimen in rodents to demonstrate the safety of the WDR5 WIN-site inhibition mechanism. Collectively, our results provide strong support for WDR5 WIN-site inhibitors to be utilized as potential anticancer therapeutics.

Editorial Commentary: Anterior Cruciate Ligament Repair or Reconstruction With Internal Bracing, for Properly Indicated Patients, Is Safe, Biocompatible, and Biomimetic.

Anterior cruciate ligament (ACL) reconstruction with internal bracing (IB)-and ACL repair with IB when indicated-reduces graft or repair failure. IB is safe and protects ligament reconstructions and repairs. The IB construct should not be misunderstood as a synthetic ligament. To be effective, suture tape must be independently secured with the knee in full extension, reflecting the terminal length of the ACL. Regardless of graft type, the graft must be cyclically tensioned independent of the IB to allow for creep, and when properly performed, this significantly increases the ultimate tensile strength of the construct and reduces graft elongation, without stress shielding. Thus, the generic term "suture augmentation" may be misleading because the successful results reported apply to the IB technique. In our experience, the failure rate after ACL reconstruction with IB is 1% at the 5-year follow-up period. Notably, these results were achieved without an additional lateral extra-articular procedure.

Elephants in the Room - Analyzing Local Discourses for Sustainable Management of Bannerghatta National Park, South India.

Landscape governance challenges, particularly in peri-urban contexts like the Bannerghatta National Park (BNP) region in South India, exemplify 'wicked' problems due to their inherent complexities. These challenges arise from a mix of conflicting interests, policy ambiguities, and sociocultural dynamics, which often blur the definition of problems and hinder effective solutions. Despite apparent options for resolution, stakeholder disagreements and deep uncertainties about implementation strategies complicate governance. This study, therefore, has two broad objectives. The first objective is to analyze the local discourses surrounding planned policy interventions around the BNP region in South India. Based on the findings, the second objective is to draw insights for sustainable natural resource governance research and practice. We applied Q-methodology to understand the discourses that underpin various conflicts in the rapidly urbanizing elephant corridor at BNP. We elicited information on how various local actors frame solutions to current collective action challenges in the BNP landscape and their perspectives on the proposed eco-sensitive zone notification, as well as the functioning of current policy interventions concerning conservation and development. The study uncovers the micropolitics and power regimes underpinning various natural resource governance challenges and demonstrates the utility of the Q-methodology in bringing diverse perspectives together in response to 'wicked' governance challenges.

Boundary Spanning Methodological Approaches for Collaborative Moose Governance in Eeyou Istchee.

Natural resource governance challenges are often highly complex, particularly in Indigenous contexts. These challenges involve numerous landscape-level interactions, spanning jurisdictional, disciplinary, social, and ecological boundaries. In Eeyou Istchee, the James Bay Cree Territory of northern Quebec, Canada, traditional livelihoods depend on wild food species like moose. However, these species are increasingly being impacted by forestry and other resource development projects. The complex relationships between moose, resource development, and Cree livelihoods can limit shared understandings and the ability of diverse actors to respond to these pressures. Contributing to this complexity are the different knowledge systems held by governance actors who, while not always aligned, have broadly shared species conservation and sustainable development goals. This paper presents fuzzy cognitive mapping (FCM) as a methodological approach used to help elicit and interpret the knowledge of land-users concerning the impacts of forest management on moose habitat in Eeyou Istchee. We explore the difficulties of weaving this knowledge together with the results of moose GPS collar analysis and the knowledges of scientists and government agencies. The ways in which participatory, relational mapping approaches can be applied in practice, and what they offer to pluralistic natural resource governance research more widely, are then addressed.

Axonal Barcode Analysis of Pyramidal Tract Projections from Mouse Forelimb M1 and M2.

Forelimb-related areas of the motor cortex communicate directly to downstream areas in the brainstem and spinal cord via axons that project to and through the pyramidal tract (PT). To better understand the diversity of the brainstem branching patterns of these pyramidal tract projections, we used MAPseq, a molecular barcode technique for population-scale sampling with single-axon resolution. In experiments using mice of both sexes, we first confirmed prior results demonstrating the basic efficacy of axonal barcode identification of primary motor cortex (M1) PT-type axons, including corticobulbar (CBULB) and corticospinal (CSPI) subclasses. We then used multiplexed MAPseq to analyze projections from M1 and M2 (caudal and rostral forelimb areas). The four basic axon subclasses comprising these projections (M1-CSPI, M1-CBULB, M2-CSPI, M2-CBULB) showed a complex mix of differences and similarities in their brainstem projection profiles. This included relatively abundant branching by all classes in the dorsal midbrain, by M2 subclasses in the pons, and by CSPI subclasses in the dorsal medulla. Cluster analysis showed graded distributions of the basic subclasses within the PT class. Clusters were of diversely mixed subclass composition and showed distinct rostrocaudal and/or dorsomedial projection biases. Exemplifying these patterns was a subcluster likely enriched in corticocuneate branches. Overall, the results indicate high yet systematic PT axon diversity at the level of brainstem branching patterns; projections of M1 and M2 appear qualitatively similar, yet with quantitative differences in subclasses and clusters.SIGNIFICANCE STATEMENT Axons of the PT class of cortical projection neurons, which includes corticospinal and corticobulbar neurons, anatomically link motor cortex to brainstem and spinal cord circuits. Both of these subclasses can form branches to brainstem destinations along the way, but the extent and diversity of these branching patterns is incompletely understood. Here, we used MAPseq to tag PT axons with individual molecular barcodes for high-throughput quantification of branching patterns across the brainstem. The results reveal diverse, complex, yet systematic branching patterns of corticospinal and corticobulbar neurons arising from two motor cortex areas, M1 and M2.

Anterior Cruciate Ligament Reconstruction and Accelerated Rehabilitation with InternalBrace™ Augmentation in a Professional Footballer.

INTRODUCTION: Interest in anterior cruciate ligament (ACL) repair has been increasing as an alternative to traditional reconstructive techniques and encouraging results have been demonstrated using internal bracing with suture tape augmentation (FiberTape®, Arthrex, Naples, Florida). ACL repair is challenging if the rupture is mid-substance or distal. We describe the case of a hybrid ACL reconstruction with internal brace augmentation. MATERIALS AND METHODS: This retrospective case report documents the rehabilitation process of a 31-year-old professional footballer who had an isolated ACL rupture. The patient underwent a hybrid ACL reconstruction with bone-patellar tendon-bone autograft and suture tape augmentation 10 days after his injury. A task-based rehabilitation programme defined by six progressive phases relevant to performance-based outcome measures was undertaken. Each phase had clear, functional, progressive goals incorporating exercises to improve mobility, neuromuscular control, strength, and a progressive return to running and sport-specific movements. RESULTS: Using the rehabilitation framework outlined, this player produced excellent results in all objective criteria postoperatively and was able to return to unrestricted full team training in under five months (146 days) following surgery. CONCLUSIONS: This case presentation demonstrates the safe and accelerated return to professional football following ACL reconstruction augmented with internal bracing. The player was able to meet all criteria-based aspects of return to play.

On the architecture of collaboration in inter-organizational natural resource management networks.

This paper reviews the architecture of collaboration that exists within inter-organizational natural resource management (NRM) networks. It presents an integrative conceptual framework designed to help operationalize the multi-level interactions that occur between different dimensions of trust, risk perception, and control as key concepts in inter-organizational collaboration. The objective is to identify and justify a series of propositions considered suitable for assessing inter-organizational NRM network collaboration through empirical work. Such an integrative conceptualization goes beyond the existing trust scholarship related to collaborative NRM, and, we argue, offers a useful starting point for further exploring some of the 'inner' social dynamics affecting collaborative performance using complex systems thinking. To help establish the relevance of the conceptual framework to transboundary resource governance, a survey operationalizing different dimensions of trust, perceived risk, and control is piloted in the Salish Sea, an ecosystem that spans the Canada-US border between British Columbia and Washington State. Key challenges associated with operationalizing the framework and future research needs are identified.

Prevalence of psychiatric disorders among sentenced prisoners in a medium security prison in Ghana: Implications for mental health assessment and service.

BACKGROUND: Extant literature has shown that there is a higher prevalence of mental disorders among prisoners compared to the general population. These findings have, however, mostly been from high-income and westernised cultures. In Ghana, little is known about the extent of psychiatric disorders among prisoners, as is consistent with the dearth of scholarly work in low and middle-income countries. AIMS: Our aim was to determine the prevalence of common mental disorders among sentenced prisoners in the second largest prison in Ghana. METHODS: A cross-sectional survey research design was used in one prison. The Mini International Neuro-Psychiatric Interview questionnaire was used to collect data from men and women serving prison sentences who volunteered for the study. Socio-demographic characteristics and criminal history data were collected using a questionnaire designed by the researchers. RESULTS: Five hundred prisoners participated. Nearly half (246, 49.8%) had at least one psychiatric disorder. The most prevalent disorders were major depression and a range of anxiety disorders (145, 29%, 132, 26% respectively). A smaller proportion recorded high scores on the antisocial personality disorder scale (13%); just 50 (10%) reported using substances in the 12 months before interview, but this is a minimum estimate of such problems as many were already in prison during that time. None of these prisoners, regardless of disorder, had been screened, diagnosed, or treated in prison. CONCLUSIONS: This study contributes to the gap in scholarly literature in low- and middle-income countries on psychiatric disorders in the prison population. It will be important to explore further the extent to which the internationally recognised screening tools used led to under-estimation of psychiatric disorders. The findings are of immediate practical importance nationally as they highlight the need to implement reforms anticipated by the new mental health legislation of 2012 and strategies for interagency working to improve health services and their uptake in the criminal justice system.

Substance use disorders among adults during imprisonment in a medium security prison: Prevalence and risk indicators.

BACKGROUND: Research shows that the prevalence of substance use disorders among the prison population is high globally. Although prisons are highly controlled environments, access to drugs and other substances in prison remains a major problem. Yet, previous research is focussed mainly on the Western context, with the studies generally reporting on lifetime prevalence without reference to whether the disorders are manifest even within the controlled environment. AIMS: To estimate the prevalence of substance use disorders evident while in prison in Ghana and associated risk indicators. For these purposes, substance use disorder was defined by any indication of dependency, or escalating use or socially problematic use during the 12 months of imprisonment prior to the interview. METHODS: The study involved 500 adults (443 men and 57 women) in a medium-security prison in Ghana who had served at least 1 year of a prison sentence. Participants' alcohol use disorder was assessed separately from other substance use disorders which included cannabis, cocaine and other stimulants using the Mini International Neuropsychiatric Interview (MINI); it is a structured interview and diagnostic tool for major psychiatric and substance use disorders in DSM-5 and ICD-10. RESULTS: Two percent of the 500 participants had used alcohol to the level of alcohol use disorder, and 6% had other substance use disorders in 12 months prior to interview and while in prison. Cannabis (4%) and stimulants (3%) were the most frequently reported substance use disorders. Logistic regression model estimates indicate that younger age, prior offending and alcohol use dependence were significantly associated with such disorders in prison. CONCLUSION: In spite of efforts to prevent substance use in prison, nearly one in 10 of these prisoners were using alcohol or illicit drugs to a level indicative of substance use disorders. Our findings suggest that prioritising brief assessment may help identify those in most need of clinical help to limit their alcohol and illicit substance use problems.

Student Veterinarian Perceptions of Community-Based Primary Care Veterinary Clinics in Indigenous Communities in Southern Ontario, Canada.

Community-based primary care veterinary clinics represent an opportunity to benefit multiple populations. Student veterinarians are afforded the opportunity to build technical and non-technical professional skills, while underserved communities are provided with access to companion animal care. The Ontario Veterinary College (OVC), as with many other veterinary colleges across Canada and the United States, has hosted community-based primary care veterinary clinics, including in local Indigenous communities. As these clinics continue and grow, it is critical to evaluate their operation to ensure that they align with community goals and values, adequately support student learning, and do not perpetuate racism and implicit bias. The objective of this study was to explore the perceptions of student veterinarians who had volunteered at community-based primary care veterinary clinics in First Nations communities in southern Ontario, Canada. We used an online survey that consisted of multiple choice and short answer questions focused on motivating factors for involvement, supports available before and during the clinics, exposure to Indigenous cultures, and the challenges and rewards associated with volunteering. Forty-one student veterinarians from OVC completed the survey in January 2020. Most students were motivated to volunteer to make a positive difference in the lives of people and animals and improve their clinical skills. In general, respondents felt adequately prepared for and supported during their experiences but did recommend additional pre-departure instructions on roles and responsibilities. Participants were ambivalent as to whether they had learned about Indigenous culture, with several strongly recommending more cultural sensitivity training. Most students found their experiences rewarding because of the gratitude expressed by clients and the feeling that they had made a difference. We reflect on the potential benefits and challenges of community-based primary care veterinary clinics in light of student responses.

Identification and fine mapping of a major QTL (qRtsc8-1) conferring resistance to maize tar spot complex and validation of production markers in breeding lines.

KEY MESSAGE: A major QTL of qRtsc8-1 conferring TSC resistance was identified and fine mapped to a 721 kb region on chromosome 8 at 81 Mb, and production markers were validated in breeding lines. Tar spot complex (TSC) is a major foliar disease of maize in many Central and Latin American countries and leads to severe yield loss. To dissect the genetic architecture of TSC resistance, a genome-wide association study (GWAS) panel and a bi-parental doubled haploid population were used for GWAS and selective genotyping analysis, respectively. A total of 115 SNPs in bin 8.03 were detected by GWAS and three QTL in bins 6.05, 6.07, and 8.03 were detected by selective genotyping. The major QTL qRtsc8-1 located in bin 8.03 was detected by both analyses, and it explained 14.97% of the phenotypic variance. To fine map qRtsc8-1, the recombinant-derived progeny test was implemented. Recombinations in each generation were backcrossed, and the backcross progenies were genotyped with Kompetitive Allele Specific PCR (KASP) markers and phenotyped for TSC resistance individually. The significant tests for comparing the TSC resistance between the two classes of progenies with and without resistant alleles were used for fine mapping. In BC5 generation, qRtsc8-1 was fine mapped in an interval of ~ 721 kb flanked by markers of KASP81160138 and KASP81881276. In this interval, the candidate genes GRMZM2G063511 and GRMZM2G073884 were identified, which encode an integral membrane protein-like and a leucine-rich repeat receptor-like protein kinase, respectively. Both genes are involved in maize disease resistance responses. Two production markers KASP81160138 and KASP81160155 were verified in 471 breeding lines. This study provides valuable information for cloning the resistance gene, and it will also facilitate the routine implementation of marker-assisted selection in the breeding pipeline for improving TSC resistance.

Evidence and Mass Quantification of Atmospheric Microplastics in a Coastal New Zealand City.

This study investigated the atmospheric deposition of microplastics (MPs) in Auckland, New Zealand, from two sampling sites over a 9-week period. The sizes, morphologies, number counts, and mass concentrations of specific polymers were determined for airborne MPs using a combination of a Nile Red-assisted automated fluorescence microscopy technique in series with pyrolysis-gas chromatography-mass spectrometry (Pyr-GC/MS). This enabled a larger number of MPs to be analyzed from each sample compared to traditional spectroscopic techniques. Microplastic number concentrations increased exponentially with decreasing size. The results show the importance of using consistent methodologies and size cutoffs when comparing microplastic data between studies. Eight polymers were quantified in the atmospheric deposition samples, with polyethylene (PE), polycarbonate (PC), and poly(ethylene terephthalate) (PET) being the most commonly observed. The largest MP deposition rates at an urban rooftop correlated with winds originating from the marine environment with speeds between 15 and 20 m s-1, indicating that airborne MPs in coastal regions may originate from wave-breaking mechanisms. This study represents the first report of using Pyr-GC/MS to determine the chemical compositions and mass concentrations of atmospheric microplastics, along with corresponding data on their sizes, morphologies, and number counts.

The effect of potent CYP2D6 inhibition on the pharmacokinetics and safety of deutetrabenazine in healthy volunteers.

PURPOSE: Deutetrabenazine is a deuterated form of tetrabenazine with a confirmed lower rate of CYP2D6 metabolism of the active metabolites, α- and ß-HTBZ. In this study, we assessed the effect of paroxetine, a potent CYP2D6 inhibitor, on the pharmacokinetics and safety of deutetrabenazine and its metabolites. METHODS: In this open-label sequential drug-drug-interaction study, 24 healthy adults who were CYP2D6 extensive or intermediate metabolizers received a single deutetrabenazine 22.5-mg oral dose on days 1 and 11 and a single paroxetine 20-mg oral daily dose on days 4-12. Pharmacokinetics of deutetrabenazine and its metabolites were assessed on days 1-4 and 11-14. Paroxetine trough concentrations were obtained pre-dose on days 9-13. Safety examinations occurred throughout the study. RESULTS: Paroxetine administered under steady-state conditions, increased exposure of the deuterated active metabolites, α-HTBZ (1.2-fold Cmax and 1.8-fold AUC0-∞) and ß-HTBZ (2.1-fold Cmax and 5.6-fold AUC0-∞), and correspondingly, 1.6-fold Cmax and threefold AUC0-∞ for total (α + ß)-HTBZ. Sixteen subjects reported 45 adverse events and most were mild. Headache was the most common AE reported 8 times by 7 subjects (5 following paroxetine alone; 2 following deutetrabenazine + paroxetine). CONCLUSIONS: Paroxetine-induced increases in exposure to the active deutetrabenazine metabolites were less than those previously reported for tetrabenazine, a finding expected to reduce the burden of drug interaction. In addition, single doses of 22.5 mg deutetrabenazine, when given alone or in the presence of steady-state paroxetine (20 mg daily), were safe.

Satisfactory patient-reported outcomes at 5 years following primary repair with suture tape augmentation for proximal anterior cruciate ligament tears.

PURPOSE: An enhanced understanding of anterior cruciate ligament (ACL) healing and advancements in arthroscopic instrumentation has resulted in a renewed interest in ACL repair. Augmentation of a ligament repair with suture tape reinforces the ligament and acts as a secondary stabilizer. This study assesses the 5-year patient-reported outcomes of primary repair with suture tape augmentation for proximal ACL tears. METHODS: Thirty-seven consecutive patients undergoing ACL repair with suture tape augmentation for an acute proximal rupture were prospectively followed up for a minimum of 5 years. Patients with midsubstance and distal ruptures, poor ACL tissue quality, retracted ACL remnants and multiligament injuries were excluded. Patient-reported outcome measures were collated using the Knee Injury and Osteoarthritis Outcomes Score (KOOS), Visual Analogue Pain Scale (VAS-pain), Veterans RAND 12-Item Health Survey (VR-12) and the Marx Activity Scale. Patients with a re-rupture were identified. RESULTS: Three patients were lost to follow-up leaving 34 patients in the final analysis (91.9%). The mean KOOS at 5 years was 88.5 (SD 13.8) which improved significantly from 48.7 (SD 18.3) preoperatively (p < 0.01). The VAS score improved from 2.3 (SD 1.7) to 1.0 (SD 1.5) and the VR-12 score improved from 35.9 (SD 10.3) to 52.4 (SD 5.9) at 5 years (p < 0.01). However, the Marx activity scale decreased from 12.4 (SD 3.4) pre-injury to 7.3 (SD 5.2) at 5 years (p = 0.02). Six patients had a re-rupture (17.6%) and have since undergone a conventional ACL reconstruction for their revision surgery with no issues since then. These patients were found to be younger and have higher initial Marx activity scores than the rest of the cohort (p < 0.05). CONCLUSION: Primary repair with suture tape augmentation for proximal ACL tears demonstrates satisfactory outcomes in 28 patients (82.4%) at 5-year follow-up. Six patients sustained a re-rupture and have no ongoing problems following treatment with a conventional ACL reconstruction. These patients were significantly younger and had higher initial Marx activity scores. LEVEL OF EVIDENCE: Level IV.

The Intercalated Segment: Does the Triquetrum Move in Synchrony With the Lunate?

PURPOSE: To quantify the relative motion between the lunate and triquetrum during functional wrist movements and to examine the impact of wrist laxity on triquetral motion. METHODS: A digital database of wrist bone anatomy and carpal kinematics for 10 healthy volunteers in 10 different positions was used to study triquetral kinematics. The orientation of radiotriquetral (RT) and radiolunate rotation axes was compared during a variety of functional wrist movements, including radioulnar deviation (RUD) and flexion-extension (FE), and during a hammering task. The motion of the triquetrum relative to the radius during wrist RUD was compared with passive FE range of motion measurements (used as a surrogate measure for wrist laxity). RESULTS: The difference in the orientation of the radiolunate and RT rotation axes was less than 20° during most of the motions studied, except for radial deviation and for the first stage of the hammering task. During wrist RUD, the orientation of the RT rotation axis varied as a function of passive FE wrist range of motion. CONCLUSIONS: The suggestion that the lunate and triquetrum move together as an intercalated segment may be an oversimplification. We observed synchronous movement during some motions, but as the wrist entered RUD, the lunate and triquetrum no longer moved synchronously. These findings challenge the assumptions behind models describing the mechanical function of the carpals. CLINICAL RELEVANCE: Individual-specific differences in the amount of relative motion between the triquetrum and lunate may contribute to the variability in outcomes following lunotriquetral arthrodesis. Variation in triquetral motion patterns may also have an impact on the ability of the triquetrum to extend the lunate, affecting the development of carpal instability.

Medial Patellofemoral Ligament Repair with Suture Tape Augmentation: A Case Series With Five-Year Follow Up.

INTRODUCTION: The medial patellofemoral ligament (MPFL) is the main restraining force against lateral patellar displacement in the first 20 degrees of knee flexion and is often disrupted following patellar subluxation or dislocation. MPFL reconstruction is commonly performed to restore patellar stability but requires autograft harvest with associated donor site morbidity. The aim of this study was to assess the five-year outcomes of MPFL repair performed with suture tape augmentation. MATERIALS AND METHODS: All patients who underwent isolated MPFL repair for recurrent patellar instability between 2011 and 2017 were included. Patients requiring any additional surgery, such as osteotomy, were excluded. Patient-reported outcomes were measured at two-year follow up using the Knee Injury and Osteoarthritis Outcome (KOOS) Score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Pain Scale (VAS-pain), Veterans RAND 12-Item Health Survey (VR-12), Marx Activity Scale, and an overall satisfaction questionnaire. At the end of the study period, any complications or secondary surgeries were determined. RESULTS: Eighteen patients underwent MPFL repair with one lost to follow up. There was a significant improvement in all subscales of the KOOS scoring systems, the WOMAC functional score, and the VR-12 physical score. A significant decrease was seen in the VAS-pain score. A non-significant decrease was seen in the Marx activity scale from pre-injury. The majority of patients reported satisfaction with reduction in pain and return to sporting activities. There were no complications with no further instability episodes. CONCLUSION: This is the first study that describes the five-year follow-up results of patients treated with MPFL repair and suture tape augmentation. Our results show that this technique is an alternative treatment to traditional MPFL reconstruction with comparable outcomes and avoidance of autograft harvest.