The Impact of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair for Small to Large Rotator Cuff Tears: A Randomized Controlled Trial.

BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (ASES and constant score), and clinical scores (VAS). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (ASES score and constant score), and clinical score (VAS) during the 2-year post-surgery period (all p>0.05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years post-surgery, did not significantly vary between the groups (all p>0.05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity post-surgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.

Massively parallel screen uncovers many rare 3' UTR variants regulating mRNA abundance of cancer driver genes.

Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3' UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors. Further, we introduce untranslated tumor mutational burden (uTMB), a metric reflecting the amount of somatic functional MapUTR variants of a tumor and show its potential in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), demonstrating their cancer-driving potential. Our study elucidates the function of tens of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.

CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.

Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice.

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1ß, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1ß was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1-/- mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.

MnCO3-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers.

Background: Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites. Methods: Cellular uptake, cytotoxicity assay, and in vitro photothermal conversion efficiency of MnCO3-mineralized fluorescent polydopamine nanoparticles (MnCO3-FPNPs) were evaluated using 4T1 breast cancer cells. In vivo dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm2) for 10 min, measuring the size of the tumors every 2 days. Results: At physiological pH (7.4), MnCO3-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn2+ from the FPNPs. At pH 7.4, MnCO3-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO3 maintenance; conversely, at acidic pH (5.4), MnCO3-FPNPs efficiently release Mn2+ ions, thereby resulting in T 1-weighted magnetic resonance (MR) contrast enhancement. MnCO3-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days. Conclusions: Our studies exhibited unique "OFF-ON" activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO3-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.

Copper arsenite-complexed Fenton-like nanoparticles as oxidative stress-amplifying anticancer agents.

We report copper(II) arsenite (CuAS)-integrated polymer micelles (CuAS-PMs) as a new class of Fenton-like catalytic nanosystem that can display reactive oxygen species (ROS)-manipulating anticancer therapeutic activity. CuAS-PMs were fabricated through metal-catechol chelation-based formation of the CuAS complex on the core domain of poly (ethylene glycol)-b-poly(3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer micelles. CuAS-PMs maintained structural robustness under serum conditions. The insoluble state of the CuAS complex was effectively retained at physiological pH, whereas, at endosomal pH, the CuAS complex was ionized to release arsenite and cuprous Fenton catalysts (Cu+ ions). Upon endocytosis, CuAS-PMs simultaneously released hydrogen peroxide (H2O2)-generating arsenite and Fenton-like reaction-catalyzing Cu+ ions in cancer cells, which synergistically elevated the level of highly cytotoxic hydroxyl radicals (•OH), thereby preferentially killing cancer cells. Animal experiments demonstrated that CuAS-PMs could effectively suppress the growth of solid tumors without systemic in vivo toxicity. The design rationale of CuAS-PMs may provide a promising strategy to develop diverse oxidative stress-amplifying agents with great potential in cancer-specific therapy.

Rotator cuff retear after repair surgery: comparison between experienced and inexperienced surgeons.

BACKGROUND: We hypothesized in this study that the characteristics of retear cases vary according to surgeon volume and that surgical outcomes differ between primary and revision arthroscopic rotator cuff repair (revisional ARCR). METHODS: Surgeons performing more than 12 rotator cuff repairs (RCRs) per year were defined as high-volume surgeons, and those performing fewer than 12 RCRs were considered low-volume surgeons. Of the 47 patients who underwent revisional ARCR at our clinic enrolled in this study, 21 cases were treated by high-volume surgeons and 26 cases by low-volume surgeons. In all cases, the interval between primary surgery and revisional ARCR, degree of "acromial scuffing," number of anchors, RCR technique, retear pattern, fatty infiltration, retear size, operating time, and clinical outcome were recorded. RESULTS: During primary surgery, significantly more lateral anchors (p=0.004) were used, and the rate of use of the double-row repair technique was significantly higher (p<0.001) in the high- versus low-volume surgeon group. Moreover, the "cut-through pattern" was observed significantly more frequently among the cases treated by high- versus low-volume surgeons (p=0.008). The clinical outcomes after revisional ARCR were not different between the two groups. CONCLUSIONS: Double-row repair during primary surgery and the cut-through pattern during revisional ARCR were more frequent in the high- versus low-volume surgeon groups. However, no differences in retear site or size, fatty infiltration grade, or outcomes were observed between the groups.

Failure Rates After Revision Arthroscopic Stabilization for Recurrent Anterior Shoulder Instability Based on Anterior Capsulolabral Complex Conditions.

BACKGROUND: A labral retear is an important contributing factor to surgical failure after arthroscopic soft tissue stabilization for recurrent anterior shoulder instability. However, surgeons frequently encounter poor tissue conditions in the anterior capsule, such as capsular tears, during revision surgery. PURPOSE: To analyze the clinical outcomes and failure rates of revision arthroscopic stabilization after failed Bankart repair based on the tissue conditions of the anterior capsule and the labrum. Outcomes were compared for revision after failed Bankart repair because of a labral retear versus a healed labrum but with capsular tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 55 patients who underwent revision arthroscopic stabilization after failed Bankart repair were included. Revision surgery was indicated if patients had a history of recurrent instability with positive apprehension test results, regardless of magnetic resonance imaging (MRI) findings of a labral retear. Patients were allocated into 2 groups based on arthroscopic findings at the time of revision surgery: group 1 consisted of patients who had a healed labrum with definite anterior capsular tears, and group 2 comprised patients who had labral retears without capsular tears. Clinical outcomes were assessed using the American Shoulder and Elbow Surgeons score, Rowe score, and surgical failure rate. RESULTS: Overall, 10 patients were included in group 1, and 45 patients were included in group 2. No capsular tears were detected on preoperative MRI or magnetic resonance arthrography scans in either group, whereas all patients in group 2 had evidence of anterior labral retears on imaging scans. After revision surgery, 9 patients (16.4%) showed surgical failure by 25.6 months postoperatively. Patients in group 1 had a significantly higher surgical failure rate than did those in group 2 (4 patients [40.0%] vs 5 patients [11.1%], respectively; P = .04). The incidence of capsular tears was significantly higher in patients with surgical failure versus those without surgical failure (44.4% vs 13.0%, respectively; P = .04). CONCLUSION: A capsular tear of the anterior capsulolabral complex was an important indicator for surgical failure after revision arthroscopic stabilization. If patients demonstrate symptomatic instability after arthroscopic soft tissue stabilization without evidence of labral retears on imaging scans, an anterior capsular tear should be considered as a possible factor for recurrence.

Outcomes of Simultaneous Bilateral vs Unilateral Distal Chevron Metatarsal Osteotomy in Hallux Valgus Patients Aged ≥60 Years.

BACKGROUND: The purpose of this study was to compare radiographic outcomes of simultaneous bilateral and unilateral distal chevron metatarsal osteotomy (DCMO) in hallux valgus patients aged ≥60 years. METHODS: This retrospective study analyzed consecutive outcomes of simultaneous bilateral DCMO and unilateral DCMO performed between June 2010 and August 2018 in 90 feet of 60 patients. Thirty patients underwent simultaneous bilateral DCMO, and 30 underwent unilateral DCMO. Comparative analysis of radiographic and clinical parameters between a simultaneous bilateral DCMO group (SB) and a unilateral DCMO group (U) was performed. RESULTS: Mean age at surgery (65.7±4.8 vs 65.2±5.2 years), mean length of follow-up period (20.0 vs 18.6 months), and preoperative radiographic parameters were similar between the 2 groups (SB vs U). Mean hallux valgus angle (HVA) improved from 34.2 to 5.4 degrees (correction angle SB 28.8 vs U 28.8 degrees). Mean first-to-second intermetatarsal angle improved from 15.8 to 6.8 degrees (correction angle SB 8.9 vs U 8.9 degrees). Hallux varus deformity was observed in 4 feet (SB 3 vs U 1), and mechanical instability with callus formation in 1 foot in the unilateral group. CONCLUSION: DCMOs in patients aged ≥60 years were radiographically effective and safe, even performed in one stage bilaterally. Radiographic parameters were similar in patients who underwent simultaneous bilateral and unilateral DCMO. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

RNA editing in cancer impacts mRNA abundance in immune response pathways.

BACKGROUND: RNA editing generates modifications to the RNA sequences, thereby increasing protein diversity and shaping various layers of gene regulation. Recent studies have revealed global shifts in editing levels across many cancer types, as well as a few specific mechanisms implicating individual sites in tumorigenesis or metastasis. However, most tumor-associated sites, predominantly in noncoding regions, have unknown functional relevance. RESULTS: Here, we carry out integrative analysis of RNA editing profiles between epithelial and mesenchymal tumors, since epithelial-mesenchymal transition is a key paradigm for metastasis. We identify distinct editing patterns between epithelial and mesenchymal tumors in seven cancer types using TCGA data, an observation further supported by single-cell RNA sequencing data and ADAR perturbation experiments in cell culture. Through computational analyses and experimental validations, we show that differential editing sites between epithelial and mesenchymal phenotypes function by regulating mRNA abundance of their respective genes. Our analysis of RNA-binding proteins reveals ILF3 as a potential regulator of this process, supported by experimental validations. Consistent with the known roles of ILF3 in immune response, epithelial-mesenchymal differential editing sites are enriched in genes involved in immune and viral processes. The strongest target of editing-dependent ILF3 regulation is the transcript encoding PKR, a crucial player in immune and viral response. CONCLUSIONS: Our study reports widespread differences in RNA editing between epithelial and mesenchymal tumors and a novel mechanism of editing-dependent regulation of mRNA abundance. It reveals the broad impact of RNA editing in cancer and its relevance to cancer-related immune pathways.

The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes.

This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral inner nuclear layer should be evaluated in early type 2 diabetic retinopathy.

Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations.

Significant clinical symptoms of Cohen syndrome (CS), a rare autosomal recessive disorder, include intellectual disability, facial dysmorphism, postnatal microcephaly, retinal dystrophy, and intermittent neutropenia. CS has been associated with mutations in the VPS13B (vacuolar protein sorting 13 homolog B) gene, which regulates vesicle-mediated protein sorting and transport; however, the cellular mechanism underlying CS pathogenesis in patient-derived neurons remains uncertain. This report states that autophagic vacuoles accumulate in CS fibroblasts and the axonal terminals of CS patient-specific induced pluripotent stem cells (CS iPSC)-derived neurons; additionally, autophagic flux was significantly increased in CS-derived neurons compared to control neurons. VPS13B knockout HeLa cell lines generated using the CRISPR/Cas9 genome editing system showed significant upregulation of autophagic flux, indicating that VSP13B may be associated with autophagy in CS. Transcriptomic analysis focusing on the autophagy pathway revealed that genes associated with autophagosome organization were dysregulated in CS-derived neurons. ATG4C is a mammalian ATG4 paralog and a crucial regulatory component of the autophagosome biogenesis/recycling pathway. ATG4C was significantly upregulated in CS-derived neurons, indicating that autophagy is upregulated in CS neurons. The autophagy pathway in CS neurons may be associated with the pathophysiology exhibited in the neural network of CS patients.

Connective tissue growth factor (CTGF) regulates the fusion of osteoclast precursors by inhibiting Bcl6 in periodontitis.

Connective tissue growth factor (CTGF), an extracellular matrix protein with various biological functions, is known to be upregulated in multiple chronic diseases such as liver fibrosis and congestive heart failure, but the mechanism it undertakes to cause alveolar bone loss in periodontitis remains elusive. The present study therefore investigates the pathways involving CTGF in chronic periodontitis. RNA sequencing revealed a notable increase in the expression of CTGF in chronic periodontitis tissues. Also, TRAP staining, TRAP activity and bone resorption assays showed that osteoclast formation and function is significantly facilitated in CTGF-treated bone marrow-derived macrophages (BMMs). Interestingly, western blotting and immunofluorescence staining results displayed that CTGF had little effect on the osteoclastogenic differentiation mediated by the positive regulators of osteoclastogenesis such as nuclear factor of activated T cells 1 (NFATc1). However, following results showed that both the mRNA and protein expressions of B cell lymphoma 6 (Bcl6), a transcriptional repressor of "osteoclastic" genes, were significantly downregulated by CTGF treatment. Moreover, CTGF upregulated the expressions of v-ATPase V0 subunit d2 (ATP6v0d2) and Dendritic cell-specific transmembrane protein (DC-STAMP) which are osteoclastic genes specifically required for osteoclast cell-cell fusion in pre-osteoclasts. Findings from this study suggest that CTGF promotes the fusion of pre-osteoclasts by downregulating Bcl6 and subsequently increasing the expression of DC-STAMP in periodontitis. Understanding this novel mechanism that leads to increased osteoclastogenesis in periodontitis may be employed for the development of new therapeutic targets for preventing periodontitis-associated alveolar bone resorption.

Valgus stress ultrasound for medial ulnar collateral ligament injuries in athletes: is ultrasound alone enough for diagnosis?

BACKGROUND: We hypothesized that valgus stress ultrasound would be useful for both identifying medial ulnar collateral ligament (MUCL) tears and assessing the severity of the tears. Hence, we performed valgus stress ultrasound of the elbow in athletes with MUCL injuries, confirmed by magnetic resonance imaging (MRI), to determine whether ultrasound can be used as a diagnostic tool. METHODS: Stress ultrasound and MRI data from 146 athletes with medial elbow pain were compared prospectively. MRI findings for MUCL injuries were classified into 3 levels as follows: low-grade partial tear (≤50%), high-grade partial tear (>50%), and complete tear. The degree of joint laxity on stress ultrasound was evaluated by measuring joint gapping after applying a 2.5-kg load to the wrist. Joint gapping was measured at 30° and 90° of elbow flexion for the dominant arm and nondominant arm, and the differences between the dominant and nondominant arms were determined. RESULTS: A higher degree of MUCL injury on MRI was associated with greater joint gapping in the medial elbow on stress ultrasound. At 30° of elbow flexion, the cutoff value for complete MUCL rupture was 0.5 mm (P < .001), with a sensitivity and specificity of 88.1% and 61.5%, respectively. At 90° of elbow flexion, the cutoff value for complete MUCL rupture was 1.0 mm (P < .001), with a sensitivity and specificity of 81.0% and 66.4%, respectively. CONCLUSION: Stress ultrasound can be used to diagnose complete MUCL tears in athletes when joint gapping is greater than 0.5 mm at 30° of elbow flexion and greater than 1 mm at 90° of elbow flexion.

Partial meniscectomy provides the favorable outcomes for symptomatic medial meniscus tear with an intact posterior root.

PURPOSE: This study aimed to investigate the long-term outcomes of arthroscopic partial meniscectomy for medial meniscus tear (with intact posterior root) and to analyze the risk factors for treatment failure. METHODS: The records of 165 patients who underwent partial meniscectomy for medial meniscus tear with intact posterior root with a minimum 5-year follow-up were included. Modified Lysholm score and radiologic outcomes were compared between preoperative and latest follow-up periods. The cumulative Outerbridge grade of the medial compartment was defined as follows: 0-4, low chondral wear; 5-6, intermediate wear; or 7-8, high wear. Kaplan-Meier survival and Cox hazard regression analyses were performed to assess the survivorship after partial meniscectomy. Conversion to total knee replacement arthroplasty, high tibial osteotomy or a Lysholm score of < 65 points indicated treatment failure. RESULTS: Mean Lysholm score improved from 66.3 ± 14.2 preoperatively to 81.8 ± 17.9 at the latest follow-up (p = 0.001). The postoperative 10-year survival rate of the low chondral wear group [97% (95% confidence interval (CI) 141.7-152.6 months)] was higher than that of the intermediate [83.1% (95% CI 129.6-147.9 months)] and high wear groups [76.1% (95% CI 115.2-135.0 months)]. A 1 mm joint space width narrowing led to a 37.7% increase in the failure rate [B = - 0.473; hazard ratio, 0.623 (95% CI 0.423-0.917); p = 0.016]. The high chondral wear group showed a higher failure rate compared to the low wear group [B = 1.870; hazard ratio, 6.488 (95% CI 0.853-49.333); p = 0.041]. CONCLUSION: Partial meniscectomy offers pain relief and functional improvement for medial meniscus tear with intact posterior root. Preoperative joint space narrowing and higher chondral wear at surgery were significant risk factors of treatment failure. Partial meniscectomy should be considered as an effective treatment for irreparable medial meniscus tear with intact posterior root without joint space narrowing and chondral wear. LEVEL OF EVIDENCE: Case series, Level IV.

CLINICAL OUTCOME OF POLYPOIDAL CHOROIDAL VASCULOPATHY/ANEURYSMAL TYPE 1 NEOVASCULARIZATION ACCORDING TO CHOROIDAL VASCULAR MORPHOLOGY.

PURPOSE: To determine the impact of choroidal vascular morphology on clinical outcomes in patients with polypoidal choroidal vasculopathy/aneurysmal Type 1 neovascularization. METHODS: Sixty-six eyes with polypoidal choroidal vasculopathy/aneurysmal Type 1 were included. Eyes were subdivided according to the choroidal vascular morphology of the large vessel layer on optical coherence tomography en face images: focal (n = 39) versus diffuse (n = 27) pachyvessels. All patients were treated with intravitreal ranibizumab pro re nata with or without rescue photodynamic therapy. RESULTS: Best-corrected visual acuity at baseline, 6, and 12 months did not differ between groups (P = 0.394, 0.142, and 0.292). At Month 3, best-corrected visual acuity was worse, and the proportion of eyes with fluid was higher in the focal group (P = 0.016 and 0.024). Among responders, the number of injections during 12-month follow-up was higher in the focal group (P = 0.033). During the total follow-up period, photodynamic therapy was required in 15 eyes (10 focal and 5 diffuse group, P = 0.497). The injection-free period after the photodynamic therapy was shorter in the focal group (P = 0.018). CONCLUSION: The polypoidal choroidal vasculopathy/aneurysmal Type 1 eyes with a diffuse pattern of pachyvessels required fewer injections during 12-month follow-up and showed a longer injection-free period after rescue photodynamic therapy.

Does anchor insertion angle or placement of the suture anchor affect glenoid rim fracture occurrence after arthroscopic Bankart repair?

BACKGROUND: The purposes were to compare the characteristics of 2 groups of patients who underwent revision Bankart repair with and without glenoid rim fractures and to examine risk factors for glenoid rim fractures. METHODS: We retrospectively analyzed 39 patients who needed revision surgery after arthroscopic Bankart repair and identified 19 patients with and 20 patients without glenoid rim fractures. The insertion angle of the suture anchor, anchor position on the glenoid, and demographic data were compared between the groups. RESULTS: The mean anchor insertion angles in the glenoid fracture group (group F) at the 2-, 3-, 4-, and 5-o'clock positions were 64°, 58°, 55°, and 55°, respectively; those in the no-fracture group (group R) were 60°, 63°, 60°, and 55°, respectively (P = .630, P = .207, P = .166, and P = .976, respectively). At the 5-o'clock position, anchors were fixed to the glenoid face in 13 cases in group F and in 3 cases in group R (P = .040). Although age (P = .529) and sex (P = 1.0) did not differ between the groups, elite and professional athletes had a significantly higher incidence of glenoid rim fractures (P = .009). CONCLUSION: The anchor insertion angle did not affect glenoid rim fracture occurrence after arthroscopic Bankart repair. However, the placement of the suture anchor at the 5-o'clock position on the glenoid face could increase the risk of glenoid rim fracture after trauma. Athletes were more likely to have glenoid rim fractures owing to major trauma after arthroscopic Bankart repair.

Omega-3 Polyunsaturated Fatty Acids Prevent Toxoplasma gondii Infection by Inducing Autophagy via AMPK Activation.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have potential protective activity in a variety of infectious diseases, but their actions and underlying mechanisms in Toxoplasma gondii infection remain poorly understood. Here, we report that docosahexaenoic acid (DHA) robustly induced autophagy in murine bone marrow-derived macrophages (BMDMs). Treatment of T. gondii-infected macrophages with DHA resulted in colocalization of Toxoplasma parasitophorous vacuoles with autophagosomes and reduced intracellular survival of T. gondii. The autophagic and anti-Toxoplasma effects induced by DHA were mediated by AMP-activated protein kinase (AMPK) signaling. Importantly, BMDMs isolated from Fat-1 transgenic mice, a well-known animal model capable of synthesizing ω3-PUFAs from ω6-PUFAs, showed increased activation of autophagy and AMPK, leading to reduced intracellular survival of T. gondii when compared with wild-type BMDMs. Moreover, Fat-1 transgenic mice exhibited lower cyst burden in the brain following infection with the avirulent strain ME49 than wild-type mice. Collectively, our results revealed mechanisms by which endogenous ω3-PUFAs and DHA control T. gondii infection and suggest that ω3-PUFAs might serve as therapeutic candidate to prevent toxoplasmosis and infection with other intracellular protozoan parasites.

Antibacterial effects of sodium tripolyphosphate against Porphyromonas species associated with periodontitis of companion animals.

Porphyromonas species are closely associated with companion animal periodontitis which is one of the most common diseases in dogs and cats and leads to serious systemic diseases if left untreated. In this study, we evaluated the antimicrobial effects and mode of action of sodium tripolyphosphate (polyP3, Na5P3O10), a food additive with proven safety, using three pathogenic Porphyromonas species. The minimum inhibitory concentrations (MICs) of polyP3 against Porphyromonas gulae, Porphyromonas cansulci, and Porphyromonas cangingivalis were between 500 and 750 mg/L. PolyP3 significantly decreased viable planktonic cells as well as bacterial biofilm formation, even at sub-MIC concentrations. PolyP3 caused bacterial membrane disruption and this effect was most prominent in P. cangingivalis, which was demonstrated by measuring the amount of nucleotide leakage from the cells. To further investigate the mode of action of polyP3, high-throughput whole-transcriptome sequencing was performed using P. gulae. Approximately 30% of the total genes of P. gulae were differentially expressed by polyP3 (> 4-fold, adjusted p value < 0.01). PolyP3 influenced the expression of the P. gulae genes related to the biosynthesis of thiamine, ubiquinone, and peptidoglycan. Collectively, polyP3 has excellent antibacterial effects against pathogenic Porphyromonas species and can be a promising agent to control oral pathogenic bacteria in companion animals.