SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.

Posttranslational modifications regulate the properties and abundance of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that mediate fast excitatory synaptic transmission and synaptic plasticity in the central nervous system. During long-term depression (LTD), protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues in the C-terminal tail of AMPA receptor GluA2 subunit, which is essential for GluA2 endocytosis and group I metabotropic glutamate receptor (mGluR)-dependent LTD. However, as a selective downstream effector of mGluRs, the mGluR-dependent PTP responsible for GluA2 tyrosine dephosphorylation remains elusive at Schaffer collateral (SC)-CA1 synapses. In the present study, we find that mGluR5 stimulation activates Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) by increasing phospho-Y542 levels in SHP2. Under steady-state conditions, SHP2 plays a protective role in stabilizing phospho-Y869 of GluA2 by directly interacting with GluA2 phosphorylated at Y869, without affecting GluA2 phospho-Y876 levels. Upon mGluR5 stimulation, SHP2 dephosphorylates GluA2 at Y869 and Y876, resulting in GluA2 endocytosis and mGluR-LTD. Our results establish SHP2 as a downstream effector of mGluR5 and indicate a dual action of SHP2 in regulating GluA2 tyrosine phosphorylation and function. Given the implications of mGluR5 and SHP2 in synaptic pathophysiology, we propose SHP2 as a promising therapeutic target for neurodevelopmental and autism spectrum disorders.

Postoperative Graft Volume Reduction Is Associated With Inferior Clinical Outcomes of Superior Capsule Reconstruction Using an Acellular Dermal Matrix Allograft.

PURPOSE: To evaluate whether postoperative graft volume reduction is associated with clinical outcomes after superior capsule reconstruction (SCR) and to identify factors related to graft volume change. METHODS: Between May 2018 and June 2021, patients who underwent SCR with acellular dermal matrix allograft for irreparable rotator cuff tear with a minimum 1-year follow-up and who had intact graft continuity in postoperative 6-month magnetic resonance imaging were retrospectively reviewed. The lateral half to the medial half of the graft volume ratio was defined as lateral half graft volume ratio. The difference between the preoperative and postoperative lateral half graft volume ratio was defined as lateral half graft volume change. Patients were divided into 2 groups: those with preserved graft volume (group I) and those with reduced graft volume (group II). Intergroup differences in clinical and radiological characteristics were analyzed. RESULTS: A total of 81 patients were included, with 47 (58.0%) in group I and 34 (42.0%) in group II. Group I showed significantly lower lateral half graft volume change (0.018 ± 0.064 vs 0.370 ± 0.177; P < .001) than group II. Group II showed significantly greater preoperative Hamada grade (1.3 ± 0.5 vs 2.2 ± 0.6, P < .001), an anteroposterior distance of the graft at the greater tuberosity (APGT) (30.3 ± 4.8 vs 35.2 ± 3.8, P < .001), and fatty infiltration of infraspinatus (2.3 ± 0.9 vs 3.1 ± 0.8, P < .001) and subscapularis (0.9 ± 0.9 vs 1.6 ± 1.3, P = .009) than group I. Group II had a significantly lower proportion of patients achieving MIC in Constant score than group I (70.2% vs 47.1%, P = .035). The Hamada grade, APGT, and fatty infiltration of infraspinatus and subscapularis were independent factors of graft volume change. CONCLUSIONS: Although SCR improved pain and shoulder function, postoperative graft volume reduction was related to a lower rate of minimal important change achievement in the Constant score compared with preserved graft volume. The preoperative Hamada grade, APGT, and fatty infiltration of infraspinatus and subscapularis were associated with graft volume reduction. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Deneddylating enzyme SENP8 regulates neuronal development.

Neddylation is a cellular process in which the neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) is conjugated to the lysine residue of target proteins via serial enzymatic cascades. Recently, it has been demonstrated that neddylation is required for synaptic clustering of metabotropic glutamate receptor 7 (mGlu7) and postsynaptic density protein 95 (PSD-95), and the inhibition of neddylation impairs neurite outgrowth and excitatory synaptic maturation. Similar to the balanced role of deubiquitylating enzymes (DUBs) in the ubiquitination process, we hypothesized that deneddylating enzymes can regulate neuronal development by counteracting the process of neddylation. We find that the SUMO peptidase family member, NEDD8 specific (SENP8) acts as a key neuronal deneddylase targeting the global neuronal substrates in primary rat cultured neurons. We demonstrate that SENP8 expression levels are developmentally regulated, peaking around the first postnatal week and gradually diminishing in mature brain and neurons. We find that SENP8 negatively regulates neurite outgrowth through multiple pathways, including actin dynamics, Wnt/ß-catenin signaling, and autophagic processes. Alterations in neurite outgrowth by SENP8 subsequently result in the impairment of excitatory synapse maturation. Our data indicate that SENP8 plays an essential role in neuronal development and is a promising therapeutic target for neurodevelopmental disorders.

Arthroscopic-Assisted Double-Bundle Coracoclavicular Ligament Reconstruction Using Cortical Fixation Buttons With Suture Tape Provides Superior Vertical Stability Than the Single-Bundle Reconstruction for Acute Acromioclavicular Joint Dislocation.

PURPOSE: This study aimed to compare clinical and radiologic outcomes between single- and double-bundle arthroscopic-assisted coracoclavicular (CC) ligament reconstruction using cortical fixation buttons with suture tapes for acute acromioclavicular (AC) joint dislocation. METHODS: Patients who underwent arthroscopic-assisted CC ligament reconstruction using cortical fixation buttons with suture tapes for acute AC joint dislocation from July 2014 to March 2019 were identified. This study included patients treated for acute AC joint dislocation within 2 weeks after an injury, with a Rockwood classification of III or V and at least 2 years of follow-up. Patients were divided into 2 groups based on the reconstruction technique: group I (single-bundle technique) and group II (double-bundle technique). The clinical outcomes were compared using the American Shoulder Elbow Surgeons (ASES) score, Constant score, and visual analog scale for pain score between the 2 groups. On the plain radiograph, the CC interval ratio (CCIR) was measured to evaluate maintenance of CC interval fixation. Postoperative complications, including reduction failure, were also documented. RESULTS: Fifty-eight patients (26 in group I, 32 in group II) were enrolled. There were no significant differences in CCIR between the 2 groups preoperatively and 3 months postoperatively. However, the CCIR of group I was significantly greater than that of group II 6 months postoperatively (group I: 160.5% ± 48.5%, group II: 125.4% ± 38.9% at 6 months postoperatively, P = .01; group I: 164.0% ± 57.3%, group II: 123.2% ± 35.9% at the last visit, P = .01). Despite radiologic differences, the clinical outcomes demonstrated no significant differences between 2 the groups (ASES score: 93.5 ± 5.2 in group I, 94.4 ± 4.5 in group II, P = .54; Constant score: 92.9 ± 5.3 in group I, 94.8 ± 4.3 in group II, P = .16). Reduction failure occurred in 4 patients (15.3%) in group I and in 1 patient (3.2%) in group II (P = .16). CONCLUSIONS: Arthroscopic-assisted double-bundle CC ligament reconstruction using cortical fixation buttons with suture tapes provided superior vertical stability than the single-bundle technique. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Satisfactory functional and structural outcomes of anterior cable reconstruction using the proximal biceps tendon for large retracted rotator cuff tears.

PURPOSE: Large retracted anterior L-shaped tear characterized by a retracted supraspinatus tendon to the glenoid level combined with a relatively preserved infraspinatus tendon is one of the challenging tear patterns in achieving complete repair to the anatomic footprint. The purpose of this study was to evaluate clinical outcomes and tendon integrity of rotator cuff repair combined with anterior cable reconstruction using the proximal biceps tendon in patients with large retracted anterior L-shaped rotator cuff tear. METHODS: This study prospectively enrolled patients who underwent arthroscopic anterior cable reconstruction using the proximal biceps tendon for large retracted anterior L-shaped rotator cuff tears between 2018 and 2020 with a minimum 2-year follow-up. The anterior portion of the rotator cable was reconstructed using tenotomized proximal biceps tendon fixed with two suture anchors at the footprint. The retracted supraspinatus tendon was repaired on the biceps tendon without undue tension. The proximal portion of the infraspinatus tendon was repaired with the biceps tendon-supraspinatus tendon complex. Clinical outcomes was assessed during the follow-up period. Tendon integrity and retear size were evaluated by postoperative MRI. RESULTS: A total of 32 consecutive patients were included. The ASES score was significantly improved from 66.6 ± 16.6 preoperatively to 94.1 ± 6.1 postoperatively (P < 0.001), and the VAS for pain was significantly relieved from 2.8 ± 1.9 preoperatively to 0.5 ± 0.4 postoperatively (P < 0.001). All patients were satisfied postoperatively regardless of tendon integrity (P = 0.015). Postoperative ROM was increased continuously during the follow-up period (P < 0.001). The Popeye sign was found in 4 patients (12.5%). Six patients (18.7%) had rotator cuff retears. However, the ASES score of patients with retear was significantly improved from 72.8 ± 13.3 preoperatively to 91.1 ± 6.7 postoperatively (P < 0.001). Relative changes in the retear size compared with the primary tear size were -56.8 ± 14.4% for the anteroposterior diameter and - 70.6 ± 6.1% for the mediolateral diameter. CONCLUSIONS: Rotator cuff repair combined with anterior cable reconstruction using the proximal biceps tendon provided satisfactory clinical and radiological outcomes for large retracted anterior L-shaped tears. Anterior cable reconstruction using the proximal biceps tendon is a sound surgical option for the patients with large retracted anterior rotator cuff tear. LEVEL OF EVIDENCE: IV.

Pathogenic GRM7 Mutations Associated with Neurodevelopmental Disorders Impair Axon Outgrowth and Presynaptic Terminal Development.

Metabotropic glutamate receptor 7 (mGlu7) is an inhibitory heterotrimeric G-protein-coupled receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals in the mammalian central nervous system. Recent studies have shown that rare mutations in glutamate receptors and synaptic scaffold proteins are associated with neurodevelopmental disorders (NDDs). However, the role of presynaptic mGlu7 in the pathogenesis of NDDs remains largely unknown. Recent whole-exome sequencing (WES) studies in families with NDDs have revealed that several missense mutations (c.1865G>A:p.R622Q; c.461T>C:p.I154T; c.1972C>T:p.R658W and c.2024C>A:p.T675K) or a nonsense mutation (c.1757G>A:p.W586X) in the GRM7 gene may be linked to NDDs. In the present study, we investigated the mechanistic links between GRM7 point mutations and NDD pathology. We find that the pathogenic GRM7 I154T and R658W/T675K mutations lead to the degradation of the mGlu7 protein. In particular, the GRM7 R658W/T675K mutation results in a lack of surface mGlu7 expression in heterologous cells and cultured neurons isolated from male and female rat embryos. We demonstrate that the expression of mGlu7 variants or exposure to mGlu7 antagonists impairs axon outgrowth through the mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling pathway during early neuronal development, which subsequently leads to a decrease in the number of presynaptic terminals in mature neurons. Treatment with an mGlu7 agonist restores the pathologic phenotypes caused by mGlu7 I154T but not by mGlu7 R658W/T675K because of its lack of neuronal surface expression. These findings provide evidence that stable neuronal surface expression of mGlu7 is essential for neural development and that mGlu7 is a promising therapeutic target for NDDs.SIGNIFICANCE STATEMENT Neurodevelopmental disorders (NDDs) affect brain development and function by multiple etiologies. Metabotropic glutamate receptor 7 (mGlu7) is a receptor that controls excitatory neurotransmission and synaptic plasticity. Since accumulating evidence indicates that the GRM7 gene locus is associated with NDD risk, we analyzed the functional effects of human GRM7 variants identified in patients with NDDs. We demonstrate that stable neuronal surface expression of mGlu7 is essential for axon outgrowth and presynaptic terminal development in neurons. We found that mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling and subsequent cytoskeletal dynamics are defective because of the degradation of mGlu7 variants. Finally, we show that the defects caused by mGlu7 I154T can be reversed by agonists, providing the rationale for proposing mGlu7 as a potential therapeutic target for NDDs.

Superior Capsular Reconstruction Using Acellular Dermal Allograft Combined With Remaining Rotator Cuff Augmentation Improved Shoulder Pain and Function at 1 Year After The Surgery.

PURPOSE: The purpose of this study is to report structural integrity and clinical outcomes of superior capsular reconstruction (SCR) using a 4- to 5-mm acellular dermal allograft combined with augmentation of the remaining rotator cuff to the graft. METHODS: We prospectively recruited 21 patients with symptomatic irreparable rotator cuff tear who required SCR. At least 6 months after the SCR, we evaluated each patient's graft healing by magnetic resonance imaging (MRI). We also assessed the range of motion (ROM), strength for forward flexion and external rotation, visual analog scale for pain (PVAS), American Shoulder and Elbow Surgeon (ASES) score, and Constant score. At minimum of 1 year after the surgery, we evaluated the number of patients with minimal clinically important differences (MCIDs) for each score to compare patients with healed and unhealed grafts. RESULTS: Postoperative MRI showed the grafts intact in 14 patients (66.7%). Among 7 patients with unhealed grafts, tears were observed in 3 patients (42.9%) on the glenoid side, 3 (42.9%) on the humeral side, and 1 (14.3%) on both sides. PVAS, ASES score, and the Constant score improved after surgery (4.0 to 0.7 for PVAS [P < .001], 55.5 to 87.0 for ASES score [P < .001], and 56.0 to 65.9 for Constant score [P = .007]). However, there were no differences in postoperative ROM and muscle strength compared to preoperative measurements. MCIDs were reached in 90.5% of patients (n = 19) for the PVAS and in 71.4% of patients (n = 15) for the ASES score. Only 33.3% of patients (n = 7) obtained MCIDs for the Constant score, and none of the patients with a graft tear obtained MCIDs in the Constant score (P = .047). CONCLUSION: The graft complete healing rate was 66.7%, although pain relief and functional improvement were satisfactory regardless of graft structural integrity. However, muscle strength recovery was not optimal until 1 year after surgery. LEVEL OF EVIDENCE: Level IV; case series.

Tear pattern after superior capsular reconstruction using an acellular dermal matrix allograft.

BACKGROUND: The healing rate and tear pattern of grafts in superior capsular reconstruction (SCR) using acellular dermal matrix (ADM) allograft are poorly understood, and clinical results based on the graft status remain controversial. METHODS: Fifty-one consecutive patients undergoing arthroscopic SCR with ADM between October 2017 and February 2020 were enrolled. Range of motion, strength, and the visual analog scale pain (PVAS) score, American Shoulder and Elbow Surgeons (ASES) score, and Constant score were evaluated preoperatively and at the last follow-up. Postoperative magnetic resonance imaging was performed in all patients and was obtained at least 6 months (mean, 8.9 ± 3.6 months) after surgery. The graft tear status was analyzed on magnetic resonance imaging, and the numbers of patients who achieved the minimal clinically important difference and patient acceptable symptomatic state were analyzed to determine the differences in outcome according to graft tear status. RESULTS: The range of motion and clinical results improved at a minimum of 1 year (mean, 18 ± 5.4 months), whereas strength in forward flexion and external rotation did not (P = .676 and P = .995, respectively). The graft was intact in 36 of 51 patients (70.6%), 9 patients (17.6%) showed an incomplete graft tear with maintained continuity (partial graft rupture at 1 anchor on either the glenoid or humeral side), and 6 patients (11.8%) showed complete graft rupture (5 on the glenoid side and 1 on the humeral side). In cases with a tear (either incomplete or complete), the odds of achieving the minimal clinically important difference for the PVAS score (P = .047) and ASES score (P = .020) was significantly lower than that of the intact graft. However, when the continuity of the graft was maintained, even in cases with a partial tear, patients who reached the patient acceptable symptomatic state showed significantly higher odds for the PVAS score and trends for the ASES score. CONCLUSION: After SCR using ADM, the graft status could be classified as intact, an incomplete graft tear (where the continuity between the glenoid and humerus was maintained), or an complete tear. When the graft continuity was maintained, even in incomplete graft tears, patients were generally satisfied with postoperative pain and function at 1 year following SCR.

Colorimetric Sensor Based on Hydroxypropyl Cellulose for Wide Temperature Sensing Range.

Recently, temperature monitoring with practical colorimetric sensors has been highlighted because they can directly visualize the temperature of surfaces without any power sources or electrical transducing systems. Accordingly, several colorimetric sensors that convert the temperature change into visible color alteration through various physical and chemical mechanisms have been proposed. However, the colorimetric temperature sensors that can be used at subzero temperatures and detect a wide range of temperatures have not been sufficiently explored. Here, we present a colorimetric sensory system that can detect and visualize a wide range of temperatures, even at a temperature below 0 °C. This system was developed with easily affordable materials via a simple fabrication method. The sensory system is mainly fabricated using hydroxypropyl cellulose (HPC) and ethylene glycol as the coolant. In this system, HPC can self-assemble into a temperature-responsive cholesteric liquid crystalline mesophase, and ethylene glycol can prevent the mesophase from freezing at low temperatures. The colorimetric sensory system can quantitatively visualize the temperature and show repeatability in the temperature change from -20 to 25 °C. This simple and reliable sensory system has great potential as a temperature-monitoring system for structures exposed to real environments.

GPU-Accelerated PD-IPM for Real-Time Model Predictive Control in Integrated Missile Guidance and Control Systems.

This paper addresses the problem of real-time model predictive control (MPC) in the integrated guidance and control (IGC) of missile systems. When the primal-dual interior point method (PD-IPM), which is a convex optimization method, is used as an optimization solution for the MPC, the real-time performance of PD-IPM degenerates due to the elevated computation time in checking the Karush-Kuhn-Tucker (KKT) conditions in PD-IPM. This paper proposes a graphics processing unit (GPU)-based method to parallelize and accelerate PD-IPM for real-time MPC. The real-time performance of the proposed method was tested and analyzed on a widely-used embedded system. The comparison results with the conventional PD-IPM and other methods showed that the proposed method improved the real-time performance by reducing the computation time significantly.

Three-Dimensional Perovskite Nanopixels for Ultrahigh-Resolution Color Displays and Multilevel Anticounterfeiting.

Hybrid perovskites are emerging as a promising, high-performance luminescent material; however, the technological challenges associated with generating high-resolution, free-form perovskite structures remain unresolved, limiting innovation in optoelectronic devices. Here, we report nanoscale three-dimensional (3D) printing of colored perovskite pixels with programmed dimensions, placements, and emission characteristics. Notably, a meniscus comprising femtoliters of ink is used to guide a highly confined, out-of-plane crystallization process, which generates 3D red, green, and blue (RGB) perovskite nanopixels with ultrahigh integration density. We show that the 3D form of these nanopixels enhances their emission brightness without sacrificing their lateral resolution, thereby enabling the fabrication of high-resolution displays with improved brightness. Furthermore, 3D pixels can store and encode additional information into their vertical heights, providing multilevel security against counterfeiting. The proof-of-concept experiments demonstrate the potential of 3D printing to become a platform for the manufacture of smart, high-performance photonic devices without design restrictions.

Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.

The dentate gyrus (DG) in the hippocampus may play key roles in remembering distinct episodes through pattern separation, which may be subserved by the sparse firing properties of granule cells (GCs) in the DG. Low intrinsic excitability is characteristic of mature GCs, but ion channel mechanisms are not fully understood. Here, we investigated ionic channel mechanisms for firing frequency regulation in hippocampal GCs using male and female mice, and identified Kv4.1 as a key player. Immunofluorescence analysis showed that Kv4.1 was preferentially expressed in the DG, and its expression level determined by Western blot analysis was higher at 8-week than 3-week-old mice, suggesting a developmental regulation of Kv4.1 expression. With respect to firing frequency, GCs are categorized into two distinctive groups: low-frequency (LF) and high-frequency (HF) firing GCs. Input resistance (Rin) of most LF-GCs is lower than 200 MΩ, suggesting that LF-GCs are fully mature GCs. Kv4.1 channel inhibition by intracellular perfusion of Kv4.1 antibody increased firing rates and gain of the input-output relationship selectively in LF-GCs with no significant effect on resting membrane potential and Rin, but had no effect in HF-GCs. Importantly, mature GCs from mice depleted of Kv4.1 transcripts in the DG showed increased firing frequency, and these mice showed an impairment in contextual discrimination task. Our findings suggest that Kv4.1 expression occurring at late stage of GC maturation is essential for low excitability of DG networks and thereby contributes to pattern separation.SIGNIFICANCE STATEMENT The sparse activity of dentate granule cells (GCs), which is essential for pattern separation, is supported by high inhibitory inputs and low intrinsic excitability of GCs. Low excitability of GCs is thought to be attributable to a high K+ conductance at resting membrane potentials, but this study identifies Kv4.1, a depolarization-activated K+ channel, as a key ion channel that regulates firing of GCs without affecting resting membrane potentials. Kv4.1 expression is developmentally regulated and Kv4.1 currents are detected only in mature GCs that show low-frequency firing, but not in less mature high-frequency firing GCs. Furthermore, mice depleted of Kv4.1 transcripts in the dentate gyrus show impaired pattern separation, suggesting that Kv4.1 is crucial for sparse coding and pattern separation.

N-linked glycosylation of the mGlu7 receptor regulates the forward trafficking and transsynaptic interaction with Elfn1.

Metabotropic glutamate receptor 7 (mGlu7) regulates neurotransmitter release at the presynaptic active zone in the mammalian brain. The regulation of mGlu7 trafficking into and out of the plasma membrane by binding proteins within the C-terminal region of mGlu7 governs the bidirectional synaptic plasticity. However, the functional importance of the extracellular domain of mGlu7 has not yet been characterized. N-glycosylation is an abundant posttranslational modification that plays crucial roles in protein folding and forward trafficking, but the role of N-glycosylation in mGlu7 function remains unknown. In this study, we find that mGlu7 is N-glycosylated at four asparagine residues in heterologous cells and rat cultured neurons. We demonstrate that N-glycosylation is essential for forward transport and surface expression of mGlu7. Deglycosylated mGlu7 is retained in the ER, obstructing expression on the cell surface, and is degraded through the autophagolysosomal degradation pathway. In addition, we identify the binding domain of mGlu7 to Elfn1, a transsynaptic adhesion protein. We find that N-glycosylation of mGlu7 promotes its interaction with Elfn1, thereby enabling proper localization and stable surface expression of mGlu7 at the presynaptic active zone. These findings provide evidence that N-glycans act to modulate the surface expression, stability, and function of mGlu7.

Greater Tuberosity Bone Mineral Density and Rotator Cuff Tear Size Are Independent Factors Associated With Cutting-Through in Arthroscopic Suture-Bridge Rotator Cuff Repair.

PURPOSE: To evaluate the correlation between cutting-through at the greater tuberosity (GT) in arthroscopic suture-bridge rotator cuff repair and the bone mineral density (BMD) of the lumbar spine, hip, and ipsilateral GT of the proximal humerus and to evaluate factors and clinical outcomes related to cutting-through. METHODS: This study prospectively enrolled patients who underwent arthroscopic knotted suture-bridge rotator cuff repair for full-thickness rotator cuff tears between June 2014 and October 2015 and who had undergone dual-energy X-ray absorptiometry cans within 1 month before surgery with a minimum 2-year follow-up. Cutting-through was defined as the occurrence of cortical breakage of the GT just medial to the lateral knotless anchor hole due to the tension of the sutures from the medial anchor, and it was assessed. Clinical and radiologic data were analyzed. Univariate and regression analyses were performed to evaluate factors related to cutting-through. RESULTS: A total of 78 patients were analyzed. Patients were divided into 2 groups: patients who had cutting-through (46, group I) and patients who did not (32, group II). In an analysis of lumbar spine, hip, and GT BMD, GT BMD was the most effective for predicting cutting-through (area under the receiver operating characteristic curve = 0.94, 95% confidence interval 0.89-0.99). GT BMD (P < .001) and tear size (P = .004) were independent factors for cutting-through. Although a significant difference was found between the 2 groups in terms of age, sex, lumbar spine and hip BMD, fatty infiltration of the supraspinatus and infraspinatus, and atrophy of the supraspinatus, these variables were not independent factors. Clinical and structural outcomes showed no significant difference between the 2 groups, and anchor failure was not identified intraoperatively. CONCLUSIONS: GT BMD and rotator cuff tear size are independent factors associated with cutting-through at the GT. A dual-energy X-ray absorptiometry scan of the proximal humerus is useful for predicting bone quality before arthroscopic suture-bridge rotator cuff repair. LEVEL OF EVIDENCE: Level II, Prospective cohort study.

Clinical differences between patients with early and late revision surgery for symptomatic failed arthroscopic rotator cuff repair.

PURPOSE: Time ranges of revision rotator cuff surgeries after arthroscopic repair are highly variable. However, the cause and clinical relevance of the different timings of revision surgeries have not been analyzed. The purpose of this study was to evaluate the clinical manifestations of patients who required revision surgeries at early and late periods after failed arthroscopic rotator cuff repair, and to identify clinical and radiological differences related to the timing of revision surgery. METHODS: Sixty patients who underwent revision surgery due to symptomatic failed rotator cuff repair after arthroscopic repair were included. Patients were divided into two groups: patients who underwent revision surgeries within 1 year postoperatively (21 patients, group I) and patients who underwent revision surgeries more than 1 year postoperatively (39 patients, group II). Clinical and radiological characteristics were compared between the two groups before primary and revision surgery. RESULTS: VAS for pain (5.9 ± 1.9 in group I, 3.9 ± 1.4 in group II, P < 0.001) and Constant score (50.7 ± 9.9 in group I, 60.4 ± 8.9 in group II, P < 0.001) at the time of revision surgery were significantly different between the two groups. In group II, isometric muscle strength of forward flexion (74.1 ± 21.1 to 63.9 ± 15.1, P = 0.020) and external rotation (73.0 ± 23.5 to 61.2 ± 15.0, P = 0.032) were significantly deteriorated after primary surgery, even with significant improvement of pain and shoulder function (VAS: 5.7 ± 1.9 to 3.9 ± 1.4, P < 0.001; Constant score: 50.3 ± 11.0 to 60.4 ± 8.9, P < 0.001). On postoperative MRI, re-tear at the tendon-bone interface on the greater tuberosity occurred significantly more in group I (81.0%) than group II (51.3%, P = 0.024). Incidence of full-thickness tear of the subscapularis tendon was significantly different between the two groups (42.9% in group I, 12.8% in group II, P = 0.012). CONCLUSION: Patients who had early revision surgeries had significantly worse clinical outcomes after primary surgery than patients who had late revision surgeries. Healing failure at the tendon-bone interface on the greater tuberosity and re-tear combined with full-thickness tear of subscapularis tendon were related to early revision. Conversely, patients of the late revision group had muscle weakness that considerably impacted daily activities, even with improved pain and shoulder function. LEVEL OF EVIDENCE: III.

Metals by Micro-Scale Additive Manufacturing: Comparison of Microstructure and Mechanical Properties.

Many emerging applications in microscale engineering rely on the fabrication of 3D architectures in inorganic materials. Small-scale additive manufacturing (AM) aspires to provide flexible and facile access to these geometries. Yet, the synthesis of device-grade inorganic materials is still a key challenge toward the implementation of AM in microfabrication. Here, a comprehensive overview of the microstructural and mechanical properties of metals fabricated by most state-of-the-art AM methods that offer a spatial resolution ≤10 µm is presented. Standardized sets of samples are studied by cross-sectional electron microscopy, nanoindentation, and microcompression. It is shown that current microscale AM techniques synthesize metals with a wide range of microstructures and elastic and plastic properties, including materials of dense and crystalline microstructure with excellent mechanical properties that compare well to those of thin-film nanocrystalline materials. The large variation in materials' performance can be related to the individual microstructure, which in turn is coupled to the various physico-chemical principles exploited by the different printing methods. The study provides practical guidelines for users of small-scale additive methods and establishes a baseline for the future optimization of the properties of printed metallic objects-a significant step toward the potential establishment of AM techniques in microfabrication.

Drop impact on hot plates: contact times, lift-off and the lamella rupture.

When a liquid drop impacts on a heated substrate, it can remain deposited, or violently boil in contact, or lift off with or without ever touching the surface. The latter is known as the Leidenfrost effect. The duration and area of the liquid-substrate contact are highly relevant for the heat transfer, as well as other effects such as corrosion. However, most experimental studies rely on side view imaging to determine contact times, and those are often mixed with the time until the drop lifts off from the substrate. Here, we develop and validate a reliable method of contact time determination using high-speed X-ray imaging and total internal reflection imaging. We exemplarily compare contact and lift-off times on flat silicon and sapphire substrates. We show that drops can rebound even without formation of a complete vapor layer, with a wide range of lift-off times. On sapphire, we find a local minimum of lift-off times that is much shorter than expected from capillary rebound in the comparatively low-temperature regime of transition boiling/thermal atomization. We elucidate the underlying mechanism related to spontaneous rupture of the lamella and receding of the contact area.

Factors Related to Symptomatic Failed Rotator Cuff Repair Leading to Revision Surgeries After Primary Arthroscopic Surgery.

PURPOSE: To evaluate the clinical characteristics of patients with symptomatic failed rotator cuff repair who required revision surgeries and to identify clinical and radiologic factors related to the need for revision surgery. METHODS: Ninety-eight patients who were diagnosed with rotator cuff retear within 2 years after primary arthroscopic surgery were included. Patients were divided into 2 groups: patients who underwent revision surgery within 2 years postoperatively (44 patients, group I) and patients who did not require additional treatment due to minimal discomfort during the same period (54 patients, group II). Demographic and radiographic factors related to cuff healing were analyzed. Univariate and multivariate analyses were performed to evaluate factors related to revision surgery. RESULTS: Group I showed significantly inferior clinical outcomes at the time of revision compared to group II (American Shoulder and Elbow Surgeons score; 54.0 ± 12.1 vs 86.5 ± 12.2, Constant score; 65.2 ± 10.8 vs 84.0 ± 11.4, P < .001). Total cholesterol level (210.2 ± 40.0 vs 189.7 ± 39.1, P = .012), low-density lipoprotein level (130.7 ± 28.7 vs 115.5 ± 26.9, P = .008), and fatty infiltration of the infraspinatus (20.5% vs 3.7%, P = .011) were significantly greater in group I than in group II. On postoperative magnetic resonance imaging, retear of the infraspinatus tendon occurred significantly more frequently in group I (81.8%) than in group II (37.0%, P < .001). In group I, relative changes in anteroposterior (AP) (19.2 ± 37.8) and mediolateral retear size (29.6 ± 90.7) were significantly greater than in group II (AP; -39.5 ± 19.2, mediolateral; -29.2 ± 26.8, P < .001). Relative change in AP retear size was the most powerful independent predictor of symptomatic failed rotator cuff repair (odds ratio 1.19, confidence interval 1.08-1.31, P < .001). CONCLUSIONS: Preoperative serum total cholesterol level, low-density lipoprotein levels, and fatty infiltration of the infraspinatus were significantly related to symptomatic failed rotator cuff repair. Relative change in AP retear size was the most powerful independent predictor of symptomatic failed rotator cuff repair. LEVEL OF EVIDENCE: Level III, Case-control study.

Dexmedetomidine combined with interscalene brachial plexus block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair.

PURPOSE: Interscalene brachial plexus block (ISB) is one of the most commonly used regional blocks in relieving postoperative pain after arthroscopic rotator cuff repair. Dexmedetomidine (DEX) is an alpha 2 agonist that can enhance the effect of regional blocks. The aim of this study was to compare the effects of DEX combined with ISB with ISB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. METHODS: Fifty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single center, double-blinded randomized controlled trial study. Twenty-five patients were randomly allocated to group 1 and received ultrasound-guided ISB using a mixture of 1 ml (100 µg) of DEX and 8 ml of 0.75% ropivacaine preemptively. The other 25 patients were allocated to group 2 and underwent ultrasound-guided ISB alone using a mixture of 1 ml of normal saline and 8 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were checked within 48 h postoperatively. The plasma interleukin (IL)-6, -8, -1ß, cortisol, and substance P levels were also measured within 48 h, postoperatively. RESULTS: Group 1 showed a significantly lower mean VAS score and a significantly higher mean SAT score than group 2 at 1, 3, 6, 12, and 18 h postoperatively. Compared with group 2, group 1 showed a significantly lower mean plasma IL-6 level at 1, 6, 12, and 48 h postoperatively and a significantly lower mean IL-8 level at 1, 6, 12, 24, and 48 h postoperatively. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (12.7 h > 9.4 h, p = 0.006). CONCLUSIONS: Ultrasound-guided ISB with DEX in arthroscopic rotator cuff repair led to a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h postoperatively than ISB alone. In addition, ISB with DEX showed lower mean plasma IL-6 and IL-8 levels than ISB alone within 48 h postoperatively, with delayed rebound pain. LEVEL OF EVIDENCE: I. TRIAL REGISTRATION: 2013-112, ClinicalTrials.gov Identifier: NCT02766556.

Biosynthetically Inspired Syntheses of Secu'amamine A and Fluvirosaones A and B.

Presented here is a concise synthesis of secu'amamine A, and fluvirosaones A and B from readily available allosecurinine and viroallosecurinine. The key C2-enamine derivative of (viro)allosecurinine, the presumed biosynthetic precursors of these natural products, was accessed, for the first time, by a VO(acac)2 -mediated regioselective Polonovski reaction. Formal hydration and 1,2-amine shift of this pluripotent enamine compound afforded secu'amamine A. Formal oxidative [3+2] cycloaddition reaction between this enamine and TMS-substituted methallyl iodide reagent paved the way to the precursors of fluvirosaones A and B. The relative stereochemistry at the C2 position of these advanced intermediates governs the fate of 1,2-amine shift leading to fluvirosaones A and B. The syntheses of potential biosynthetic precursors and investigations of their chemical reactivities have provided insights regarding the biogenesis of these natural products.