Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated Ca2+ dynamics.

The pancreatic islet is surrounded by ECM that provides both biochemical and mechanical cues to the islet ß-cell to regulate cell survival and insulin secretion. Changes in ECM composition and mechanical properties drive ß-cell dysfunction in many pancreatic diseases. While several studies have characterized changes in islet insulin secretion with changes in substrate stiffness, little is known about the mechanotransduction signaling driving altered islet function in response to mechanical cues. We hypothesized that increasing matrix stiffness will lead to insulin secretion dysfunction by opening the mechanosensitive ion channel Piezo1 and disrupting intracellular Ca2+ dynamics in mouse and human islets. To test our hypothesis, mouse and human cadaveric islets were encapsulated in a biomimetic reverse thermal gel (RTG) scaffold with tailorable stiffness that allows formation of islet focal adhesions with the scaffold and activation of Piezo1 in 3D. Our results indicate that increased scaffold stiffness causes insulin secretion dysfunction mediated by increases in Ca2+ influx and altered Ca2+ dynamics via opening of the mechanosensitive Piezo1 channel. Additionally, inhibition of Piezo1 rescued glucose-stimulated insulin secretion (GSIS) in islets in stiff scaffolds. Overall, our results emphasize the role mechanical properties of the islet microenvironment plays in regulating function. It also supports further investigation into the modulation of Piezo1 channel activity to restore islet function in diseases like type 2 diabetes (T2D) and pancreatic cancer where fibrosis of the peri-islet ECM leads to increased tissue stiffness and islet dysfunction.

Remnant Preservation of the Primary Vertical Graft in Revision Anterior Cruciate Ligament Reconstruction.

Background: The remnant preservation of a primary vertical graft in revision anterior cruciate ligament reconstruction (ACLR) can benefit anteroposterior stability. However, studies that address this concept are rare. Purpose: To evaluate clinical outcomes of remnant preservation of primary vertical graft in revision ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 74 patients with revision ACLR were included in this retrospective study. Remnant preservation revision ACLR was performed only in patients with primary vertical grafts. The patients were divided into 2 groups according to whether the primary remnant vertical graft was preserved (remnant group; n = 48) or absent or sacrificed (no-remnant group; n = 26). The remnant group was further divided according to the degree of remnant tissue: sufficiently preserved subgroup (graft coverage, ≥50%; n = 25) and insufficiently preserved subgroup (graft coverage, <50%; n = 23). Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) subjective form, Lysholm score, Tegner activity scale, manual laxity tests, and side-to-side difference in anterior tibial translation on Telos stress radiographs. Results: The mean time to final follow-up was 40.7 ± 16.8 months. The remnant group showed more improved results in the postoperative Lachman test and Telos side-to-side difference than did the no-remnant group (P = .017 and .016, respectively). The post hoc test revealed that the side-to-side difference in laxity in the sufficiently preserved subgroup significantly outperformed that in the no-remnant group (P = .001), although no significant difference existed between the insufficiently preserved and no-remnant subgroups (P = .850). The postoperative IKDC subjective form, Lysholm score, and Tegner activity scale did not show significant differences between the 2 groups (P = .480, .277, and .883, respectively). Conclusion: The remnant preservation of the primary vertical graft in revision ACLR may result in better anteroposterior stability. However, subjective outcomes in the remnant group did not exceed that of the no-remnant group. The subgroup analysis revealed that only sufficiently preserved remnants demonstrated better anteroposterior stability.

Radiological evaluation of atlantoaxial fusion using C2 translaminar screws and C2 pedicle screws: Does the screw halo sign imply fusion failure?

The purpose of this study was to identify the criteria for atlantoaxial (AA) fusion by comparing follow-up lateral radiographs and computed tomography (CT) images. We retrospectively analyzed data from 161 consecutive patients undergoing AA fusion. Patients with a minimum of 1 year of CT follow-up after AA fusion surgery using C2 pedicle screws or translaminar screws (C2TLS) were included. Patients were followed up radiographically at 3, 6, and 12 months after surgery, and dynamic lateral radiographs were also evaluated. A total of 49 patients were analyzed, with a mean CT image follow-up of 41.6 ±â€…37.6 months. Thirty eight patients had C2 pedicle screw placement, and 11 patients underwent planned C2TLS. AA fusion with bridging bone mass formation was achieved in 45/49 (91.8%) patients. Screw halos were observed in 14/49 (28.6%) patients. Among them, final fusion failure occurred in 2 (14.3%) patients. The last follow-up CT showed no difference in the fusion failure rate according to the presence or absence of a screw halo (no halo, 5.7%; halo, 14.3%; P = .33). The differences in C1-2 segmental angles (SA) in flexion-extension dynamic lateral radiographs were 1.99 ±â€…1.62° in the fusion group and 4.37 ±â€…2.13° in the non-fusion group (P = .01). The likelihood of fusion failure increased when the SA gap was greater than 2.62° (P = .05). C2TLS placement had a significantly higher incidence of screw halos. However, the halo sign was not significantly related to final bone fusion. Bone fusion could be predicted when the SA gap of C1-2 was less than 2.62° on the dynamic radiograph.

Making a Painless Drain: Proof of Concept.

Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations.

Indirect Decompression Using Oblique Lumbar Interbody Fusion Revision Surgery Following Previous Posterior Decompression: Comparison of Clinical and Radiologic Outcomes Between Direct and Indirect Decompression Revision Surgery.

OBJECTIVE: This study compared the radiological and clinical outcomes with transforaminal lumbar interbody fusion (TLIF) to evaluate the effect of indirect decompression through oblique lumbar interbody fusion (OLIF) as revision surgery. METHODS: We enrolled patients who underwent single-level fusion with revision surgery at the same level as the previous decompression level. We retrospectively reviewed 25 patients who underwent OLIF from 2017 to 2018 and 25 who received TLIF from 2014 to 2018. Radiologic and clinical outcomes were evaluated by cross-sectional area (CSA) of the spinal canal, thickness and area of ligamentum flavum (LF), subsidence, disc height, fusion rate, Oswestry Disability Index (ODI), and visual analogue scale (VAS). RESULTS: Compared with OLIF, the thickness and area of the LF after surgery were significantly less in TLIF, and the resulting CSA extension was also significantly higher. However, both groups showed improvement in ODI and VAS after surgery, and there was no difference between the groups. Complications related to the posterior approach in TLIF were 4 cases, and in OLIF, there were 2 cases that underwent additional posterior decompression surgery and 6 cases of transient paresthesia. CONCLUSION: Since complications associated with the posterior approach can be avoided, OLIF is a safer and useful minimally invasive surgery. Therefore, appropriate indications are applied, OLIF is a good alternative to TLIF when revision surgery is considered.

Sulfonated Thermoresponsive Injectable Gel for Sequential Release of Therapeutic Proteins to Protect Cardiac Function after Myocardial Infarction.

Myocardial infarction causes cardiomyocyte death and persistent inflammatory responses, which generate adverse pathological remodeling. Delivering therapeutic proteins from injectable materials in a controlled-release manner may present an effective biomedical approach for treating this disease. A thermoresponsive injectable gel composed of chitosan, conjugated with poly(N-isopropylacrylamide) and sulfonate groups, was developed for spatiotemporal protein delivery to protect cardiac function after myocardial infarction. The thermoresponsive gel delivered vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and platelet-derived growth factor (PDGF) in a sequential and sustained manner in vitro. An acute myocardial infarction mouse model was used to evaluate polymer biocompatibility and to determine therapeutic effects from the delivery system on cardiac function. Immunohistochemistry showed biocompatibility of the hydrogel, while the controlled delivery of the proteins reduced macrophage infiltration and increased vascularization. Echocardiography showed an improvement in ejection fraction and fractional shortening after injecting the thermal gel and proteins. A factorial design of experimental study was implemented to optimize the delivery system for the best combination and doses of proteins for further increasing stable vascularization and reducing inflammation using a subcutaneous injection mouse model. The results showed that VEGF, IL-10, and FGF-2 demonstrated significant contributions toward promoting long-term vascularization, while PDGF's effect was minimal.

Cervical Radiculopathy Caused by Spinal Epidural Arteriovenous Fistula (SEDAVF) Without Intradural Drainage: A Case Report and Literature Review.

Spinal epidural arteriovenous fistula (SEDAVF) is a rare vascular malformation. Due to the mass effect of enlarged epidural veins and venous hypertension, progressive radiculopathy and myelopathy are likely to occur. A 33-year-old female presented with right upper extremity weakness for a month. The cause of this symptom was a SEDAVF, which was located near the C5-6-7 foramens and compressed the nerve roots. In the absence of intradural venous drainage, endovascular treatment is often difficult because of the large venous pouch. We performed endovascular trapping of the vertebral artery (VA) and loose packing of the coil material on the AVF to minimize mass effects. Immediately after embolization, the fistula was occluded, but a small new feeder vessel developed a day later. An n-butyl cyanoacrylate embolization was performed, and the fistula was successfully occluded.

Preliminary Results of a Reverse Thermal Gel Patch for Fetal Ovine Myelomeningocele Repair.

BACKGROUND: Prenatal surgical closure of Myelomeningocele (MMC) is considered part of the current age armamentarium. Clinical data has demonstrated the need for innovative patches to maximize the benefits and decrease the risks of this approach. Our team has developed a minimally invasive reverse thermal gel (RTG) patch with cellular scaffolding properties. Here, we demonstrate the initial gross and microscopic histological effects of this RTG patch in the fetal ovine model of MMC. MATERIALS AND METHODS: A fetal ovine MMC defect was created at 68-75 days gestation, RTG patch application or untreated at 100-103 days, and harvest at 135-140 days. The RTG was applied to the defect and secured in place with an overlay sealant. Defect areas underwent gross and microscopic analysis for inflammation and skin development. Brains were analyzed for hindbrain herniation and hydrocephalus. RESULTS: The untreated fetus (n = 1) demonstrated an open defect lacking tissue coverage, evidence of spinal cord injury, increased caspase-3, Iba1 and GFAP in spinal cord tissues, and hindbrain herniation and ventricular dilation. RTG treated fetuses (n = 3) demonstrated defect healing with well-organized dermal and epidermal layers throughout the entire healed tissue area overlaying the defect with minimal inflammation, reduced caspase-3, Iba1 and GFAP in spinal cord tissues, and no hindbrain herniation or ventricular dilation. CONCLUSION: An RTG patch applied to MMC defects in fetal sheep promoted skin coverage over the defect, was associated with minimal inflammation of the spinal cord tissues and prevented brain abnormalities. The present findings provide exciting results for future comprehensive radiological, functional, and mechanistic evaluation of the RTG.

Enhanced osteogenic differentiation of alendronate-conjugated nanodiamonds for potential osteoporosis treatment.

BACKGROUND: Alendronate (Alen) is promising material used for bone-targeted drug delivery due to its high bone affinity and therapeutic effects on bone diseases. In addition, Alen can enhance the osteogenic differentiation of osteoblastic cell. Recently, nanodiamonds (NDs) with hardness, non-toxicity, and excellent biocompatibility are employed as promising materials for carrier systems and osteogenic differentiation. Therefore, we prepared Alen-conjugated NDs (Alen-NDs) and evaluated their osteogenic differentiation performances. METHODS: Alen-NDs were synthesized using DMTMM as a coupling reagent. Morphological change of Mouse calvaria-derived preosteoblast (MC3T3-E1) treated with Alen-NDs was observed using the confocal microscope. The osteogenic differentiation was confirmed by cell proliferation, alkaline phosphatase (ALP), calcium deposition, and real-time polymerase chain reaction assay. RESULTS: Alen-NDs were prepared to evaluate their effect on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. The Alen-NDs had a size of about 100 nm, and no cytotoxicity at less than 100 µg/mL of concentration. The treatment of NDs and Alen-NDs reduced the proliferation rate of MC3T3-E1 cells without cell death. Confocal microscopy images confirmed that the treatment of NDs and Alen-NDs changed the cellular morphology from a fibroblastic shape to a cuboidal shape. Flow cytometry, alkaline phosphatase (ALP) activity, calcium deposition, and real-time polymerase chain reaction (RT-PCR) confirmed the higher differentiation of MC3T3-E1 cells treated by Alen-NDs, compared to the groups treated by osteogenic medium and NDs. The higher concentration of Alen-ND treated in MC3T3-E1 resulted in a higher differentiation level. CONCLUSIONS: Alen-NDs can be used as potential therapeutic agents for osteoporosis treatment by inducing osteogenic differentiation.

Immunomagnetic microfluidic integrated system for potency-based multiple separation of heterogeneous stem cells with high throughput capabilities.

Multipotent adult stem cells (MASCs) derived from Pluripotent stem cells (PSCs) have found widespread use in various applications, including regenerative therapy and drug screening. For these applications, highly pluripotent PSCs need to be selectively separated from those that show low pluripotency for reusage of PSCs, and MASCs need to be collected for further application. Herein, we developed immunomagnetic microfluidic integrated system (IM-MIS) for separation of stem cells depending on potency level. In this system, each stem cell was multiple-separated in microfluidics chip by magnetophoretic mobility of magnetic-activated cells based on the combination of two sizes of magnetic nanoparticles and two different antibodies. Magnetic particles had a difference in the degree of magnetization, and antibodies recognized potency-related surface markers. IM-MIS showed superior cell separation performance than FACS with high throughput (49.5%) in a short time (<15 min) isolate 1 × 107 cells, and higher purity (92.1%) than MACS. IM-MIS had a cell viability of 89.1%, suggesting that IM-MIS had no effect on cell viability during isolation. Furthermore, IM-MIS did not affect the key characteristics of stem cells including its differentiation potency, phenotype, genotype, and karyotype. IM-MIS may offer a new platform for the development of multi-separation systems for diverse stem cell applications.

AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections.

Metabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2-/- murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

Preventive Effects against Retinal Degeneration by Centella asiatica Extract (CA-HE50) and Asiaticoside through Apoptosis Suppression by the Nrf2/HO-1 Signaling Pathway.

Age-related macular degeneration (AMD) is caused by the chronic and gradual oxidative degeneration of the retina. Unfortunately, the general purpose of current treatments is to slow AMD progression, as the retina cannot be restored to its pre-AMD condition. We aimed to identify natural products that can be potential treatments that prevent AMD and can delay the development of late-AMD and selected Centella asiatica extract (CA-HE50), which shows excellent efficacy in cytoprotection. In animal experiments using N-methyl-N-nitrosourea (MNU), CA-HE50 dramatically increased the thickness of photoreceptors and the outer nuclear layer (ONL) and the number of nuclei in the ONL (p < 0.05). Using retinal epithelial ARPE-19 cells showed that CA-HE50 inhibited apoptosis through inhibition of the intrinsic apoptosis signaling pathway and cell cycle regulation (p < 0.05). The anti-apoptotic efficacy was confirmed to be due to activation of the Nrf2/HO-1 antioxidation pathway (p < 0.05). These results were also observed with asiaticoside, a functional substance of CA-HE50. In addition, the accumulation of oxidized-N-retinylidene-N-retinylethanolamine (A2E), which induces AMD, was inhibited by CA-HE50, resulting in increased ARPE-19 cell viability (p < 0.05). This study demonstrates that CA-HE50 is worth further research and human application tests, to develop it as a raw material for treatment or dietary supplement for the prevention of AMD.

In vivo monitoring platform of transplanted human stem cells using magnetic resonance imaging.

As stem cells show great promise in regenerative therapy, stem cell-mediated therapeutic efficacy must be demonstrated through the migration and transplantation of stem cells into target disease areas at the pre-clinical level. In this study, we developed manganese-based magnetic nanoparticles with hollow structures (MnOHo) and modified them with the anti-human integrin ß1 antibody (MnOHo-Ab) to enable the minimal-invasive monitoring of transplanted human stem cells at the pre-clinical level. Compared to common magnetic resonance imaging (MRI)-based stem cell monitoring systems that use pre-labeled stem cells with magnetic particles before stem cell injection, the MnOHo-Ab is a new technology that does not require stem cell modification to monitor the therapeutic capability of stem cells. Additionally, MnOHo-Ab provides improved T1 MRI owing to the hollow structure of the MnOHo. Particularly, the anti-integrin ß1 antibody (Ab) introduced in the MnOHo targets integrin ß1 expressed in the entire stem cell lineage, enabling targeted monitoring regardless of the differentiation stage of the stem cells. Furthermore, we verified that intravenously injected MnOHo-Ab specifically targeted human induced pluripotent stem cells (hiPSCs) that were transferred to mice testes and differentiated into various lineages. The new stem cell monitoring method using MnOHo-Ab demonstrates whether the injected human stem cells have migrated and transplanted themselves in the target area during long-term stem cell regenerative therapy.

One-Stage Anatomical Revision Anterior Cruciate Ligament Reconstruction: Results According to Tunnel Overlaps.

PURPOSE: To present clinical results according to tunnel overlap in 1-stage anatomical revision anterior cruciate ligament reconstruction (ACLR). METHODS: All patients who underwent revision ACLR performed by a single surgeon (J.H.A.) from 2012 to 2017 and were followed up for >24 months were retrospectively evaluated. The exclusion criteria were concomitant ligament injury, including medial collateral ligament injury, modified Outerbridge grade ≥3 cartilage lesion, and severe meniscus defects. Tunnel overlap was measured on 3-dimensionally reconstructed computed tomography images. Patients in the nonoverlapped femoral tunnel group (group NO, n = 52) were treated with new tunnel drilling that completely avoided previous tunnels, and those in the overlapped femoral tunnel group (group O, n = 41) were treated with a new tunnel that overlapped with previous tunnels. Clinical outcomes were evaluated using the subjective International Knee Documentation Committee (IKDC) and Lysholm scores. Knee joint stability was measured using the Lachman and pivot shift tests. Patients with femoral tunnel widening of ≥14 mm underwent 2-stage ACLR. RESULTS: The mean follow-up duration of 93 patients was 46.9 months (range, 24-97 months). All preoperative subjective and objective IKDC (P<0.001) and Telos stress test scores (P = .016) were significantly improved at the last follow-up. Forty-one patients had overlapping femoral tunnels, whereas 87 had overlapping tibial tunnels. At the last follow-up, subjective IKDC and Lysholm scores (73.6 ± 15.3 vs 74.9 ± 12.1, P = .799 and 80.0 ± 19.2 vs 81.44 ± 13.5, P = .505, respectively) and objective pivot shift (IKDC grade) in the Lachman test (P = .183 and P = .450, respectively) did not differ significantly between groups NO and O, respectively. CONCLUSIONS: One-stage anatomical revision ACLR significantly improved the clinical results. Most tibial tunnels (94%) and approximately one-half (44%) of the femoral tunnels overlapped. The overlapped femoral tunnel group did not show inferior outcomes or stability. LEVEL OF EVIDENCE: Level III, cohort study.

Co-delivery of antigens and immunostimulants via a polymersome for improvement of antigen-specific immune response.

Cellular uptake of antigens (Ags) by antigen-presenting cells (APCs) is vital for effective functioning of the immune system. Intramuscular or subcutaneous administration of vaccine Ags alone is not sufficient to elicit optimal immune responses. Thus, adjuvants are required to induce strong immunogenicity. Here, we developed nanoparticulate adjuvants that assemble into a bilayer spherical polymersome (PSome) to promote the cellular uptake of Ags by APCs. PSomes were synthesized by using a biodegradable and biocompatible block copolymer methoxy-poly(ethylene glycol)-b-poly(d,l-lactide) to encapsulate both hydrophilic and lipophilic biomacromolecules, such as ovalbumin (OVA) as a model Ag and monophosphoryl lipid A (MPLA) as an immunostimulant. After co-encapsulation of OVA and MPLA, the PSome synthetic vehicle exhibited the sustained release of OVA in cell environments and allowed efficient delivery of cargos into APCs. The administration of PSomes loaded with OVA and MPLA induced the production of interleukin-6 and tumor necrosis factor-alpha cytokines by macrophage activation in vitro and elicited effective Ag-specific antibody responses in vivo. These findings indicate that the nano-sized PSome may serve as a potent adjuvant for vaccine delivery systems to modulate enhanced immune responses.

Three-Dimensional Morphometric Analysis of Penetrative Depth and Size of Nonarthritic and Degenerative Arthritic Glenoids: Implications for Glenoid Replacement in Shoulder Arthroplasty.

BACKGROUND: Shoulder arthroplasty is technically demanding and relies heavily on the precision of surgical techniques. Proper glenoid component sizing plays a crucial role in successful shoulder arthroplasty. We measured the size and penetrative depth of the glenoid for peg or screw fixation in nonarthritic and degenerative arthritic shoulders by using three-dimensional computed tomography to determine the reference dimensions of the glenoid in nonarthritic and degenerative arthritic shoulders. METHODS: From January 2010 to January 2011, data on two groups of patients were collected and reviewed. Group 1 comprised 38 patients who underwent surgical treatment due to fracture of the proximal humerus and who had no evidence of a pathological glenoid. Group 2 comprised 14 patients who underwent surgical treatment due to osteoarthritis of the glenohumeral joint. The height (maximal superoinferior diameter) of the glenoid was measured, and the width (anteroposterior [AP] diameter) of the glenoid was measured at five different levels (H1-H5). Axial images were taken at H1-H5 levels, the AP glenoid diameter of each was divided into eight areas, and division points were labeled as W1-W7. The penetrative depths between the near cortex and far cortex of the glenoid (thickness) at each point (W1-W7) were measured. RESULTS: The overall mean glenoid height was 37.67 ± 4.09 mm in nonarthritic glenoids and 39.42 ± 3.54 mm in degenerative arthritic glenoids. The nonarthritic glenoid was significantly thicker than the degenerative arthritic glenoid at the H1W3, H1W4, H1W5, H2W7, H3W1, H3W6, H3W7, H4W5, H4W6, H4W7, H5W4, H5W5, H5W6, and H5W7 points. The posteroinferior quadrant had the smallest penetrative depth in both nonarthritic and degenerative arthritic glenoids. Also, the degenerative arthritic glenoids were significantly thinner than the nonarthritic glenoids along the posterior and inferior parts of the glenoid. CONCLUSIONS: The posterior and inferior parts of the degenerative arthritic glenoid appears thinner than the nonarthritic glenoid. Thus, caution has to be taken when drilling the screw hole or inserting screws into the posteroinferior parts, where the glenoid is thinner than 15 mm on average, to avoid penetration of the far cortex.

Improved Coverage of Mouse Myelomeningocele With a Mussel Inspired Reverse Thermal Gel.

BACKGROUND: Myelomeningocele (MMC) is an open neural tube defect of the spinal column. Our laboratory previously introduced a reverse thermal gel (RTG) as the first in situ forming patch for in utero MMC application. To overcome the challenges of anchoring the RTG in the wet amniotic environment to improve MMC coverage, we modified the RTG to mimic the underwater adhesive properties of mussels. We have separated this study into three separate hypotheses-based components: CONCLUSIONS: The DRTG demonstrates increased elasticity, cellular scaffolding properties, and improved MMC coverage in the Grhl3 mouse model. Future studies will be translated to the preclinical ovine model to evaluate this novel gel.

Online Tuning of PID Controller Using a Multilayer Fuzzy Neural Network Design for Quadcopter Attitude Tracking Control.

This study presents an online tuning proportional-integral-derivative (PID) controller using a multilayer fuzzy neural network design for quadcopter attitude control. PID controllers are simple but effective control methods. However, finding the suitable gain of a model-based controller is relatively complicated and time-consuming because it depends on external disturbances and the dynamic modeling of plants. Therefore, the development of a method for online tuning of quadcopter PID parameters may save time and effort, and better control performance can be achieved. In our controller design, a multilayer structure was provided to improve the learning ability and flexibility of a fuzzy neural network. Adaptation laws to update network parameters online were derived using the gradient descent method. Also, a Lyapunov analysis was provided to guarantee system stability. Finally, simulations concerning quadcopter attitude control were performed using a Gazebo robotics simulator in addition to a robot operating system (ROS), and their results were demonstrated.

Injectable Polymeric Delivery System for Spatiotemporal and Sequential Release of Therapeutic Proteins To Promote Therapeutic Angiogenesis and Reduce Inflammation.

Myocardial infarction (MI) causes cardiac cell death, induces persistent inflammatory responses, and generates harmful pathological remodeling, which leads to heart failure. Biomedical approaches to restore blood supply to ischemic myocardium, via controlled delivery of angiogenic and immunoregulatory proteins, may present an efficient treatment option for coronary artery disease (CAD). Vascular endothelial growth factor (VEGF) is necessary to initiate neovessel formation, while platelet-derived growth factor (PDGF) is needed later to recruit pericytes, which stabilizes new vessels. Anti-inflammatory cytokines like interleukin-10 (IL-10) can help optimize cardiac repair and limit the damaging effects of inflammation following MI. To meet these angiogenic and anti-inflammatory needs, an injectable polymeric delivery system composed of encapsulating micelle nanoparticles embedded in a sulfonated reverse thermal gel was developed. The sulfonate groups on the thermal gel electrostatically bind to VEGF and IL-10, and their specific binding affinities control their release rates, while PDGF-loaded micelles are embedded in the gel to provide the sequential release of the growth factors. An in vitro release study was performed, which demonstrated the sequential release capabilities of the delivery system. The ability of the delivery system to induce new blood vessel formation was analyzed in vivo using a subcutaneous injection mouse model. Histological assessment was used to quantify blood vessel formation and an inflammatory response, which showed that the polymeric delivery system significantly increased functional and mature vessel formation while reducing inflammation. Overall, the results demonstrate the effective delivery of therapeutic proteins to promote angiogenesis and limit inflammatory responses.

CAU-11-COOH with a V-Shaped Linker as a Catalyst for the Solvent-Free Synthesis of Cyclic Carbonates from CO2 and Epoxides.

An Al3+-based metal-organic framework (MOF), CAU-11-COOH, with a V-shaped ligand, DPSDA (3,3'-4,4'-diphenylsulfonetetracarboxylic dianhydride), was prepared using the solvothermal method, and was characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, elemental analysis, thermogravimetric analysis, Brunauer-Emmett-Teller analysis, and CO2 adsorption. The catalytic efficiency of CAU-11-COOH was investigated in the solvent-free cycloaddition of carbon dioxide with epoxides, which yielded five-membered cyclic carbonates under mild reaction conditions. CAU-11-COOH with a co-catalyst, tetrabutylammonium bromide (TBAB), gave higher than 98% yield of epichlorohydrin carbonate at 80 °C without a solvent. A plausible reaction mechanism in which the Lewis acidic metal center, an uncoordinated carboxyl group, and a nucleophilic bromide anion operate synergistically is proposed. The CAU-11-COOH catalysts were found to exhibit high thermal stability and could be reused more than four times without any significant reduction in activity.