Clinical Outcomes of Prone Transpsoas Lumbar Interbody Fusion: A 1-Year Follow-Up.

BACKGROUND: Lateral lumbar interbody fusion (LLIF) is commonly used to address various lumbar pathologies. LLIF using the prone transpsoas (PTP) approach has several potential advantages, allowing simultaneous access to the anterior and posterior columns of the spine. The aim of this study was to report the 1-year outcomes of LLIF via PTP. METHODS: This is a retrospective review of 97 consecutive patients who underwent LLIF via PTP. Radiographic parameters, including lumbar-lordosis, segmental-lordosis, anterior disc height, and posterior disc height, were measured on preoperative, initial-postoperative, and 1-year postoperative imaging. Patient-reported outcomes measures, including Oswestry Disability Index, visual analog scale (VAS), pain EQ5D, and postoperative complications, were reviewed. RESULTS: Ninety-seven consecutive patients underwent 161 levels of LLIF. Fifty-seven percent underwent 1-level LLIF, 30% 2-level LLIF, 6% 3-level LLIF, and 7% 4-level LLIF. The most common level was L4 to L5 (35%), followed by L3 to L4 (33%), L2 to L3 (21%), and L1 to L2 (11%). Significant improvements were noted at initial and 1-year postoperative periods in lumbar-lordosis (2° ± 10°, P = 0.049; 3° ± 9°, P = 0.005), segmental-lordosis (6° ± 5°, P < 0.001; 5° ± 5°, P < 0.001), anterior disc height (8 mm ± 4 mm, P < 0.001; 7 mm ± 4 mm, P < 0.001), and posterior disc height (3 mm ± 2 mm, P < 0.001; 3 mm ± 2 mm, P < 0.001). Significant improvements were seen in Oswestry Disability Index at 6 weeks (P = 0.002), 6 months (P < 0.001), and 1 year (P < 0.001) postoperatively; pain EQ5D at 6 weeks (P < 0.001), 6 months (P < 0.001), and 1 year (P < 0.001) postoperatively; and leg and back visual analog scale at 2 weeks (P < 0.001), 6 months (P < 0.001), and 1 year (P < 0.001) postoperatively. The average length of stay was 2.5 days, and the most common complications were ipsilateral hip flexor pain (46%), weakness (59%), and contralateral hip flexor pain (29%). CONCLUSION: PTP is a novel way of performing LLIF. These 1-year data support that PTP is an effective, safe, and viable approach with similar patient-reported outcome measures and complications profiles as LLIF performed in the lateral decubitus position.

eEF1A2 promotes PTEN-GSK3ß-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer.

The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis. Here, we found that eEF1A2 exhibited oncogenic or tumor-suppressor functions depending on its interaction with METTL13 or the phosphatase PTEN, respectively. METTL13 and PTEN competed for interaction with eEF1A2 in the same structural domain. PTEN-bound eEF1A2 promoted the ubiquitination and degradation of the mitosis-promoting Aurora kinase A in the S and G2 phases of the cell cycle. eEF1A2 bridged the interactions between the SKP1-CUL1-FBXW7 (SCF) ubiquitin ligase complex, the kinase GSK3ß, and Aurora-A, thereby facilitating the phosphorylation of Aurora-A in a degron site that was recognized by FBXW7. Genetic ablation of Eef1a2 or Pten in mice resulted in a greater abundance of Aurora-A and increased cell cycling in mammary tumors, which was corroborated in breast cancer tissues from patients. Reactivating this pathway using fimepinostat, which relieves inhibitory signaling directed at PTEN and increases FBXW7 expression, combined with inhibiting Aurora-A with alisertib, suppressed breast cancer cell proliferation in culture and tumor growth in vivo. The findings demonstrate a therapeutically exploitable, tumor-suppressive role for eEF1A2 in breast cancer.

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta.

The initial step in estrogen-regulated transcription is the binding of a ligand to its cognate receptors, named estrogen receptors (ERα and ERß). Phytochemicals present in foods and environment can compete with endogenous hormones to alter physiological responses. We screened 224 flavonoids in our engineered biosensor ERα and ERß PRL-array cell lines to characterize their activity on several steps of the estrogen signaling pathway. We identified 83 and 96 flavonoids that can activate ERα or ERß, respectively. While most act on both receptors, many appear to be subtype-selective, including potent flavonoids that activate ER at sub-micromolar concentrations. We employed an orthogonal assay using a transgenic zebrafish in vivo model that validated the estrogenic potential of these compounds. To our knowledge, this is the largest study thus far on flavonoids and the ER pathway, facilitating the identification of a new set of potential endocrine disruptors acting on both ERα and ERß.

C5 nerve root palsy (without prior cervical decompression) case series: 9 patients with critical delay to presentation.

BACKGROUND: Distinguishing between cervical nerve root and intrinsic shoulder pathology can be a difficult task given the overlapping and often coexisting symptoms. OBJECTIVE: The objective of this study was to highlight the often-complicated presentation of these symptoms and the subsequent potential for delay in care regarding this subset of patients. METHODS: A total of 9 patients, managed by one of two different surgeons, were identified with a history of C5 nerve root palsy. A chart review was conducted, and the following information was recorded: presenting complaint, time from symptom onset to diagnosis, time from symptom onset to presentation to a spine surgeon, first specialist seen for symptoms, non-spinal advanced imaging and treatment conducted before diagnosis, preoperative and postoperative exam, time to recovery, and type of surgery. RESULTS: We observed an average time from onset of symptoms to presentation to a spine surgeon to be 31.6 weeks. These patients' time to full recovery after cervical decompression was 15 weeks. CONCLUSION: : We observed a critical delay to presentation in this series of patients with C5 nerve palsy. C5 nerve palsy should remain an elemental part of the differential diagnosis in the setting of any shoulder or neck pain presenting with weakness.

A novel ERß high throughput microscopy platform for testing endocrine disrupting chemicals.

In this study we present an inducible biosensor model for the Estrogen Receptor Beta (ERß), GFP-ERß:PRL-HeLa, a single-cell-based high throughput (HT) in vitro assay that allows direct visualization and measurement of GFP-tagged ERß binding to ER-specific DNA response elements (EREs), ERß-induced chromatin remodeling, and monitor transcriptional alterations via mRNA fluorescence in situ hybridization for a prolactin (PRL)-dsRED2 reporter gene. The model was used to accurately (Z' = 0.58-0.8) differentiate ERß-selective ligands from ERα ligands when treated with a panel of selective agonists and antagonists. Next, we tested an Environmental Protection Agency (EPA)-provided set of 45 estrogenic reference chemicals with known ERα in vivo activity and identified several that activated ERß as well, with varying sensitivity, including a subset that is completely novel. We then used an orthogonal ERE-containing transgenic zebrafish (ZF) model to cross validate ERß and ERα selective activities at the organism level. Using this environmentally relevant ZF assay, some compounds were confirmed to have ERß activity, validating the GFP-ERß:PRL-HeLa assay as a screening tool for potential ERß active endocrine disruptors (EDCs). These data demonstrate the value of sensitive multiplex mechanistic data gathered by the GFP-ERß:PRL-HeLa assay coupled with an orthogonal zebrafish model to rapidly identify environmentally relevant ERß EDCs and improve upon currently available screening tools for this understudied nuclear receptor.

Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

PURPOSE: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation. METHODS: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation. RESULTS: Part 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1. CONCLUSIONS: While there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.

Gene transcription regulation by ER at the single cell and allele level.

In this short review we discuss the current view of how the estrogen receptor (ER), a pivotal member of the nuclear receptor superfamily of transcription factors, regulates gene transcription at the single cell and allele level, focusing on in vitro cell line models. We discuss central topics and new trends in molecular biology including phenotypic heterogeneity, single cell sequencing, nuclear phase separated condensates, single cell imaging, and image analysis methods, with particular focus on the methodologies and results that have been reported in the last few years using microscopy-based techniques. These observations augment the results from biochemical assays that lead to a much more complex and dynamic view of how ER, and arguably most transcription factors, act to regulate gene transcription.

Analysis and Modeling of Early Estradiol-induced GREB1 Single Allele Gene Transcription at the Population Level.

Single molecule fluorescence in situ hybridization (smFISH) can be used to visualize transcriptional activation at the single allele level. We and others have applied this approach to better understand the mechanisms of activation by steroid nuclear receptors. However, there is limited understanding of the interconnection between the activation of target gene alleles inside the same nucleus and within large cell populations. Using the GREB1 gene as an early estrogen receptor (ER) response target, we applied smFISH to track E2-activated GREB1 allelic transcription over early time points to evaluate potential dependencies between alleles within the same nucleus. We compared two types of experiments where we altered the initial status of GREB1 basal transcription by treating cells with and without the elongation inhibitor flavopiridol (FV). E2 stimulation changed the frequencies of active GREB1 alleles in the cell population independently of FV pre-treatment. In FV treated cells, the response time to hormone was delayed, albeit still reaching at 90 minutes the same levels as in cells not treated by FV. We show that the joint frequencies of GREB1 activated alleles observed at the cell population level imply significant dependency between pairs of alleles within the same nucleus. We identify probabilistic models of joint alleles activations by applying a principle of maximum entropy. For pairs of alleles, we have then quantified statistical dependency by computing their mutual information. We have then introduced a stochastic model compatible with allelic statistical dependencies, and we have fitted this model to our data by intensive simulations. This provided estimates of the average lifetime for degradation of GREB1 introns and of the mean time between two successive transcription rounds. Our approach informs on how to extract information on single allele regulation by ER from within a large population of cells, and should be applicable to many other genes. AUTHOR SUMMARY: After application of a gene transcription stimulus, in this case the hormone 17 ß -estradiol, on large populations of cells over a short time period, we focused on quantifying and modeling the frequencies of GREB1 single allele activations. We have established an experimental and computational pipeline to analyze large numbers of high resolution smFISH images to detect and monitor active GREB1 alleles, that can be translatable to any target gene of interest. A key result is that, at the population level, activation of individual GREB1 alleles within the same nucleus do exhibit statistically significant dependencies which we quantify by the mutual information between activation states of pairs of alleles. After noticing that frequencies of joint alleles activations observed over our large cell populations evolve smoothly in time, we have defined a population level stochastic model which we fit to the observed time course of GREB1 activation frequencies. This provided coherent estimates of the mean time between rounds of GREB1 transcription and the mean lifetime of nascent mRNAs. Our algorithmic approach and experimental methods are applicable to many other genes.

Binary Classification of the Endocrine Disrupting Chemicals by Artificial Neural Networks.

We develop a machine learning framework that integrates high content/high throughput image analysis and artificial neural networks (ANNs) to model the separation between chemical compounds based on their estrogenic receptor activity. Natural and man-made chemicals have the potential to disrupt the endocrine system by interfering with hormone actions in people and wildlife. Although numerous studies have revealed new knowledge on the mechanism through which these compounds interfere with various hormone receptors, it is still a very challenging task to comprehensively evaluate the endocrine disrupting potential of all existing chemicals and their mixtures by pure in vitro or in vivo approaches. Machine learning offers a unique advantage in the rapid evaluation of chemical toxicity through learning the underlying patterns in the experimental biological activity data. Motivated by this, we train and test ANN classifiers for modeling the activity of estrogen receptor-α agonists and antagonists at the single-cell level by using high throughput/high content microscopy descriptors. Our framework preprocesses the experimental data by cleaning, scaling, and feature engineering where only the middle 50% of the values from each sample with detectable receptor-DNA binding is considered in the dataset. Principal component analysis is also used to minimize the effects of experimental noise in modeling where these projected features are used in classification model building. The results show that our ANN-based nonlinear data-driven framework classifies the benchmark agonist and antagonist chemicals with 98.41% accuracy.

Machine Learning Methods for Endocrine Disrupting Potential Identification Based on Single-Cell Data.

Humans are continuously exposed to a variety of toxicants and chemicals which is exacerbated during and after environmental catastrophes such as floods, earthquakes, and hurricanes. The hazardous chemical mixtures generated during these events threaten the health and safety of humans and other living organisms. This necessitates the development of rapid decision-making tools to facilitate mitigating the adverse effects of exposure on the key modulators of the endocrine system, such as the estrogen receptor alpha (ERα), for example. The mechanistic stages of the estrogenic transcriptional activity can be measured with high content/high throughput microscopy-based biosensor assays at the single-cell level, which generates millions of object-based minable data points. By combining computational modeling and experimental analysis, we built a highly accurate data-driven classification framework to assess the endocrine disrupting potential of environmental compounds. The effects of these compounds on the ERα pathway are predicted as being receptor agonists or antagonists using the principal component analysis (PCA) projections of high throughput, high content image analysis descriptors. The framework also combines rigorous preprocessing steps and nonlinear machine learning algorithms, such as the Support Vector Machines and Random Forest classifiers, to develop highly accurate mathematical representations of the separation between ERα agonists and antagonists. The results show that Support Vector Machines classify the unseen chemicals correctly with more than 96% accuracy using the proposed framework, where the preprocessing and the PCA steps play a key role in suppressing experimental noise and unraveling hidden patterns in the dataset.

Helping families heal in substance use treatment: A qualitative study about the role of peer support specialists with client families.

INTRODUCTION: Peer support specialists (PSS) are people with previous psychiatric illness or substance use disorders who use their experience to support those facing similar hardships. PSS offer a range of beneficial outcomes to both the PSS and clients. The most immediate social connections to those seeking treatment are often their families, yet no PSS studies are inclusive of family involvement. Strong theoretical and empirical support exists for family involvement in addiction treatment, but no studies to date on families in substance use treatment include PSS. This study offers a first look at PSS's experiences with client families. We aimed to describe experiences and attitudes of PSS in working with families of those seeking substance use treatment. METHODS: This qualitative study included 25 adult PSS with at least 1 year of work experience in substance use treatment and state credentialing board certification. Participants had one interview either in a focus group format or individually. The recruitment and data collection phase lasted from November 2020 to June 2021. The semi-structured interview protocol included six main questions and interviews lasted 60 to 75 min. Upon completion of each interview, the recordings were transcribed and inductively coded. Thematic analysis of the codes identified overarching themes and their implications were described with associated quotes. RESULTS: Thematic analysis generated three interrelated themes. First, participants described the various ways they often work with the families of their clients, which seemed to be dependent on the age of the client. Second, participants identified the negative aspects of working with families such as family drama, stress, and co-dependency issues. Last, the third theme identified the ways in which PSS assist families in healing from the effects of addiction. The themes identify a complicated and conflicting approach to work with families. Overall, it seemed PSS were operating on their own experiences or suggestions given by supervisors to guide them with no training on how to approach families. CONCLUSIONS: This study highlights a deficit in PSS training on their role with families, family intervention, and the impact of family on substance use treatment for adults and youth. More research needs to establish the PSS role with families and with clients from marginalized backgrounds. Credentialing and national associations that support PSS should develop additional training and education opportunities related to working with families for PSS, supervisors, and organizational leadership who employ PSS for substance use treatment.

Biomechanical evaluation of subscapularis peel repairs augmented with the long head of the biceps tendon for anatomic total shoulder arthroplasty.

BACKGROUND: Subscapularis failure is a troublesome complication following anatomic total shoulder arthroplasty (aTSA). Commonly discarded during aTSA, the long head of the biceps tendon (LHBT) may offer an efficient and cheap autograft for the augmentation of the subscapularis repair during aTSA. The purpose of this study was to biomechanically compare a standard subscapularis peel repair to 2 methods of subscapularis peel repair augmented with LHBT. METHODS: 18 human cadaveric shoulders (61 ± 9 years of age) were used in this study. Shoulders were randomly assigned to biomechanically compare subscapularis peel repair with (1) traditional single-row repair, (2) single row with horizontal LHBT augmentation, or (3) single row with V-shaped LHBT augmentation. Shoulders underwent biomechanical testing on a servohydraulic testing system to compare cyclic displacement, load to failure, and stiffness. RESULTS: There were no significant differences in the cyclic displacement between the 3 techniques in the superior, middle, or inferior portion of the subscapularis repair (P > .05). The horizontal (436.7 ± 113.3 N; P = .011) and V-shape (563.3 ± 101.0 N; P < .001) repair demonstrated significantly greater load to failure compared with traditional repair (344.4 ± 82.4 N). The V-shape repair had significantly greater load to failure compared to the horizontal repair (P < .001). The horizontal (61.6 ± 8.4 N/mm; P < .001) and the V-shape (62.8 ± 6.1; P < .001) repairs demonstrated significantly greater stiffness compared to the traditional repair (47.6 ± 6.2 N). There was no significant difference in the stiffness of the horizontal and V-shape repairs (P = .770). CONCLUSIONS: Subscapularis peel repair augmentation with LHBT autograft following aTSA confers greater time zero load to failure and stiffness when compared to a standard subscapularis peel repair.

Arthroscopic Rotator Cuff Repair: A Review of Surgical Techniques and Outcomes.

Arthroscopic rotator cuff repair (ARCR) has become the gold standard management for rotator cuff repair. Double-row repairs have shown increased biomechanical strength and enhanced anatomic footprint coverage. The advancement of knotless techniques has led to decreased operating room time and reduced overall costs. We prefer a suture-bridging double-row repair for most rotator cuff repairs and incorporate a knotless medial mattress sutures (double-pulley technique) for additional support as needed.

Sensitive image-based chromatin binding assays using inducible ERα to rapidly characterize estrogenic chemicals and mixtures.

The United States Environmental Protection Agency (EPA) has been pursuing new high throughput in vitro assays to characterize endocrine disrupting chemicals (EDCs) that interact with estrogen receptor signaling. We characterize two new PRL-HeLa cell models expressing either inducible C-terminal (iGFP-ER) or N-terminal (iER-GFP) tagged estrogen receptor-α (ERα) that allows direct visualization of chromatin binding. These models are an order of magnitude more sensitive, detecting 87 - 93% of very weak estrogens tested compared to only 27% by a previous PRL-HeLa variant and compares favorably to the 73% detected by an EPA-developed computational model using in vitro data. Importantly, the chromatin binding assays distinguished agonist- and antagonist-like phenotypes without activity specific assays. Finally, analysis of complex environmentally relevant chemical mixtures demonstrated how chromatin binding data can be used in risk assessment models to predict activity. These new assays should be a useful in vitro tool to screen for estrogenic activity.

Quality Control for Single Cell Imaging Analytics Using Endocrine Disruptor-Induced Changes in Estrogen Receptor Expression.

BACKGROUND: Diverse toxicants and mixtures that affect hormone responsive cells [endocrine disrupting chemicals (EDCs)] are highly pervasive in the environment and are directly linked to human disease. They often target the nuclear receptor family of transcription factors modulating their levels and activity. Many high-throughput assays have been developed to query such toxicants; however, single-cell analysis of EDC effects on endogenous receptors has been missing, in part due to the lack of quality control metrics to reproducibly measure cell-to-cell variability in responses. OBJECTIVE: We began by developing single-cell imaging and informatic workflows to query whether the single cell distribution of the estrogen receptor-α (ER), used as a model system, can be used to measure effects of EDCs in a sensitive and reproducible manner. METHODS: We used high-throughput microscopy, coupled with image analytics to measure changes in single cell ER nuclear levels on treatment with ∼100 toxicants, over a large number of biological and technical replicates. RESULTS: We developed a two-tiered quality control pipeline for single cell analysis and tested it against a large set of biological replicates, and toxicants from the EPA and Agency for Toxic Substances and Disease Registry lists. We also identified a subset of potentially novel EDCs that were active only on the endogenous ER level and activity as measured by single molecule RNA fluorescence in situ hybridization (RNA FISH). DISCUSSION: We demonstrated that the distribution of ER levels per cell, and the changes upon chemical challenges were remarkably stable features; and importantly, these features could be used for quality control and identification of endocrine disruptor toxicants with high sensitivity. When coupled with orthogonal assays, ER single cell distribution is a valuable resource for high-throughput screening of environmental toxicants. https://doi.org/10.1289/EHP9297.

Arthroscopic rotator cuff repair with biologically enhanced patch augmentation.

OBJECTIVE: The purpose of this guide is to illustrate an arthroscopic rotator cuff repair (RCR) with two techniques for biologically enhanced patch augmentation. INDICATIONS: Massive rotator cuff tears (> 5 cm) and revision RCR. CONTRAINDICATIONS: Active joint or systemic infection; severe fatty muscle atrophy; severe glenohumeral arthropathy; American Society of Anesthesiologists Physical Status (ASA PS) IV. SURGICAL TECHNIQUE: Dermal allograft patch augmented with concentrated bone marrow aspirate (cBMA), platelet-rich plasma (PRP) and platelet-poor plasma (PPP); or Regeneten patch augmented with bursa, PRP, PPP, and autologous thrombin. POSTOPERATIVE MANAGEMENT: A 30° abduction sling for 6 weeks; unrestricted active-assisted external rotation and forward elevation after 12 weeks; focus on restoration of scapular stability and strength. RESULTS: A total of 22 patients received revision massive RCR using a dermal allograft patch enhanced with cBMA and PRP with a mean follow-up of 2.5 years (1.0-5.8 years). There was a significant improvement in the preoperative Simple Shoulder Test (SST). There was also a trend towards improved pain and American Shoulder and Elbow Surgeons (ASES) Shoulder Score. In this cohort, 45% reached the minimal clinically important difference (MCID), 41% achieved substantial clinical benefit (SCB), and 32% had a patient-acceptable symptomatic state (PASS) for the ASES score. Preliminary data using the Regeneten patch technique with bursa, PRP, PPP, and autologous thrombin was prospectively collected in five patients between 05/2020 and 03/2021 at the author's institution. Mean follow-up was 6.5 ± 1.3 (6-8 months). There was an improvement from preop to postop in pain, ASES, SANE, Constant-Murley (CM) score and active range of motion.

Three-Dimensional Footprint Mapping of the Deltoid and Trapezius: Anatomic Pearls for Acromioclavicular Joint Reconstruction.

PURPOSE: To perform a quantitative anatomic evaluation of the deltoid and trapezius footprints in relation to the lateral clavicle and acromioclavicular (AC) joint capsule to assist in surgical technique of AC joint reconstructions. METHODS: Fourteen fresh-frozen human cadaveric shoulders from 9 donors were analyzed. Meticulous dissection of the deltoid origin and trapezius insertions to the clavicle and AC joint was performed. Footprints were reconstructed using a MicroScribe digitizer. The inferior extension of the deltoid origin beneath the lateral clavicle and the footprints of the deltoid and trapezius onto the acromioclavicular ligamentous complex (ACLC) were quantified. Reproducibility was assessed by redigitizing 5 shoulders in a blinded and random fashion. RESULTS: The anterior deltoid fibers extended on average 4.0 ± 1.6 mm inferiorly with respect to the anteroinferior clavicular ridge and attached to 90.9 ± 7.3% of the anterior ACLC. The trapezius inserted onto the posterior and superior ACLC, covering 15.3 ± 3.4% of the anterior-posterior width of the superior capsule. The deltopectoral interval was 6 cm, or 37% the length of the clavicle from the distal end of the clavicle. CONCLUSIONS: The deltoid has superior, anterior, and not as well described, inferior attachments to the lateral clavicle. Furthermore, the deltoid and trapezius muscles have intimate attachments to the AC joint capsule, particularly the trapezius to the posterior and posterosuperior capsule. Lastly, the deltoid origin attaches to the lateral 6 cm of the clavicle. CLINICAL RELEVANCE: Subperiosteal elevation of the deltoid off the lateral clavicle starting superiorly, anteriorly, and lastly inferiorly will reduce deltoid muscle injury and improve visibility of the coracoid process during reconstruction. Furthermore, knowledge of the attachments of the deltoid and trapezius to the ACLC may help limit iatrogenic injury to these dynamic stabilizers.

Minimum 10-Year Clinical Outcomes After Arthroscopic 270° Labral Repair in Traumatic Shoulder Instability Involving Anterior, Inferior, and Posterior Labral Injury.

BACKGROUND: Current literature reports highly satisfactory short- and midterm clinical outcomes in patients with arthroscopic 270° labral tear repairs. However, data remain limited on long-term clinical outcomes and complication and redislocation rates in patients with traumatic shoulder instability involving anterior, inferior, and posterior labral injury. PURPOSE: To investigate, at a minimum follow-up of 10 years, the clinical outcomes, complications, and recurrent instability in patients with 270° labral tears involving the anterior, inferior, and posterior labrum treated with arthroscopic stabilization using suture anchors. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective outcomes study was completed for all patients with a minimum 10-year follow-up who underwent arthroscopic 270° labral tear repairs with suture anchors by a single surgeon. Outcome measures included pre- and postoperative Rowe score, American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test, visual analog scale for pain, and Single Assessment Numeric Evaluation (SANE). Western Ontario Shoulder Instability Index (WOSI) scores were collected postoperatively. Complication data were collected, including continued instability, subluxation or dislocation events, and revision surgery. Failure was defined as any cause of revision surgery. RESULTS: In total, 21 patients (mean ± SD age, 27.1 ± 9.6 years) with 270° labral repairs were contacted at a minimum 10-year follow-up. All outcome measures showed statistically significant improvements as compared with those preoperatively: Rowe (53.9 ± 11.4 to 88.7 ± 8.9; P = .005), ASES (72.9 ± 18.4 to 91.8 ± 10.8; P = .004), Simple Shoulder Test (8.7 ± 2.4 to 11.2 ± 1.0; P = .013), visual analog scale (2.5 ± 2.6 to 0.5 ± 1.1; P = .037), and SANE (24.0 ± 15.2 to 91.5 ± 8.3; P = .043). The mean postoperative WOSI score at minimum follow-up was 256.3 ± 220.6. Three patients had postoperative complications, including a traumatic subluxation, continued instability, and a traumatic dislocation, 2 of which required revision surgery (14.2% failure rate). CONCLUSION: Arthroscopic repairs of 270° labral tears involving the anterior, inferior, and posterior labrum have highly satisfactory clinical outcomes at 10 years, with complication and redislocation rates similar to those reported at 2 years. This suggests that repairs of extensile labral tears are effective in restoring and maintaining mechanical stability of the glenohumeral joint in the long term.

Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α.

Transcription is a highly regulated sequence of stochastic processes utilizing many regulators, including nuclear receptors (NR) that respond to stimuli. Endocrine disrupting chemicals (EDCs) in the environment can compete with natural ligands for nuclear receptors to alter transcription. As nuclear dynamics can be tightly linked to transcription, it is important to determine how EDCs affect NR mobility. We use an EPA-assembled set of 45 estrogen receptor-α (ERα) ligands and EDCs in our engineered PRL-Array model to characterize their effect upon transcription using fluorescence in situ hybridization and fluorescence recovery after photobleaching (FRAP). We identified 36 compounds that target ERα-GFP to a transcriptionally active, visible locus. Using a novel method for multi-region FRAP analysis we find a strong negative correlation between ERα mobility and inverse agonists. Our findings indicate that ERα mobility is not solely tied to transcription but affected highly by the chemical class binding the receptor.