Bacterial metallothionein, PmtA, a novel stress protein found on the bacterial surface of Pseudomonas aeruginosa and involved in management of oxidative stress and phagocytosis.

Metallothioneins (MTs) are small cysteine-rich proteins that play important roles in homeostasis and protection against heavy metal toxicity and oxidative stress. The opportunistic pathogen, Pseudomonas aeruginosa, expresses a bacterial MT known as PmtA. Utilizing genetically modified P. aeruginosa PAO1 strains (a human clinical wound isolate), we show that inducing pmtA increases levels of pyocyanin and biofilm compared to other PAO1 isogenic strains, supporting previous results that pmtA is important for pyocyanin and biofilm production. We also show that overexpression of pmtA in vitro provides protection for cells exposed to oxidants, which is a characteristic of inflammation, indicating a role for PmtA as an antioxidant in inflammation. We found that a pmtA clean deletion mutant is phagocytized faster than other PAO1 isogenic strains in THP-1 human macrophage cells, indicating that PmtA provides protection from the phagocytic attack. Interestingly, we observed that monoclonal anti-PmtA antibody binds to PmtA, which is accessible on the surface of PAO1 strains using both flow cytometry and enzyme-linked immunosorbent assay techniques. Finally, we investigated intracellular persistence of these PAO1 strains within THP-1 macrophages cells and found that the phagocytic endurance of PAO1 strains is affected by pmtA expression. These data show for the first time that a bacterial MT (pmtA) can play a role in the phagocytic process and can be found on the outer surface of PAO1. Our results suggest that PmtA plays a role both in protection from oxidative stress and in the resistance to the host's innate immune response, identifying PmtA as a potential therapeutic target in P. aeruginosa infection. IMPORTANCE: The pathogen Pseudomonas aeruginosa is a highly problematic multidrug-resistant (MDR) pathogen with complex virulence networks. MDR P. aeruginosa infections have been associated with increased clinical visits, very poor healthcare outcomes, and these infections are ranked as critical on priority lists of both the Centers for Disease Control and Prevention and the World Health Organization. Known P. aeruginosa virulence factors have been extensively studied and are implicated in counteracting host defenses, causing direct damage to the host tissues, and increased microbial competitiveness. Targeting virulence factors has emerged as a new line of defense in the battle against MDR P. aeruginosa strains. Bacterial metallothionein is a newly recognized virulence factor that enables evasion of the host immune response. The studies described here identify mechanisms in which bacterial metallothionein (PmtA) plays a part in P. aeruginosa pathogenicity and identifies PmtA as a potential therapeutic target.

The Influence of Obesity on Outcomes Following Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-Analysis of 118,331 Patients Internationally.

Background: Given the rising prevalence of obesity, the number of patients with obesity undergoing arthroscopic rotator cuff repair (RCR) will likely increase; however, there have been mixed results in the existing literature with regard to the effect of elevated body mass index (BMI) on functional outcomes and complications. Methods: The patient-reported outcome measures included the visual analog scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, range of motion, and adverse events. Results: Fourteen studies (118,331 patients) were included. There were significant decreases in VAS pain scores for both patients with obesity (mean difference, -3.8 [95% confidence interval (CI), -3.9 to -3.7]; p < 0.001) and patients without obesity (mean difference, -3.2 [95% CI, -3.3 to -3.1]; p < 0.001). There were also significant increases in ASES scores for both patients with obesity (mean difference, 24.3 [95% CI, 22.5 to 26.1]; p < 0.001) and patients without obesity (mean difference, 24.3 [95% CI, 21.4 to 26.0]; p < 0.001). There were also significant increases in ASES scores for both patients with obesity (mean difference, 24.3 [95% CI, 22.5 to 26.1]; p < 0.001) and patients without obesity (mean difference, 24.3 [95% CI, 21.4 to 26.0]; p < 0.001). However, there were no significant differences in final VAS pain scores, ASES scores, or range of motion between the groups. The mean rates of complications were higher among patients with obesity (1.2% ± 1.7%) than among patients without obesity (0.59% ± 0.11%) (p < 0.0001), and the mean rates of postoperative admissions were also higher among patients with obesity (5.9%) than patients without obesity (3.7%) (p < 0.0001). Although the mean rates of reoperation were similar between groups (5.2% ± 2.8% compared with 5.2% ± 4.2%), the meta-analysis revealed lower odds of reoperation in patients without obesity (odds ratio [OR], 0.76 [95% CI, 0.71 to 0.82]). Conclusions: No significant or clinically important differences in postoperative pain, ASES scores, or range of motion were found between patients with and without obesity following arthroscopic RCR. However, populations with obesity had higher rates of complications, postoperative admissions, and reoperation following arthroscopic RCR. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Porcine computational modeling to investigate developmental dysplasia of the hip.

While it is well-established that early detection and initiation of treatment of developmental dysplasia of the hip (DDH) is crucial to successful clinical outcomes, research on the mechanics of the hip joint during healthy and pathological hip development in infants is limited. Quantification of mechanical behavior in both the healthy and dysplastic developing joints may provide insight into the causes of DDH and facilitate innovation in treatment options. In this study, subject-specific three-dimensional finite element models of two pigs were developed: one healthy pig and one pig with induced dysplasia in the right hindlimb. The objectives of this study were: (1) to characterize mechanical behavior in the acetabular articular cartilage during a normal walking cycle by analyzing six metrics: contact pressure, contact area, strain energy density, von Mises stress, principal stress, and principal strain; and (2) to quantify the effect on joint mechanics of three anatomic abnormalities previously identified as related to DDH: variation in acetabular coverage, morphological changes in the femoral head, and changes in the articular cartilage. All metrics, except the contact area, were elevated in the dysplastic joint. Morphological changes in the femoral head were determined to be the most significant factors in elevating contact pressure in the articular cartilage, while the effects of acetabular coverage and changes in the articular cartilage were less significant. The quantification of the pathomechanics of DDH in this study can help identify key mechanical factors that restore normal hip development and can lead to mechanics-driven treatment options.

The Perfect Circle Technique Shows Poor Inter-rater Reliability in Measuring Anterior Glenoid Bone Loss on Magnetic Resonance Imaging.

Purpose: To evaluate the reliability of the perfect circle methodology for measurement of glenoid bone loss in patients with anterior glenohumeral instability. Methods: We performed a chart review of retrospectively collected patients who underwent isolated arthroscopic anterior labral repair between January 1 and June 30, 2021, using our institution's electronic medical records. The inclusion criteria included isolated anterior shoulder instability with anterior labral repair and corroborated tears on magnetic resonance imaging. A total of 9 raters, either sports or shoulder and elbow fellowship-trained orthopaedic surgeons, each evaluated the affected shoulder magnetic resonance imaging scans twice, with a minimum of 2 weeks between measurements. Measurements followed the "perfect circle" technique and included projected anterior-to-posterior glenoid diameter, amount of posterior bone loss, and percentage of posterior bone loss. Intrarater reliability and inter-rater reliability were then determined by calculating intraclass correlation coefficients (ICCs). Results: Ten consecutive patients meeting the selection criteria were chosen for inclusion in this analysis. Average estimated bone loss for the cohort was 2.45 mm, and the mean estimated glenoid diameter of the involved shoulder was 28.82 mm. The average percentage of bone loss measured 8.54%. The ICC for interobserver reliability was 0.55 for the perfect circle diameter and 0.17 for the anterior bone loss measurement (poorly to moderately reliable). The ICC for intraobserver reliability was 0.69 for the perfect circle diameter and 0.71 for anterior bone loss (moderately reliable). Conclusions: The perfect circle technique for estimating anterior glenoid bone loss on magnetic resonance imaging was found to have moderate intrarater reliability; however, reliability between observers was found to be moderate to poor. Level of Evidence: Level IV, diagnostic case series.

Extracellular metallothionein as a therapeutic target in the early progression of type 1 diabetes.

Type 1 diabetes (T1D) is characterized by lymphocyte infiltration into the pancreatic islets of Langerhans, leading to the destruction of insulin-producing beta cells and uncontrolled hyperglycemia. In the nonobese diabetic (NOD) murine model of T1D, the onset of this infiltration starts several weeks before glucose dysregulation and overt diabetes. Recruitment of immune cells to the islets is mediated by several chemotactic cytokines, including CXCL10, while other cytokines, including SDF-1α, can confer protective effects. Global gene expression studies of the pancreas from prediabetic NOD mice and single-cell sequence analysis of human islets from prediabetic, autoantibody-positive patients showed an increased expression of metallothionein (MT), a small molecular weight, cysteine-rich metal-binding stress response protein. We have shown that beta cells can release MT into the extracellular environment, which can subsequently enhance the chemotactic response of Th1 cells to CXCL10 and interfere with the chemotactic response of Th2 cells to SDF-1α. These effects can be blocked in vitro with a monoclonal anti-MT antibody, clone UC1MT. When administered to NOD mice before the onset of diabetes, UC1MT significantly reduces the development of T1D. Manipulation of extracellular MT may be an important approach to preserving beta cell function and preventing the development of T1D.

Outcomes of Concomitant Glenohumeral Stabilization After Arthroscopic Rotator Cuff Repair in Military Patients Younger Than 40 Years.

Background: While concomitant rotator cuff and inferior labral tears are relatively uncommon in young civilians, military populations represent a unique opportunity to study this injury pattern. Purpose: To (1) evaluate the long-term outcomes after combined arthroscopic rotator cuff and inferior labral repair in military patients <40 years and (2) compare functional outcomes with those after isolated arthroscopic rotator cuff repair. Study Design: Cohort study; Level of evidence, 3. Methods: Military patients who underwent arthroscopic rotator cuff repair between January 2011 and December 2016 and had a minimum of 5-year follow-up data were included in this study. The patients were categorized into those who had undergone combined arthroscopic rotator cuff and inferior labral repair (RCIL cohort) and those who had isolated arthroscopic rotator cuff repair (ARCR cohort). Pre- and postoperative outcome measures-visual analog scale for pain, Single Assessment Numeric Evaluation, American Shoulder and Elbow Surgeons shoulder score, Rowe Instability Score, and range of motion-were compared between the groups. Results: A total of 50 shoulders (27 in the RCIL cohort and 23 in the ARCR cohort) were assessed. The RCIL and ARCR groups were similar in terms of age (mean, 33.19 years [range, 21-39 years] vs 35.39 years [range, 26-39 years], respectively) and sex (% male, 88.46% vs 82.61%, respectively). All patients were active-duty military at the time of surgery. The mean final follow-up was at 106.93 ± 16.66 months for the RCIL group and 105.70 ± 7.52 months for the ARCR group (P = .75). There were no differences in preoperative outcome scores between groups. Postoperatively, both groups experienced statistically significant improvements in all outcome scores (P < .0001 for all), and there were no significant group differences in any final postoperative outcome measures. At the final follow-up, 26 (96.30%) patients in the RCIL cohort and 20 (86.96%) in the ARCR cohort had returned to unrestricted active-duty military service (P = .3223). Conclusion: The study findings indicate that concomitant glenohumeral stabilization does not prevent worse outcomes after arthroscopic rotator cuff repair in this military cohort. Combined repair produced statistically and clinically significant improvements in outcome scores at the long-term follow-up, indicating that simultaneous repair of combined lesions was an appropriate treatment option in this patient population.

Establishing the Minimal Clinically Important Difference, Substantial Clinical Benefit, and Patient Acceptable Symptomatic State After Arthroscopic Posterior Labral Repair for Posterior Glenohumeral Instability.

BACKGROUND: Posterior glenohumeral instability is an increasingly recognized cause of shoulder pain and dysfunction among young, active populations. Outcomes after posterior stabilization procedures are commonly assessed using patient-reported outcome measures including the Single Assessment Numeric Evaluation (SANE), the Rowe instability score, the American Shoulder and Elbow Surgeons (ASES) score, and the visual analog scale (VAS) for pain. The clinical significance thresholds for these measures after arthroscopic posterior labral repair (aPLR), however, remain undefined. PURPOSE: We aimed to define the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) for the SANE, Rowe score, and ASES score as well as the VAS pain after aPLR. Additionally, we sought to determine preoperative factors predictive of reaching, as well as failing to reach, clinical significance. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: This study was a retrospective analysis of patient-reported outcome scores collected from patients who underwent aPLR between January 2011 and December 2018. To determine the clinically significant threshold that corresponded to achieving a meaningful outcome, the MCID, SCB, and PASS were calculated for the SANE, Rowe score, ASES score, and VAS pain utilizing either an anchor- or distribution-based method. Additionally, univariate and multivariate logistic regression analyses were performed to determine the factors associated with achieving, or not achieving, the MCID, SCB, and PASS. RESULTS: A total of 73 patients with a mean follow-up of 82.55 ± 24.20 months were available for final analysis. MCID, SCB, and PASS values for the VAS pain were 1.10, 6, and 3, respectively; for the ASES score were 7.8, 34, and 80, respectively; for the SANE were 10.15, 33, and 85, respectively; and for the Rowe score were 11.3, 60, and 90, respectively. To meet the MCID, male sex (odds ratio [OR], 1.1639; P = .0293) was found to be a positive predictor for the VAS pain, and a lower preoperative SANE score (OR, 0.9939; P = .0003) was found to be a negative predictor for the SANE. Dominant arm involvement was associated with lower odds of achieving the PASS for the ASES score (OR, 0.7834; P = .0259) and VAS pain (OR, 0.7887; P = .0436). Patients who reported a history of shoulder trauma were more likely to reach the PASS for the SANE (OR, 1.3501; P = .0089), Rowe score (OR, 1.3938; P = .0052), and VAS pain (OR, 1.3507; P = .0104) as well as the SCB for the ASES score (OR, 1.2642; P = .0469) and SANE (OR, 1.2554; P = .0444). A higher preoperative VAS pain score was associated with higher odds of achieving the SCB for both the VAS pain (OR, 1.1653; P = .0110) and Rowe score (OR, 1.1282; P = .0175). Lastly, concomitant biceps tenodesis was associated with greater odds of achieving the SCB for the ASES score (OR, 1.3490; P = .0130) and reaching the PASS for the SANE (OR, 1.3825; P = .0038) and Rowe score (OR, 1.4040; P = .0035). CONCLUSION: To our knowledge, this study is the first to define the MCID, SCB, and PASS for the ASES score, Rowe score, SANE, and VAS pain in patients undergoing aPLR. Furthermore, we found that patients who reported a history of shoulder trauma and those who underwent concomitant biceps tenodesis demonstrated a greater likelihood of achieving clinical significance. Dominant arm involvement was associated with lower odds of achieving clinical significance.

Subacromial Balloon Placement Demonstrates No Advantage Over Debridement in the Treatment of Massive Irreparable Rotator Cuff Tears: A Dual-Armed Systematic Review and Meta-analysis of Over 1000 Patients.

BACKGROUND: In recent years, the placement of a subacromial balloon (SAB) spacer has emerged as a treatment option for massive irreparable rotator cuff tears (MIRCTs); however, there is significant controversy regarding its utility in comparison with other surgical interventions. PURPOSE: To compare outcomes after SAB spacer placement versus arthroscopic debridement for MIRCTs. STUDY DESIGN: Dual-armed systematic review and meta-analysis (level IV evidence). METHODS: A literature search of PubMed (MEDLINE), Scopus, and CINAHL Complete databases for articles published before May 7, 2022, was conducted to identify patients with MIRCTs undergoing the 2 procedures. For the SAB arm, 14 of 449 studies were considered eligible for inclusion, while 14 of 272 studies were considered eligible for inclusion in the debridement arm. RESULTS: In total, 528 patients were eligible for inclusion in the SAB arm and 479 patients in the debridement arm, and 69.9% of patients undergoing SAB placement also underwent concomitant debridement. Decreases in the visual analog scale (VAS) pain score and increases in the Constant score were found to be significantly larger after debridement (-0.7 points [P < .001] and +5.5 points [P < .001], respectively), although the Patient Acceptable Symptom State for the VAS was not achieved after either procedure. Both SAB placement and debridement significantly improved range of motion in forward flexion/forward elevation, internal and external rotation, and abduction (P < .001). Rates of general complication were higher after debridement versus SAB placement (5.2% ± 5.6% vs 3.5% ± 6.3%, respectively; P < .001); however, there were no significant differences between SAB placement and debridement in rates of persistent symptoms requiring a reintervention (3.3% ± 6.2% vs 3.8% ± 7.3%, respectively; P = .252) or reoperation rates (5.1% ± 7.6% vs 4.8% ± 8.4%, respectively; P = .552). The mean time to conversion to reverse total shoulder arthroplasty was 11.0 versus 25.4 months, respectively, for the SAB versus debridement arm. CONCLUSION: While SAB placement was associated with acceptable postoperative outcomes in the treatment of MIRCTs, there was no clear benefit over debridement alone. Shorter operative times coupled with better postoperative outcomes and longer times to conversion to reverse total shoulder arthroplasty rendered debridement a more attractive option. While there may be a role for SAB placement in poor surgical candidates, there is burgeoning evidence to support debridement alone without SAB placement for the treatment of MIRCTs.

Measurement invariance of the Personality Inventory for the DSM-5 across U.S. East Asian, Southeast Asian, and White participants.

The Personality Inventory for the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition (PID-5) was developed as a measure of the traits included in the alternative model of personality disorders (AMPD) in Section III of the DSM. The PID-5 is composed of 25 scales measuring each trait in the AMPD across five domains: negative affectivity, detachment, disinhibition, antagonism, and psychoticism. Previous research suggests that there may be important differences in the expression of personality pathology across race and culture, particularly between people with eastern and western cultural heritages. The goal of the current research was to examine the measurement invariance of the PID-5 across these groups. In the current study, 865 young men and women who identified as White, East Asian, or Southeast Asian completed the PID-5 and international personality item pool (IPIP). On the domain level, a multigroup exploratory structural equation model found that the PID-5 had configural and metric invariance, but lacked complete scalar invariance. On an item level, all scales had configural invariance, one lacked metric invariance, and 11 of the 25 scales lacked scalar invariance across race. For the invariant scales, East and Southeast Asians tended to have higher mean scores than White participants. The PID-5 scales had similar relations with IPIP scales across groups. These results suggest that the PID-5 scales are measuring similar constructs across groups on a global, structural level, but that mean scores may represent different levels of latent personality pathology across groups. The PID-5 may be confidently used in these groups, but mean comparisons should be interpreted with caution. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neural-driven activation of 3D muscle within a finite element framework: exploring applications in healthy and neurodegenerative simulations.

This paper presents a novel computational framework for neural-driven finite element muscle models, with an application to amyotrophic lateral sclerosis (ALS). The multiscale neuromusculoskeletal (NMS) model incorporates physiologically accurate motor neurons, 3D muscle geometry, and muscle fiber recruitment. It successfully predicts healthy muscle force and tendon elongation and demonstrates a progressive decline in muscle force due to ALS, dropping from 203 N (healthy) to 155 N (120 days after ALS onset). This approach represents a preliminary step towards developing integrated neural and musculoskeletal simulations to enhance our understanding of neurodegenerative and neurodevelopmental conditions through predictive NMS models.

Concomitant Biceps Tenodesis Does Not Portend Inferior Outcomes After Anterior Glenohumeral Stabilization.

BACKGROUND: Military patients are known to suffer disproportionately high rates of glenohumeral instability as well as superior labrum anterior to posterior (SLAP) tears. Additionally, a concomitant SLAP tear is frequently observed in patients with anterior shoulder instability. Even though biceps tenodesis has been demonstrated to produce superior outcomes to SLAP repair in military patients with isolated SLAP lesions, no existing studies have reported on outcomes after simultaneous tenodesis and anterior labral repair in patients with co-existing abnormalities. PURPOSE: To evaluate outcomes after simultaneous arthroscopic-assisted subpectoral biceps tenodesis and anterior labral repair in military patients younger than 40 years. We also sought to compare these outcomes with those after repair of an isolated anterior labral tear. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study is a retrospective analysis of all military patients younger than 40 years from a single base who underwent arthroscopic anterior glenohumeral stabilization with or without concomitant biceps tenodesis between January 2010 and December 2019. Patients with glenoid bone loss of >13.5% were not eligible for inclusion. Outcome measures including the visual analog scale (VAS) for pain, the Single Assessment Numeric Evaluation (SANE), the American Shoulder and Elbow Surgeons (ASES) shoulder score, the Rowe instability score, and range of motion were administered preoperatively and postoperatively, and scores were compared between groups. RESULTS: A total of 82 patients met inclusion criteria for the study. All patients were active-duty service members at the time of surgery. The mean follow-up was 87.75 ± 27.05 months in the repair + tenodesis group and 94.07 ± 28.72 months in the isolated repair group (P = .3085). Patients who underwent repair + tenodesis had significantly worse preoperative VAS pain (6.85 ± 1.86 vs 5.02 ± 2.07, respectively; P < .001), ASES (51.78 ± 11.89 vs 62.43 ± 12.35, respectively; P = .0002), and Rowe (26.75 ± 7.81 vs 37.26 ± 14.91, respectively; P = .0002) scores than patients who underwent isolated repair. Both groups experienced significant improvements in outcome scores postoperatively (P < .0001 for all), and there were no statistically significant differences in postoperative outcome scores or range of motion between groups. There were no differences in the percentage of patients who achieved the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state for the VAS pain, SANE, ASES, and Rowe scores between groups. Overall, 37 of the 40 (92.50%) patients in the repair + tenodesis group and 40 of the 42 (95.24%) patients in the isolated repair group returned to unrestricted active-duty military service (P = .6045). In addition, 38 (95.00%) patients in the repair + tenodesis group and 40 (95.24%) patients in the isolated repair group returned to preinjury levels of sporting activity (P = .9600). There were no significant differences in the number of failures, revision surgical procedures, or patients discharged from the military between groups (P = .9421, P = .9400, and P = .6045, respectively). CONCLUSION: The findings of this study indicate that simultaneous biceps tenodesis and labral repair was a viable treatment option for the management of concomitant SLAP and anterior labral lesions in young, active military patients younger than 40 years.

Acromial Morphology Does Not Correlate with Age at Time of Rotator Cuff Tear: A Cross-Sectional Study.

Background: The purpose of this study was to determine if scapular anatomy differs between younger and older patients with atraumatic full-thickness supraspinatus tears. Methods: The critical shoulder angle, acromial index and lateral acromial angle were measured on standardized radiographs of two groups of patients who underwent arthroscopic repair of full-thickness degenerative supraspinatus tears. Group 1 included 61 patients under the age of 50 years while Group 2 included 45 patients over the age of 70 years. The mean critical shoulder angle, acromial index, and lateral acromial angle were then compared. Results: There was no significant difference between groups for the critical shoulder angle (p = .433), acromial index (p = .881) or lateral acromial angle (p = .263). Interobserver reliability for critical shoulder angle, acromial index, and lateral acromial angle was nearly perfect (interclass correlation coefficient 0.996, 0.996, 0.998, respectively). No significant correlation existed between age and critical shoulder angle (p = .309), acromial index (p = .484) or lateral acromial angle (p = .685). Discussion: While the critical shoulder angle and acromial index were found to be high and in the typical range for patients with rotator cuff tears in both groups, there were no significant differences in acromial morphology between Groups 1 and 2.

Increased deformations are dispensable for cell mechanoresponse in engineered bone analogs mimicking aging bone marrow.

Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in-part regulated by mesenchymal stem cells (MSCs) that respond to mechanical stimuli. Direct delivery of low intensity vibration (LIV) recovers MSC proliferation in senescence and simulated microgravity models, indicating that age-related reductions in mechanical signal delivery within bone marrow may contribute to declining bone mechanoresponse. To answer this question, we developed a 3D bone marrow analog that controls trabecular geometry, marrow mechanics and external stimuli. Validated finite element (FE) models were developed to quantify strain environment within hydrogels during LIV. Bone marrow analogs with gyroid-based trabeculae of bone volume fractions (BV/TV) corresponding to adult (25%) and aged (13%) mice were printed using polylactic acid (PLA). MSCs encapsulated in migration-permissive hydrogels within printed trabeculae showed robust cell populations on both PLA surface and hydrogel within a week. Following 14 days of LIV treatment (1g, 100 Hz, 1 hour/day), type-I collagen and F-actin were quantified for the cells in the hydrogel fraction. While LIV increased all measured outcomes, FE models predicted higher von Mises strains for the 13% BV/TV groups (0.2%) when compared to the 25% BV/TV group (0.1%). Despite increased strains, collagen-I and F-actin measures remained lower in the 13% BV/TV groups when compared to 25% BV/TV counterparts, indicating that cell response to LIV does not depend on hydrogel strains and that bone volume fraction (i.e. available bone surface) directly affects cell behavior in the hydrogel phase independent of the external stimuli. Overall, bone marrow analogs offer a robust and repeatable platform to study bone mechanobiology.

Long-Term Outcomes in Female Patients With Carpometacarpal Arthroplasty and Metacarpophalangeal Fusion Compared With the Unoperated Side or Carpometacarpal Arthroplasty.

PURPOSE: Patients with carpometacarpal (CMC) osteoarthritis (OA) often present with metacarpophalangeal (MP) hyperextension and/or thenar atrophy. This study hypothesizes that MP fusion (MPF) performed at the time of CMC arthroplasty (CMCA) for patients who have moderate-to-severe thenar atrophy, MP hyperextension >30°, or MP arthritis will have greater long-term pinch strength and improvements in the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score from preoperative values when compared with the unoperated side or those who had CMCA only. METHODS: This study involved a retrospective review of long-term results from patients who underwent either CMCA or CMCA/MPF. The QuickDASH score, the pain visual analog scale (VAS), and an average of three pinch readings from each thumb were measured on the Baseline pinch gauge and recorded with a correction for hand dominance in right-handed patients. RESULTS: Fifty-three female patients with 70 operated thumbs were included in the study. The mean age was 67.2 years. There were 29 CMCAs and 41CMCA/MPFs. The mean follow-up was 6.3 years (range 2-16.9 years). At the latest follow-up, the mean CMCA/MPF pinch strength (11.3 lbs) was significantly stronger than that of CMCA (8.0 lbs) and carpometacarpal osteoarthritis thumbs (8.9 lbs). There was no significant difference in pinch strength between patients who underwent a CMCA and CMCOA thumbs (8.0 lbs vs 8.9 lbs, respectively). Preoperative QuickDASH demonstrated worse function in the CMCA/MPF group (55.8 vs 36.5). At the latest follow-up, QuickDASH and VAS revealed similar values in both the CMCA/MPF (10.5 and 0.66) and CMCA (18.5 and 0.52) groups. CONCLUSION: Long-term results demonstrate stronger pinch and greater improvement in QuickDASH scores in patients who underwent CMCA/MPF compared with those who underwent a CMCA or untreated carpometacarpal osteoarthritis thumbs. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Surface, but Not Age, Impacts Lower Limb Joint Work during Walking and Stair Ascent.

Older adults often suffer an accidental fall when navigating challenging surfaces during common locomotor tasks, such as walking and ascending stairs. This study examined the effect of slick and uneven surfaces on lower limb joint work in older and younger adults while walking and ascending stairs. Fifteen young (18-25 years) and 12 older (>65 years) adults had stance phase positive limb and joint work quantified during walking and stair ascent tasks on a normal, slick, and uneven surface, which was then submitted to a two-way mixed model ANOVA for analysis. The stair ascent required greater limb, and hip, knee, and ankle work than walking (all p < 0.001), with participants producing greater hip and knee work during both the walk and stair ascent (both p < 0.001). Surface, but not age, impacted positive limb work. Participants increased limb (p < 0.001), hip (p = 0.010), and knee (p < 0.001) positive work when walking over the challenging surfaces, and increased hip (p = 0.015), knee (p < 0.001), and ankle (p = 0.010) work when ascending stairs with challenging surfaces. Traversing a challenging surface during both walking and stair ascent tasks required greater work production from the large proximal hip and knee musculature, which may increase the likelihood of an accidental fall in older adults.

Simultaneous Arthroscopic Rotator Cuff Repair and Glenoid Microfracture in Active-Duty Military Patients Younger Than 50 Years: Outcomes at Midterm Follow-up.

Background: While concomitant full-thickness rotator cuff tears and glenoid osteochondral defects are relatively uncommon in younger patients, military patients represent a unique opportunity to study this challenging injury pattern. Purpose/Hypothesis: To compare the outcomes of young, active-duty military patients who underwent isolated arthroscopic rotator cuff repair (ARCR) with those who underwent ARCR plus concurrent glenoid microfracture (ARCR+Mfx). It was hypothesized that ARCR+Mfx would produce significant improvements in patient-reported outcome measures. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective analysis of consecutive active-duty military patients from a single base who underwent ARCR for full-thickness rotator cuff tears between January 2012 and December 2020. All patients were <50 years and had minimum 2-year follow-up data. Patients who underwent ARCR+Mfx were compared with those who underwent isolated ARCR based on the visual analog scale (VAS) for pain, Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons (ASES) shoulder score, and range of motion. Results: A total of 88 patients met the inclusion criteria for this study: 28 underwent ARCR+Mfx and 60 underwent isolated ARCR. The mean final follow-up was 74.11 ± 33.57 months for the ARCR+Mfx group and 72.87 ± 11.46 months for the ARCR group (P = .80). There were no differences in baseline patient characteristics or preoperative outcome scores between groups. Postoperatively, both groups experienced statistically significant improvements in all outcome scores (P < .0001 for all). However, the ARCR+Mfx group had significantly worse VAS pain (1.89 ± 2.22 vs 1.03 ± 1.70; P = .05), SANE (85.46 ± 12.99 vs 91.93 ± 12.26; P = .03), and ASES (86.25 ± 14.14 vs 92.85 ± 12.57; P = .03) scores. At the final follow-up, 20 (71.43%) patients in the ARCR+Mfx group and 53 (88.33%) patients in the ARCR group were able to remain on unrestricted active-duty military service (P = .05). Conclusion: Concomitant ARCR+Mfx led to statistically and clinically significant improvements in patient-reported outcome measures at the midterm follow-up. However, patients who underwent ARCR+Mfx had significantly worse outcomes and were less likely to return to active-duty military service than those who underwent isolated ARCR. The study findings suggest that ARCR+Mfx may be a reasonable option for young, active patients who are not candidates for arthroplasty.

Risk Factors for Glenoid Bone Loss in the Setting of Posterior Glenohumeral Instability.

Background: Posterior instability has been reported to account for up to 24% of cases of shoulder instability in certain active populations. However, there is a paucity of data available regarding the risk factors associated with posterior glenoid bone loss. Purpose: To characterize the epidemiology of, and risk factors associated with, glenoid bone loss within a cohort of patients who underwent primary arthroscopic shoulder stabilization for isolated posterior-type glenohumeral instability. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This was a retrospective analysis of patients who underwent primary arthroscopic shoulder stabilization for posterior-type instability between January 2011 and December 2019. Preoperative magnetic resonance arthrograms were used to calculate posterior glenoid bone loss using a perfect circle technique. Patient characteristics and revision rates were obtained. Bone loss (both in millimeters and as a percentage) was compared between patients based on sex, age, arm dominance, sports participation, time to surgery, glenoid version, history of trauma, and number of anchors used for labral repair. Results: Included were 112 patients with a mean age of 28.66 ± 10.07 years; 91 patients (81.25%) were found to have measurable bone loss. The mean bone loss was 2.46 ± 1.68 mm (8.98% ± 6.12%). Significantly greater bone loss was found in athletes versus nonathletes (10.09% ± 6.86 vs 7.44% ± 4.56; P = .0232), female versus male patients (11.17% ± 6.53 vs 8.17% ± 5.80; P = .0212), and patients dominant arm involvement versus nondominant arm involvement (10.26% ± 5.63 vs 7.07% ± 6.38; P = .0064). Multivariate regression analysis identified dominant arm involvement as an independent risk factor for bone loss (P = .0033), and dominant arm involvement (P = .0024) and athlete status (P = .0133) as risk factors for bone loss >13.5%. At the conclusion of the study period, 7 patients had experienced recurrent instability (6.25%). Conclusion: The findings of this study are in alignment with existing data suggesting that posterior glenoid bone loss is highly prevalent in patients undergoing primary arthroscopic stabilization for posterior-type shoulder instability. Our results suggest that patients with dominant arm involvement are at risk for greater posterior glenoid bone loss. Athlete status and dominant arm involvement were identified as independent risk factors for bone loss >13.5%.

Epidemiology of shoulder dislocations presenting to United States emergency departments: An updated ten-year study.

BACKGROUND: Glenohumeral dislocation is a common injury that may predispose patients to chronic pain and instability. However, there is a paucity of current data available regarding the epidemiological trends of this injury. AIM: To provide an updated, comparative assessment of the epidemiology of shoulder dislocations presenting to emergency departments in the United States. We also sought to analyze patient demographic risk factors and consumer products associated with dislocation events. METHODS: Data were obtained from the national electronic injury surveillance system database for glenohumeral dislocations between 2012 and 2021. Incidence, age, sex, and injury characteristics were analyzed using weighted population statistics as well as incidence rates and 95% confidence intervals (CI). RESULTS: In total, an estimated 773039 shoulder dislocations (CI: 640598-905481) presented to emergency rooms across the United States during the study period. The annual incidence rate was 23.96 per 100000 persons and the average patient age at the time of injury was 37.1 years. Significantly more male patients sustained dislocations than female patients (537189, 69.5%, vs 235834, 30.5%, P < 0.001). With regard to associated consumer products, sports and recreation equipment were involved in the highest proportion of incidents (44.31%), followed by home structures and construction materials (21.22%), and home furnishings, fixtures, and accessories (21.21%). Regarding product sub-groups, stairs, ramps, landings, floors was cited in the greatest number of cases (131745). CONCLUSION: The national annual incidence rate of glenohumeral dislocations throughout the study period was approximately 23.92 per 100000 persons. Male adolescents sustained the highest proportion of dislocations, with a peak incidence in age group 15-20 years, predominantly secondary to participation in sporting and recreational activities. Conversely, women experienced a relatively consistent incidence of dislocation throughout their lifespan. After age 63, the incidence rate of dislocations in females was found to surpass that observed in males.

Infiltrating CD8+ T cells exacerbate Alzheimer's disease pathology in a 3D human neuroimmune axis model.

Brain infiltration of peripheral immune cells and their interactions with brain-resident cells may contribute to Alzheimer's disease (AD) pathology. To examine these interactions, in the present study we developed a three-dimensional human neuroimmune axis model comprising stem cell-derived neurons, astrocytes and microglia, together with peripheral immune cells. We observed an increase in the number of T cells (but not B cells) and monocytes selectively infiltrating into AD relative to control cultures. Infiltration of CD8+ T cells into AD cultures led to increased microglial activation, neuroinflammation and neurodegeneration. Using single-cell RNA-sequencing, we identified that infiltration of T cells into AD cultures led to induction of interferon-γ and neuroinflammatory pathways in glial cells. We found key roles for the C-X-C motif chemokine ligand 10 (CXCL10) and its receptor, CXCR3, in regulating T cell infiltration and neuronal damage in AD cultures. This human neuroimmune axis model is a useful tool to study the effects of peripheral immune cells in brain disease.

Outcomes Following Combined Posterior Labral and SLAP Repair in Military Patients Younger Than 35 Years.

BACKGROUND: Members of the military are known to experience disproportionately high rates of both glenohumeral instability and superior labrum anterior-posterior (SLAP) tears when compared with civilian populations. Although the outcomes after simultaneous repair of Bankart and SLAP lesions have been well described, there is a paucity of literature available regarding the operative management of posterior instability with concomitant superior labral pathology. PURPOSE: To compare outcomes of combined arthroscopic posterior labral and SLAP repair with those of isolated posterior labral repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All consecutive patients younger than 35 years who underwent arthroscopic posterior labral repair from January 2011 to December 2016 with a minimum follow-up of 5 years were identified. From this cohort of eligible patients, all individuals who had undergone combined SLAP and posterior labral repair (SLAP cohort) versus posterior labral repair alone (instability cohort) were then identified. Outcome measures including the visual analog scale score, Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons (ASES) score, Rowe instability score, and range of motion were collected pre- and postoperatively and scores were compared between groups. RESULTS: In total, 83 patients met the inclusion criteria for the study. All patients were active-duty military at the time of surgery. The mean follow-up was 93.79 ± 18.06 months in the instability group and 91.24 ± 18.02 months in the SLAP group (P = .5228). Preoperative SANE and ASES scores were significantly worse in the SLAP group. Both groups experienced statistically significant improvements in outcome scores postoperatively (P < .0001 for all), and there were no significant differences in any outcome scores or range of motion between groups. In total, 39 patients in the instability cohort and 37 in the SLAP cohort returned to preinjury levels of work (92.86% vs 90.24%, respectively; P = .7126), and 38 instability patients and 35 SLAP patients returned to preinjury levels of sporting activity (90.48% vs 85.37%, respectively; P = .5195). Two patients in the instability group and 4 patients in the SLAP group were medically discharged from the military (4.76% vs 9.76%; P = .4326), and 2 patients in each cohort had experienced treatment failure at the final follow-up (4.76% vs 4.88%; P > .9999). CONCLUSION: Combined posterior labral and SLAP repair led to statistically and clinically significant increases in outcome scores and high rates of return to active-duty military service that did not differ significantly from the results after isolated posterior labral repair. The results of this study indicate that simultaneous repair is a viable treatment option for the management of combined lesions in active-duty military patients <35 years of age.