Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p.

BACKGROUND: Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. METHODS: The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. RESULTS: F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and ß-catenin. CONCLUSION: F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.

Controlled posterior condylar milling technique for unicompartmental knee arthroplasty minimises tibia resection during gap balancing: Short-term clinical results.

PURPOSE: The purpose of this study was to demonstrate the clinical utility of controlled posterior condylar milling (CPCM) in gap balancing while minimally resecting the tibia during fixed-bearing unicompartmental knee arthroplasty (UKA). METHODS: This study is a retrospective cohort study. Patients who underwent medial UKA for isolated medial compartment osteoarthritis with a minimum follow-up of 2 years were included. The patients were divided into two groups: the conventional group (n = 56) and the CPCM group (n = 66). In the CPCM group, the proximal tibia was resected at the level of the distal end of the subchondral bone. If the flexion gap was tighter than extension, the posterior condyle was additionally milled to adjust gap tightness. Standing knee X-ray and scanogram were used to evaluate alignment and tibia resection amount. Range of motion (ROM) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate clinical outcomes. RESULTS: The CPCM group showed significantly smaller tibia resection (3.6 ± 1.9 mm) compared to the conventional group (5.2 ± 2.7 mm) (p < 0.001). Postoperative ROM (133.0 ± 8.3°, 135.2 ± 7.2°, n.s.) and WOMAC (19.3 ± 13.6, 23.6 ± 17.7, n.s.) were not significantly different between the two groups. Postoperative periprosthetic fractures occurred in two patients in conventional group, while the CPCM group had no periprosthetic fractures. CONCLUSION: The CPCM technique may be a simple and useful intraoperative technique that can achieve minimal tibia resection and promising clinical outcomes while easily adjusting gap tightness between flexion and extension during medial fixed-bearing UKA. LEVEL OF EVIDENCE: Level III.

Suprapatellar intramedullary nail combined with screw fixation has comparable surgical outcomes to minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures.

PURPOSE: To compare union rate, union time, alignment, and complication rate in ipsilateral tibia plateau and shaft fractures treated via suprapatellar intramedullary nailing with screw fixation and minimally invasive locking plate fixation. MATERIALS AND METHODS: A retrospective study was conducted on 48 patients who underwent minimally invasive plate fixation (n = 35) or suprapatellar intramedullary nailing with screw fixation (n = 13), for the treatment of ipsilateral tibial plateau and shaft fractures with at least 1-year follow-up. Union rate, union time, radiologic alignment, and complication rate such as malalignment, nonunion, and fracture-related infection (FRI) were investigated. RESULTS: Demographic data were not different between the two groups. Coronal plane alignment was 0.17 ± 4.23 in the plate group and -0.48 ± 4.17 in the intramedullary nail group (p = 0.637). Sagittal plane alignment was -0.13 ± 5.20 in the plate group and -1.50 ± 4.01 in the suprapatellar intramedullary nail group (p = 0.313). Coronal and sagittal malalignment recorded equal results: (p > 0.99), FRI (p = 0.602), nonunion and union times recorded (p = 0.656) and (p = 0.683, 0.829), respectively, and showed no significant difference between the two groups. CONCLUSION: Suprapatellar intramedullary nailing with screw fixation had similar surgical outcomes with minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures in terms of union rate, union time, alignment, and complication rate. Thus, frequent use of intramedullary nailing combined with screw fixation is anticipated in patients with ipsilateral tibial plateau and shaft fractures when the soft tissue condition is not desirable. LEVEL OF EVIDENCE: Level III.

Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS: Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including  TGF-ß-only, CTGF-only, and TGF-ß + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS: Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-ß and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION: Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

Fixed-Bearing Unicompartmental Knee Arthroplasty in Tibia Vara Knees Results in Joint Surface Malalignment and Varus Joint Line Obliquity, but Does Not Affect Functional Outcomes at Greater Than 5 Years Follow-Up.

BACKGROUND: This study aimed to investigate the clinical outcomes of fixed-bearing medial unicompartmental knee arthroplasty (UKA) for tibia vara knees and the associated changes in joint space malalignment (JSM) and joint line obliquity (JLO). METHODS: We retrospectively analyzed a consecutive group of 100 patients who underwent fixed-bearing medial UKA with a preoperative medial proximal tibia angle (MPTA) ≥86° (n = 50) and MPTA <86° (n = 50) and who had a minimum 5-year follow-up. Radiological parameters, including the hip-knee-ankle angle, MPTA, and the postoperative JSM and JLO, were measured. Functional evaluation was performed using the range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The MPTA <86° group showed significantly higher postoperative JLO (91.8 versus 90.4°, respectively; P = .002) and JSM (6.1 versus 4.2°, respectively; P = .026) compared to the MPTA ≥86° group. Functional outcomes, including range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores, were not significantly different between the 2 groups. CONCLUSIONS: Fixed-bearing medial UKA is a safe and effective surgical option for patients who have tibia vara knees, as an increase in JLO and JSM postoperatively does not have a clinically relevant impact, even after a minimum 5-year follow-up.

Can bone scintigraphy reflect the progression of osteoarthritis after unicompartmental knee arthroplasty?

BACKGROUND: Bone scintigraphy (BS) has been reported to be a useful predictor of osteoarthritis (OA) progression in primary knee OA. However, no previous studies have explored the relationship between BS and OA progression in the retained compartments after unicompartmental knee arthroplasty (UKA). Thus, we evaluated whether OA progresses to other compartments in patients who undergo UKA and if increased uptake on BS is associated with OA progression in other compartments after UKA. METHODS: A total of 41 patients with knee BS at least five years after UKA were included. Radiographic OA progression in other compartments was assessed by grading and comparing OA severity in each patient using the Kellgren-Lawrence grading system (K-L grade) and Osteoarthritis Research Society International (OARSI) atlas score. After UKA, the correlation between BS uptake and radiographic OA progression was analyzed in each retained compartment. A correlation analysis was also performed to evaluate the association between BS uptake and OA progression grades. RESULTS: A significant progression of OA was observed in both contralateral tibiofemoral and patellofemoral compartments after UKA at 98.5 ± 26.0 months of follow-up (all p<0.001). No correlation was found between BS uptake and radiographic OA progression nor between BS uptake and radiographic OA progression grade in the contralateral and patellofemoral compartments. CONCLUSIONS: Following UKA, OA progresses in the retained contralateral tibiofemoral and patellofemoral compartments over a minimum five-year follow-up period. Thus, BS is ineffective in assessing the progression of OA in these compartments.

Rotational stability can be enhanced in revision anterior cruciate ligament reconstruction using the over-the-top augmentation technique compared to single bundle technique.

PURPOSE: Revision anterior cruciate ligament (ACL) reconstruction is technically challenging due to mispositioned tunnels, bone loss, and tunnel enlargement, which may compromise graft fixation and result in failure. To obtain firm graft fixation and strength in one stage, we utilized an over-the-top augmentation technique using an Achilles tendon allograft in revision ACL reconstruction (OA-ACLR). This study compared OA-ACLR with single-bundle ACL reconstruction (SB-ACLR). We hypothesized that OA-ACLR would enhance the postoperative knee joint rotational stability. METHODS: We retrospectively analyzed 47 patients who underwent revisional OA-ACLR and 48 who underwent primary SB-ACLR with minimum follow-up of 6 months. Knee instability was evaluated with the anterior drawer, Lachman, and pivot shift tests preoperatively and at the final follow-up. Side-to-side differences were compared with the non-affected side at the final follow-up. Function was evaluated using the IKDC subjective and Lysholm knee scores preoperatively and at the final follow-up. RESULTS: The groups did not differ in terms of sex, age, BMI, and etiology. There were no significant differences in concomitant surgical procedures, such as meniscectomy and meniscus repair, between the two groups (p = 0.335, > 0.99). Both groups significantly improved in the anterior drawer, Lachman, pivot shift tests, and IKDC and Lysholm knee scores after surgery (all p < 0.001). The OA-ACLR group showed significantly higher rotational stability in the pivot shift test than the SB-ACLR group (p = 0.017). The postoperative side-to-side difference, the IKDC and Lysholm scores showed no significant differences between the groups (p = 0.34, 0.301, 0.438). CONCLUSIONS: OA-ACLR showed enhanced rotational stability with pivot shift test compared to SB-ACLR. It may be considered a useful alternative for revision ACL reconstruction.

Selective Extracellular Matrix Guided Mesenchymal Stem Cell Self-Aggregate Engineering for Replication of Meniscal Zonal Tissue Gradient in a Porcine Meniscectomy Model.

Degenerative meniscus tears (DMTs) are prevalent findings in osteoarthritic knees, yet current treatment is mostly limited to arthroscopic partial meniscectomy rather than regeneration, which further exacerbates arthritic changes. Translational research regarding meniscus regeneration is hindered by the complex, composite nature of the meniscus which exhibit a gradient from inner cartilage-like tissue to outer fibrous tissue, as well as engineering hurdles often requiring growth factors and cross-linking agents. Here, a meniscus zonal tissue gradient is proposed using zone-specific decellularized meniscus extracellular matrix (DMECM) and autologous synovial mesenchymal stem cells (SMSC) via self-aggregation without the use of growth factors or cross-linking agents. Combination with zone-specific DMECM during self-aggregation of MSCs forms zone-specific meniscus tissue that reflects the respective DMECM harvest site. The implantation of these constructs leads to the regeneration of meniscus tissue resembling the native meniscus, demonstrating inner cartilaginous and outer fibrous characteristics as well as recovery of native meniscal microarchitecture in a porcine partial meniscectomy model at 6 months. In all, the findings offer a potential regenerative therapy for DMTs that may improve current partial meniscectomy-based patient care.

Comparison of suprapatellar intramedullary nailing versus minimal invasive locked plating for proximal tibia fractures.

PURPOSE: To compare the radiological alignment, union time, union rate, and complication rate between suprapatellar intramedullary nails and minimally invasive locking plate fixation in the treatment of proximal tibial fractures. MATERIALS AND METHODS: We retrospectively analyzed 103 patients who underwent plate fixation (n = 50) or suprapatellar intramedullary nailing (n = 53) for proximal tibial fractures involving the meta-diaphyseal junction between November 2015 and October 2020 at our institution. The union rate, union time, radiologic alignments, and complications, such as malalignment, nonunion, and deep infection, were investigated. RESULTS: The demographic data did not differ between the plate and suprapatellar intramedullary nail groups. The alignment of the coronal plane was 0.24 ± 3.19 in the plate group and - 0.49 ± 2.22 in the intramedullary nail group (p = 0.196). Sagittal plane alignment was - 0.29 ± 4.97 in the plate group and 0.24 ± 4.12 in the intramedullary nail group (p = 0.571), and coronal malalignment (p = 0.196), sagittal malalignment (p = 0.57), deep infection (p = 0.264), nonunion (p = 0.695), union time (p = 0.329), and final union rate (p = 0.699) were not significantly different between groups. CONCLUSION: Compared with the minimally invasive locking compression plate group, the suprapatellar intramedullary nail group yielded comparable results in terms of radiological alignment and complications. Considering that proximal tibial fractures are associated with high-energy trauma and severe soft tissue damage, we believe that a suprapatellar intramedullary nail may be a good alternative. LEVEL OF EVIDENCE: Level III.

Fibrocartilage extracellular matrix augmented demineralized bone matrix graft repairs tendon-to-bone interface in a rabbit tendon reconstruction model.

Current tendon/ligament reconstructions integrate via scar tissue rather than proper bone-tendon interface regeneration, which affects graft longevity, changes in bone tunnel size, and functional outcomes. The purpose of this study was to develop a functional demineralized bone matrix (DBM) + fibrocartilage extracellular matrix (FCECM) composite scaffold, characterize its physicochemical properties, and evaluate its efficacy in repairing tendon-bone interface in a rabbit tendon reconstruction model. Solubilized FCECM was loaded and crosslinked on to DBM scaffolds via gamma-irradiation to create DBM + FCECM scaffolds. The resulting scaffold showed interconnected pores coated with FCECM and protein cargo similar to FCECM. The addition of FCECM modified the physicochemical properties of the DBM scaffold, including microstructure, biochemical composition, mechanical strength, thermodynamic properties, and degradation period. The DBM + FCECM scaffold was biocompatible for mesenchymal stem cells (MSCs) and resulted in elevation of fibrochondrogenic gene markers compared to DBM scaffolds in vitro. In vivo implantation of DBM + FCECM scaffold resulted in neofibrocartilage formation, better pullout strength, and less bone tunnel widening compared to DBM only group in a rabbit tendon reconstruction model. In conclusion, the FCECM augmented DBM scaffold repairs the tendon-bone interface with osseous-fibrocartilage tissue, which may be utilized to improve current tendon reconstruction surgeries.

Lateral Retinacular Release During Medial Unicompartmental Knee Arthroplasty in the Presence of Patello-Femoral Joint Arthritis Relieves Patello-Femoral Joint Pressure and Improves Associated Symptoms.

BACKGROUND: This study evaluated the effects of concomitant lateral patellar retinacular release (LPRR) during medial unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively analyzed 100 patients who had patello-femoral joint (PFJ) arthritis who underwent medial UKA with (n = 50) and without (n = 50) LPRR who had ≥2 years follow-up. Radiological parameters associated with lateral retinacular tightness, including patellar tilt angle (PTA), lateral patello-femoral angle (LPFA), and congruence angle, were measured. Functional evaluation was performed using the Knee Society Pain Score, Knee Society Function Score (KSFS), Kujala Score, and the Western Ontario McMaster Universities Osteoarthritis Index score. Intraoperative patello-femoral pressure evaluation was performed on 10 knees to evaluate the pressure changes before and after LPRR. Mann-Whitney U-tests were used for statistical analyses. RESULTS: Demographic data did not differ between the LPRR(+) and LPRR(-) groups. A decrease in PTA and an increase in LPFA were observed in the LPRR(+) group compared to those in the LPRR(-) group (PTA; -0.54 versus -1.74, P = .002, LPFA; 0.51 versus 2.01, P = .010). The LPRR(+) group showed significantly better KSFS and Kujala scores than the LPRR(-) group (KSFS: 90 versus 80, P = .017; Kujala score: 86 versus 79, P = .009). Intraoperative patello-femoral pressure analysis showed a 22.6% reduction in the PFJ contact pressure and an 18.7% reduction in PFJ peak pressure after LPRR. (P = .0015, P < .0001, respectively) CONCLUSION: A LPRR during UKA may be a simple and useful adjunct procedure to relieve PFJ symptoms with concomitant PFJOA.

Antimicrobial activity of Limosilactobacillus fermentum strains isolated from the human oral cavity against Streptococcus mutans.

Oral probiotics have been recently gaining much attention owing to their potential to inhibit the progression of dental caries by controlling the cariogenic effects of Streptococcus mutans. We isolated and genotypically identified 77 lactic acid bacteria including 12 Limosilactobacillus fermentum probiotic candidates from the oral cavity of healthy volunteers. Among the 12 L. fermentum isolates, nine isolates effectively inhibited the growth of S. mutans via hydrogen peroxide (H2O2) production. The others neither suppressed the growth of S. mutans nor produced H2O2. Eight out of the nine H2O2-producing L. fermentum isolates exhibited strong adherence to oral epithelial KB cells while inhibiting the adherence of S. mutans to KB cells. The eight H2O2-producing isolates were neither haemolytic based on a blood-agar test, cytotoxic according to lactate dehydrogenase assay, nor resistant to eight antibiotics represented by the European Food Safety Authority guideline, indicating that the isolates have potential to suppress the cariogenesis driven by S. mutans while providing general probiotic benefits.

Effects of glycosaminoglycan content in extracellular matrix of donor cartilage on the functional properties of osteochondral allografts evaluated by micro-CT non-destructive analysis.

Osteochondral allograft (OCA) is an important surgical procedure used to repair extensive articular cartilage damage. It is known that chondrocyte viability is crucial for maintaining the biochemical and biomechanical properties of OCA, which is directly related to the clinical success of the operation and is the only standard for preoperative evaluation of OCA. However, there is a lack of systematic research on the effect of the content of cellular matrix in OCA cartilage tissue on the efficacy of transplantation. Therefore, we evaluated the effect of different GAG contents on the success of OCA transplantation in a rabbit animal model. Each rabbit OCA was treated with chondroitinase to regulate glycosaminoglycan (GAG) content in the tissue. Due to the different action times of chondroitinase, they were divided into 4 experimental groups (including control group, 2h, 4h, and 8h groups). The treated OCAs of each group were used for transplantation. In this study, transplant surgery effects were assessed using micro-computed tomography (µCT) and histological analysis. Our results showed that tissue integration at the graft site was poorer in the 4h and 8h groups compared to the control group at 4 and 12 weeks in vivo, as were the compressive modulus, GAG content, and cell density reduced. In conclusion, we evaluated the biochemical composition of OCAs before and after surgery using µCT analysis and demonstrated that the GAG content of the graft decreased, it also decreased during implantation; this resulted in decreased chondrocyte viability after transplantation and ultimately affected the functional success of OCAs.

3D Bioprinting Strategies for Articular Cartilage Tissue Engineering.

Articular cartilage is the avascular and aneural tissue which is the primary connective tissue covering the surface of articulating bone. Traumatic damage or degenerative diseases can cause articular cartilage injuries that are common in the population. As a result, the demand for new therapeutic options is continually increasing for older people and traumatic young patients. Many attempts have been made to address these clinical needs to treat articular cartilage injuries, including osteoarthritis (OA); however, regenerating highly qualified cartilage tissue remains a significant obstacle. 3D bioprinting technology combined with tissue engineering principles has been developed to create biological tissue constructs that recapitulate the anatomical, structural, and functional properties of native tissues. In addition, this cutting-edge technology can precisely place multiple cell types in a 3D tissue architecture. Thus, 3D bioprinting has rapidly become the most innovative tool for manufacturing clinically applicable bioengineered tissue constructs. This has led to increased interest in 3D bioprinting in articular cartilage tissue engineering applications. Here, we reviewed current advances in bioprinting for articular cartilage tissue engineering.

Implantation and tracing of green fluorescent protein-expressing adipose-derived stem cells in peri-implant capsular fibrosis.

BACKGROUND: Adipose-derived stem cells (ASCs) have been reported to reduce fibrosis in various tissues. In this study, we investigated the inhibitory role of ASCs on capsule formation by analyzing the histologic, cellular, and molecular changes in a mouse model of peri-implant fibrosis. We also investigated the fate and distribution of ASCs in the peri-implant capsule. METHODS: To establish a peri-implant fibrosis model, customized silicone implants were inserted into the dorsal site of C57BL/6 wild-type mice. ASCs were harvested from the fat tissues of transgenic mice that express a green fluorescent protein (GFP-ASCs) and then injected into the peri-implant space of recipient mice. The peri-implant tissues were harvested from postoperative week 2 to 8. We measured the capsule thickness, distribution, and differentiation of GFP-ASCs, as well as the cellular and molecular changes in capsular tissue following ASC treatment. RESULTS: Injected GFP-ASCs were distributed within the peri-implant capsule and proliferated. Administration of ASCs reduced the capsule thickness, decreased the number of myofibroblasts and macrophages in the capsule, and decreased the mRNA level of fibrogenic genes within the peri-implant tissue. Angiogenesis was enhanced due to trans-differentiation of ASCs into vascular endothelial cells, and tissue hypoxia was relieved upon ASC treatment. CONCLUSIONS: We uncovered that implanted ASCs inhibit capsule formation around the implant by characterizing a series of biological alterations upon ASC treatment and the fate of injected ASCs. These findings highlight the value of ASCs for future clinical applications in the prevention of capsular contracture after implant-based reconstruction surgery.

Long-Term Ultrasonographic and Histologic Changes in Acellular Dermal Matrix in Implant-Based Breast Reconstructions.

BACKGROUND: Acellular dermal matrix (ADM) is composed of extracellular matrix (ECM) and is widely used in implant-based breast reconstructions. However, long-term changes in the ADM around implants have not been established. This study aimed to investigate long-term changes in the ADM covering breast implants using serial ultrasound and histologic evaluations. METHODS: The authors evaluated the ultrasound results of 145 patients who underwent implant-based breast reconstructions with ADM coverings. The ultrasound results obtained within 18 months of surgery and those obtained 5 years postoperatively were analyzed to determine the change in ADM thickness. For histologic analysis, the ADM was harvested from 30 patients who underwent secondary breast surgery. Histologic features of the ECM and cellular components within the ADM were compared at specific intervals from ADM implantation and the second operation (early ADM group, <18 months; late ADM group, >5 years postoperatively). RESULTS: The ADM thickness on ultrasound examination was significantly decreased in the late ADM group compared with that in the early ADM group ( P < 0.001). Histologic analyses revealed that the late ADM group had less thickness with lower ECM levels versus the early ADM group. Increased infiltration of host cells, such as vascular endothelial cells, myofibroblasts, and immune cells, occurred in the late ADM group. CONCLUSIONS: Implanted ADMs underwent gradual thinning over time, in addition to ECM reduction and infiltration of host cells. These findings are useful in understanding the natural course of ADMs currently used in implant-based breast reconstructions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Risk of Dementia in Newly Diagnosed Glaucoma: A Nationwide Cohort Study in Korea.

PURPOSE: To investigate the risk of dementia in participants with newly diagnosed glaucoma. DESIGN: A nationwide cohort study using authorized data provided by the Korean National Health Insurance Service (NHIS). PARTICIPANTS: A total of 788 961 participants aged ≥ 45 years in 2006, who did not have dementia or glaucoma between 2002 and 2005, were included. METHODS: Data were collected from a nationwide population-based retrospective cohort study using the Korean NHIS database. From January 2006 to December 2017, participants were tracked for the diagnosis of glaucoma or dementia using claims data. The prospective association between newly diagnosed glaucoma and the risk of dementia was investigated using a multivariable Cox proportional hazard model adjusted for age, sex, behavioral factors, and systemic and ocular comorbidities. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia development according to the parameters, including glaucoma diagnosis. RESULTS: Overall, 7.0% of the participants developed dementia after an average of 7.4 years. Newly diagnosed glaucoma was associated with a higher risk of dementia (HR, 1.89, 95% CI, 1.57-2.27) independent of age, sex, body mass index, income, smoking and drinking status, visual acuity, and other systemic comorbidities, such as diabetes, hypertension, stroke, and depression. Newly diagnosed glaucoma was associated with higher risk of AD but not VD. The risk of dementia in relation to glaucoma was higher in older participants (HR, 3.15 [≥ 65 years] vs. 1.56 [< 65 years], P < 0.0001). CONCLUSIONS: This nationwide cohort study found that individuals with newly diagnosed glaucoma were at a higher risk of developing dementia, particularly AD. This association was greater among older individuals in the studied population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Aqueous microRNA profiling in age-related macular degeneration and polypoidal choroidal vasculopathy by next-generation sequencing.

Although many studies demonstrated the differences of clinical features, natural course, and response to treatment between typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), differential microRNAs (miRNAs) expression in the aqueous humor (AH) between them has not been reported yet. We investigated the roles of miRNAs in the AH of patients with typical AMD and PCV using next-generation sequencing (NGS) and quantitative PCR (qPCR). Target genes and predicted pathways of miRNAs were investigated via pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database. A total of 161 miRNAs from eyes with typical AMD and 185 miRNAs from eyes with PCV were differentially expressed. 33 miRNAs were commonly upregulated, and 77 miRNAs were commonly downregulated in both typical AMD and PCV groups. Among them, hsa-miR-140-5p, hsa-miR-374c-3p, and hsa-miR-200a-5p were differentially expressed and were predicted to regulate proteoglycans in cancer, p53 signaling pathway, Hippo signaling pathway, and adherens junction. The differential expression profiles and target gene regulation networks of AH miRNAs may contribute to the development of different pathological phenotypes in typical AMD and PCV. The results of this study provide novel insights into the pathogenesis, associated prognostic biomarkers, and therapeutic targets in AMD and PCV.

Border tissue morphology is associated with macular ganglion cell thickness in open-angle glaucoma.

Externally oblique border tissue (EOBT) configuration is topographically associated with glaucomatous damage in the optic nerve head. We investigated the relationship between the EOBT characteristics and macular retinal ganglion cell (RGC) thickness in patients with open-angle glaucoma (OAG). A total of 149 eyes with OAG that had an EOBT observed on optical coherence tomography exams were included. After determining the maximum EOBT length and angular location of the maximal EOBT length, we analyzed their correlation with macular ganglion cell inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. The macular GCIPL and pRNFL thickness were compared based on the angular location of the longest EOBT, and their association was assessed using multivariable regression analysis. Maximum EOBT length was significantly correlated with macular GCIPL thickness, but not with pRNFL thickness. Macular GCIPL was thinnest in eyes with EOBT located in a temporal direction to the optic disc. Longer maximum EOBT and temporally elongated EOBT were independently associated with a thinner macular GCIPL in the multivariable regression analysis. These suggest that temporal elongation of the EOBT may increase the stress and strain on the RGCs derived from the macula and make RGCs more susceptible to glaucoma-inducing damage.

Complete Genome Sequence of Hydrogen Peroxide-Producing Limosilactobacillus fermentum DM072 Isolated from the Human Oral Cavity.

The complete genome of hydrogen peroxide (H2O2)-producing Limosilactobacillus fermentum strain DM072, isolated from the oral cavity of healthy volunteers in South Korea, was sequenced by long-read sequencing and was subsequently corroborated by short-read sequencing. The genome comprises one circular chromosome and one plasmid and lacks antimicrobial resistance genes.