A Novel mechanism of herbicide action through disruption of pyrimidine biosynthesis.

A lead aryl pyrrolidinone anilide identified using high-throughput in vivo screening was optimized for efficacy, crop safety, and weed spectrum, resulting in tetflupyrolimet. Known modes of action were ruled out through in vitro enzyme and in vivo plant-based assays. Genomic sequencing of aryl pyrrolidinone anilide-resistant Arabidopsis thaliana progeny combined with nutrient reversal experiments and metabolomic analyses confirmed that the molecular target of the chemistry was dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the fourth step in the de novo pyrimidine biosynthesis pathway. In vitro enzymatic and biophysical assays and a cocrystal structure with purified recombinant plant DHODH further confirmed this enzyme as the target site of this class of chemistry. Like known inhibitors of other DHODH orthologs, these molecules occupy the membrane-adjacent binding site of the electron acceptor ubiquinone. Identification of a new herbicidal chemical scaffold paired with a novel mode of action, the first such finding in over three decades, represents an important leap in combatting weed resistance and feeding a growing worldwide population.

Porphyran Attenuates Neuronal Loss in the Hippocampal CA1 Subregion Induced by Ischemia and Reperfusion in Gerbils by Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation.

Porphyran, a sulfated polysaccharide found in various species of marine red algae, has been demonstrated to exhibit diverse bioactivities, including anti-inflammatory effects. However, the protective effects of porphyran against cerebral ischemia and reperfusion (IR) injury have not been investigated. The aim of this study was to examine the neuroprotective effects of porphyran against brain IR injury and its underlying mechanisms using a gerbil model of transient forebrain ischemia (IR in the forebrain), which results in pyramidal cell (principal neuron) loss in the cornu ammonis 1 (CA1) subregion of the hippocampus on day 4 after IR. Porphyran (25 and 50 mg/kg) was orally administered daily for one week prior to IR. Pretreatment with 50 mg/kg of porphyran, but not 25 mg/kg, significantly attenuated locomotor hyperactivity and protected pyramidal cells located in the CA1 area from IR injury. The pretreatment with 50 mg/kg of porphyran significantly suppressed the IR-induced activation and proliferation of microglia in the CA1 subregion. Additionally, the pretreatment significantly inhibited the overexpressions of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing protein-3 (NLRP3) inflammasome complex, and pro-inflammatory cytokines (interleukin 1 beta and interleukin 18) induced by IR in the CA1 subregion. Overall, our findings suggest that porphyran exerts neuroprotective effects against brain IR injury, potentially by reducing the reaction (activation) and proliferation of microglia and reducing NLRP3 inflammasome-mediated neuroinflammation.

Postoperative Decrease in Bone Marrow Lesion Associated With Better Clinical Outcomes Following Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To assess serial changes of preoperative bone marrow lesion (BML) following medial open-wedge high tibial osteotomy (MOWHTO) up to 2 years and evaluate whether postoperative change of BML affected patient-reported outcome measures (PROMs) at 2 years' follow-up. Factors related to the postoperative changes in BML also were evaluated. METHODS: The current study retrospectively assessed prospectively collected data of consecutive patients between December 2016 and March 2018 who underwent MOWHTO for symptomatic knee osteoarthritis with varus malalignment (≥5°) and a minimum 2-year follow-up. Serial magnetic resonance imaging scans at preoperative and postoperative 3, 6, 18, and 24 months were performed, and the extent of BML was evaluated consecutively using 2 validated methods. Clinically, preoperative and postoperative PROMs and their achievement of minimal clinically important difference values were evaluated. The associations of the extent of BMLs with PROMs at each follow-up period over time were analyzed using a linear mixed model. Furthermore, factors related to the postoperative changes of BML were assessed. RESULTS: Of 26 patients, 21 (80.8%) had preoperative BML at medial femoral and tibial condyles. The postoperative decrease in BML was noted in 17 (81.0%) and 18 (85.7%) at medial femoral and tibial condyles. The BML decreased at postoperative 3 months and, thereafter, the extent of BML gradually reduced until postoperative 24 months. The proportion of patients achieved minimal clinically important difference was 84.6% for total Western Ontario and McMaster Universities Osteoarthritis Index scores and 80.8%, 76.9%, and 84.6% for KOOS symptom, pain, and activity of daily living subscales. Postoperative decrease in BML was significantly associated with better PROMs over postoperative 24 months. Furthermore, normo-correction (2°-5° valgus) was a significant factor for decreased BML following MOWHTO. CONCLUSIONS: Preoperative BML gradually decreased with time following MOWHTO, and the postoperative decrease in BML related with better PROMs over postoperative 24 months. Moreover, postoperative valgus alignment was a significant factor relating the postoperative decrease of BML. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Evaluation and Classification of Supraorbital Nerve Emerging Patterns.

BACKGROUND: Numerous significant variations in the supraorbital nerve (SON) pass through the notches and foramina. During endoscopic forehead lifting, the passage and the location of the nerve against the frontal bone render it susceptible to injury, resulting in diminished or absent sensation in the corresponding location. We attempted to obtain accurate knowledge of the SON emergence routes. METHODS: Data of patients who underwent an endoscopic forehead lift in a plastic surgery clinic between November 2015 and August 2021 were retrospectively analyzed. Deep and superficial branch pathways of SONs were identified and compared according to side and gender. We also classified the nerve patterns into six types. RESULTS: Altogether, 942 patients (1884 SON cases) were evaluated. Out of the patients, 86 patients were male, and 856 were female. The overall mean age was 48.6 (± 13.1) years. In the deep branches, 49% came from the notch, and 51% came from the foramen. In the superficial branches, 67% came from the notch, and 33% of superficial branches came from the foramen. Unlike the deep branch, superficial branches from the notch were significant. Deep and superficial branches of male patients were much more notched than those of female patients. Branches emerged together in 56% and separately in 44% of the cases. CONCLUSION: The absolute number of SON notches was higher than that of SON foramina. This study with the largest number of SON cases will help surgeons understand the variation and course of SON. LEVEL OF EVIDENCE IV: This journal requires that authors 38 assign a level of evidence to each article. For a full 39 description of these Evidence-Based Medicine ratings, 40 please refer to the Table of Contents or the online 41 Instructions to Authors www.springer.com/00266 .

Neuroprotective Effects of Aucubin against Cerebral Ischemia and Ischemia Injury through the Inhibition of the TLR4/NF-κB Inflammatory Signaling Pathway in Gerbils.

Aucubin, an iridoid glycoside, possesses beneficial bioactivities in many diseases, but little is known about its neuroprotective effects and mechanisms in brain ischemia and reperfusion (IR) injury. This study evaluated whether aucubin exhibited neuroprotective effects against IR injury in the hippocampal CA1 region through anti-inflammatory activity in gerbils. Aucubin (10 mg/kg) was administered intraperitoneally once a day for one week prior to IR. Neuroprotective effects of aucubin were assessed by neuronal nuclei (NeuN) immunofluorescence and Floro-Jade C (FJC) histofluorescence. Microgliosis and astrogliosis were evaluated using immunohistochemistry with anti-ionized calcium binding adapter protein 1 (Iba1) and glial fibrillary acidic protein (GFAP). Protein levels of proinflammatory cytokines interleukin1 beta (IL1ß) and tumor necrosis factor alpha (TNFα) were assayed using enzyme-linked immunosorbent assay and Western blot. Changes in toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway were assessed by measuring levels of TLR4, inhibitor of NF-κB alpha (IκBα), and NF-κB p65 using Western blot. Aucubin treatment protected pyramidal neurons from IR injury. IR-induced microgliosis and astrogliosis were suppressed by aucubin treatment. IR-induced increases in IL1ß and TNFα levels were significantly alleviated by the treatment. IR-induced upregulation of TLR4 and downregulation of IκBα were significantly prevented by aucubin treatment, and IR-induced nuclear translocation of NF-κB was reversed by aucubin treatment. Briefly, aucubin exhibited neuroprotective effects against brain IR injury, which might be related to the attenuation of neuroinflammation through inhibiting the TLR-4/NF-κB signaling pathway. These results suggest that aucubin pretreatment may be a potential approach for the protection of brain IR injury.

Engineering homoeologs provide a fine scale for quantitative traits in polyploid.

Numerous staple crops exhibit polyploidy and are difficult to genetically modify. However, recent advances in genome sequencing and editing have enabled polyploid genome engineering. The hexaploid black nightshade species Solanum nigrum has immense potential as a beneficial food supplement. We assembled its genome at the scaffold level. After functional annotations, we identified homoeologous gene sets, with similar sequence and expression profiles, based on comparative analyses of orthologous genes with close diploid relatives Solanum americanum and S. lycopersicum. Using CRISPR-Cas9-mediated mutagenesis, we generated various mutation combinations in homoeologous genes. Multiple mutants showed quantitative phenotypic changes based on the genotype, resulting in a broad-spectrum effect on the quantitative traits of hexaploid S. nigrum. Furthermore, we successfully improved the fruit productivity of Boranong, an orphan cultivar of S. nigrum suggesting that engineering homoeologous genes could be useful for agricultural improvement of polyploid crops.

Therapeutic Treatment with Pycnogenol® Attenuates Ischemic Brain Injury in Gerbils Focusing on Cognitive Impairment, Neuronal Death, BBB Leakage and Neuroinflammation in the Hippocampus.

BACKGROUND: A gerbil model of ischemia and reperfusion (IR) injury in the forebrain has been developed for studies on mechanisms, prevention and therapeutic strategies of IR injury in the forebrain. Pycnogenol® (PYC), a standardized extract of French maritime pine tree (Pinus pinaster Aiton) has been exploited as an additive for dietary supplement. In the present study, we investigated the neuroprotective effects of post-treatment with PYC and its therapeutic mechanisms in gerbils. METHODS: The gerbils were given sham and IR operation and intraperitoneally injected with vehicle and Pycnogenol® (25, 50 and 100 mg/kg, respectively) immediately, at 24 hours and 48 hours after sham and IR operation. Through 8-arm radial maze test and passive avoidance test, each spatial memory and short-term memory function was assessed. To examine the neuroprotection of Pycnogenol®, we conducted cresyl violet staining, immunohistochemistry for neuronal nuclei, and Fluoro-Jade B histofluorescence. Moreover, we carried out immunohistochemistry for immunoglobulin G (IgG) to investigate blood-brain barrier (BBB) leakage and interleukin-1ß (IL-1ß) to examine change in pro-inflammatory cytokine. RESULTS: We found that IR-induced memory deficits were significantly ameliorated when 100 mg/kg Pycnogenol® was treated. In addition, treatment with 100 mg/kg Pycnogenol®, not 25 mg/kg nor 50 mg/kg, conferred neuroprotective effect against IR injury. For its mechanisms, we found that 100 mg/kg Pycnogenol® significantly reduced BBB leakage and inhibited the expression of IL-1ß. CONCLUSIONS: Therapeutic treatment (post-treatment) with Pycnogenol® after IR effectively attenuated ischemic brain injury in gerbils. Based on these results, we suggest that PYC can be employed as an important material for ischemic drugs.

Closed-wedge high tibial osteotomy is more advantageous to maintain the correction than open-wedge high tibial osteotomy in osteopenic patients.

PURPOSE: To compare the incidence of correction loss and survival rate between closed-wedge and open-wedge high tibial osteotomies (CWHTO and OWHTO, respectively) in patients with osteopenic and normal bone. METHODS: Retrospective review was conducted for 115 CWHTOs and 119 OWHTOs performed in osteopenic patients [- 2.5 < Bone mineral density (BMD) T scores ≤ - 1] and 136 CWHTOs and 138 OWHTOs performed in normal patients (BMD T score > - 1) from 2012 to 2019. Demographics were not different between CW- and OWHTOs in osteopenic and normal patients (n.s., respectively). Radiographically, the mechanical axis (MA), medial proximal tibial angle (MPTA), and posterior tibial slope (PTS) were evaluated pre- and postoperatively (2 weeks after HTO). The occurrence of hinge fractures was investigated using radiographs taken on the operation day. The correction change was calculated as the last follow-up value minus postoperative MPTA. Correction loss was defined when the correction change was ≥ 3°. The survival rate (failure: correction loss) was investigated. RESULTS: There were no significant differences in the pre and postoperative MA, MPTA, PTS, and value changes between CW- and OWHTOs in osteopenic and normal patients (n.s., respectively); the incidence of unstable hinge fractures also did not differ significantly (CWHTO vs. OWHTO = 7 vs. 7.6% in osteopenic patients; 2.9 vs. 3.6% in normal patients; n.s., respectively). The average correction change (CWHTO = - 0.6°, OWHTO = - 1.3°, p = 0.007), incidence of correction loss (CWHTO = 1.7%, OWHTO = 9.2%, p = 0.019), and 5-year survival rates (CWHTO = 98.3%, OWHTO = 90.8%, p = 0.013) differed significantly in osteopenic patients; there were no significant differences in these results in normal patients (n.s., respectively). CONCLUSION: CWHTO was more advantageous than OWHTO regarding the correction loss in osteopenic patients. Intra- and postoperative care that consider poor bone quality will be required when performing OWHTOs in osteopenic patients. LEVEL OF EVIDENCE: III.

Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice.

Osteoporosis is evident in postmenopausal women and is an osteolytic disease characterized by bone loss that further increases the susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. Edible Cirsium setidens contains various polyphenols of linarin, pectolinarin, and apigenin with antioxidant and hepatoprotective effects. This study aimed to determine whether Cirsium setidens water extracts (CSEs), the component linarin, and its aglycone acacetin blocked ovariectomy (OVX)-induced bone loss. This study employed OVX C57BL/6 female mice as a model for postmenopausal osteoporosis. CSEs, acacetin, or linarin was orally administrated to OVX mice at a dose of 20 mg/kg for 8 weeks. Surgical estrogen loss in mice for 8 weeks reduced bone mineral density (BMD) of mouse femur and serum 17ß-estradiol level and enhanced the serum receptor activator of NF-κB ligand/osteoprotegerin ratio with uterine atrophy. CSEs and linarin reversed such adverse effects and enhanced femoral BMD in OVX mice. Oral administration of CSEs and linarin attenuated tartrate-resistant acid phosphate activity and the induction of αvß3 integrins and proton suppliers in resorption lacunae in femoral bone tissue of OVX mice. In addition, CSEs and linarin curtailed the bone levels of cathepsin K and matrix metalloproteinase-9 responsible for osteoclastic bone resorption. On the other hand, CSEs and linarin enhanced the formation of trabecular bones in estrogen-deficient femur with increased induction of osteocalcin and osteopontin. Further, treatment with CSEs and linarin enhanced the collagen formation-responsive propeptide levels in the circulation along with the increase in the tissue non-specific alkaline phosphatase level in bone exposed to OVX. Supplementing CSEs, acacetin, or linarin to OVX mice elevated the formation of collagen fibers in OVX trabecular bone, evidenced using Picrosirius red staining. Accordingly, CSEs and linarin were effective in retarding osteoclastic bone resorption and promoting osteoblastic bone matrix mineralization under OVX conditions. Therefore, linarin, which is abundant in CSEs, may be a natural compound for targeting postmenopausal osteoporosis and pathological osteoresorptive disorders.

Inhibitory Effects of Loganin on Adipogenesis In Vitro and In Vivo.

Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) in vitro and in mice with ovariectomy (OVX)- and high-fat diet (HFD)-induced obesity in vivo. For an in vitro study, loganin was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs, lipid droplets were evaluated by oil red O staining, and adipogenesis-related factors were assessed by qRT-PCR. For in vivo studies, mouse models of OVX- and HFD-induced obesity were orally administered with loganin, body weight was measured, and hepatic steatosis and development of excessive fat were evaluated by histological analysis. Loganin treatment reduced adipocyte differentiation by accumulating lipid droplets through the downregulation of adipogenesis-related factors, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), perilipin 2 (Plin2), fatty acid synthase (Fasn), and sterol regulatory element binding transcription protein 1 (Srebp1). Loganin administration prevented weight gain in mouse models of obesity induced by OVX and HFD. Further, loganin inhibited metabolic abnormalities, such as hepatic steatosis and adipocyte enlargement, and increased the serum levels of leptin and insulin in both OVX- and HFD-induced obesity models. These results suggest that loganin is a potential candidate for preventing and treating obesity.

Radiologic findings associated with mucoid degeneration of the anterior cruciate ligament.

INTRODUCTION: Mucoid degeneration (MD) of the anterior cruciate ligament (ACL) is a well-recognized pathology characterized by the degradation of collagen fibers and infiltration of a mucoid-like substance. This study is to determine the anatomical associated factors for MD-ACL using radiographic and magnetic resonance imaging (MRI). MATERIALS AND METHODS: This was a retrospective study on patients who had undergone knee arthroscopy between 2011 and 2020. The patients with MD-ACL were defined and enrolled by the MRI and arthroscopy. Eventually, 52 patients in the MD-ACL group (group 1) and 52 patients in the control group (group 2) were enrolled, following sex and age matching. Radiologic evaluation included the assessment of Kellgren-Lawrence (K-L) grade, mechanical hip-knee-ankle (HKA) angle, posterior tibial slope (PTS) angle, and Insall-Salvati ratio. The notch width index and transverse notch angle were measured on MRI, and the grade of trochlear dysplasia was defined. Logistic regression analysis, receiver operating characteristic (ROC) curves, and area under curve (AUC) were performed. RESULTS: The ROM was significantly decreased in group 1, whereas the PTS angle was significantly larger in group 1. Combined ganglion cysts of ACL were found in 42/52 patients (80.7%) in group 1. The risk of MD-ACL was associated with a steeper PTS angle, increased Insall-Salvati ratio, male sex, higher K-L grade, and decreased transverse notch angle and notch width index. The cutoff values in ROC analysis were found to be ≤ 28.27% for the notch width index (AUC, 0.849; p < 0.001), > 12.2° for the PTS angle (AUC, 0.765; p < 0.001), and ≤ 47.4° for the transverse notch angle (AUC, 0.711; p < 0.001), but not significant for Insall-salvati ratio. CONCLUSION: A steeper PTS angle, decreased notch width index, and transverse notch angle are significantly associated with the presence of MD-ACL. These factors should be considered during diagnosis or when determining the treatment strategy for symptomatic MD-ACL patients. LEVEL OF EVIDENCE: Level IIIb.

Association between Pneumonia Development and Virulence Gene Expression in Carbapenem-Resistant Acinetobacter baumannii Isolated from Clinical Specimens.

We investigated the virulence gene expression of carbapenem-resistant Acinetobacter baumanii (CRAB) isolated from the respiratory samples of patients with CRAB pneumonia and those with CRAB colonization to identify the virulence genes contributing to CRAB pneumonia's development and mortality. Patients with CRAB identified from respiratory specimens were screened at a tertiary university hospital between January 2018 and January 2019. Patients were classified into CRAB pneumonia or CRAB colonization groups according to predefined clinical criteria. A. baumannii isolated from respiratory specimens was examined for the expression levels of ompA, uspA, hfq, hisF, feoA, and bfnL by quantitative reverse-transcription polymerase chain reaction. Among 156 patients with CRAB from respiratory specimens, 17 and 24 met the criteria for inclusion in the pneumonia and colonization groups, respectively. The expression level of ompA was significantly higher in the pneumonia group than in the colonization group (1.45 vs. 0.63, P=0.03). The expression levels of ompA (1.97 vs. 0.86, P=0.02), hisF (1.06 vs. 0.10, P < 0.01), uspA (1.62 vs. 1.01, P < 0.01), and bfnL (3.14 vs. 2.14, P=0.03) were significantly higher in patients with 30-day mortality than in the surviving patients. Elevated expression of hisF (adjusted odds ratio = 5.93, P=0.03) and uspA (adjusted odds ratio = 7.36, P=0.02) were associated with 30-day mortality after adjusting for age and the Charlson score. uspA and hisF may serve as putative targets for novel therapeutic strategies.

Risk factors for increased perioperative blood loss during total knee arthroplasty in patients with haemophilia.

INTRODUCTION: Currently, there is a paucity of literature describing the risk factors for increased perioperative blood loss (PBL) during total knee arthroplasty (TKA) in haemophilia. Furthermore, no studies have analysed coagulation factor levels that affect PBL. AIM: To identify the risk factors for increased PBL by incorporating coagulation factor levels following TKA in patients with haemophilic arthropathy. METHODS: A total of 92 TKA (78 haemophilia A and 14 haemophilia B) were performed for haemophilic arthropathy. PBL was calculated using the haemoglobin (Hb) balance method, and patients were categorised into two groups: group H (higher blood loss than the mean PBL, n = 36) and group L (lower blood loss than the mean PBL, n = 56). Body mass index (BMI), operation day Hb, haematocrit and coagulation factor level (VIII or IX) were analysed, including demographic and laboratory data. RESULTS: The mean PBL volume during TKA for haemophilic arthropathy of the knee was 542.3 ± 361.7 mL. Multivariate analysis revealed that lower haematocrit on the operation day (odds ratio [OR], .633; 95% confidence interval [CI], .511-.786; p < .001) and coagulation factor level (OR .970, CI .941-.999; p = .046) were independent risk factors for increased PBL. Receiver-operating characteristic analysis identified these cutoff values for predicting increased PBL: operation day coagulation factor level 93.5% (sensitivity, 70.4%; specificity, 67.6%) and haematocrit level of 38.2% (sensitivity, 85.7%; specificity, 80.6%). CONCLUSIONS: The PBL increased as haematocrit and coagulation factor levels decreased on the operation day. A coagulation factor level <93.5% or haematocrit level of <38.2% may be a significant risk factor for increasing PBL. LEVEL OF EVIDENCE: Level IV, Case Series, Treatment Study.

Protective Effects of Topical Administration of Laminarin in Oxazolone-Induced Atopic Dermatitis-like Skin Lesions.

Laminarin is a polysaccharide isolated from brown marine algae and has a wide range of bioactivities, including immunoregulatory and anti-inflammatory properties. However, the effects of laminarin on atopic dermatitis have not been demonstrated. This study investigated the potential effects of topical administration of laminarin using a Balb/c mouse model of oxazolone-induced atopic dermatitis-like skin lesions. Our results showed that topical administration of laminarin to the ear of the mice improved the severity of the dermatitis, including swelling. Histological analysis revealed that topical laminarin significantly decreased the thickening of the epidermis and dermis and the infiltration of mast cells in the skin lesion. Serum immunoglobulin E levels were also significantly decreased by topical laminarin. Additionally, topical laminarin significantly suppressed protein levels of oxazolone-induced proinflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α in the skin lesion. These results indicate that topical administration of laminarin can alleviate oxazolone-induced atopic dermatitis by inhibiting hyperproduction of IgE, mast cell infiltration, and expressions of proinflammatory cytokines. Based on these findings, we propose that laminarin can be a useful candidate for the treatment of atopic dermatitis.

Serial Improvement of Medial Meniscus Extrusion Following Medial Open-Wedge High Tibial Osteotomy Does Not Correlate With Clinical Outcomes and Arthroscopic Articular Cartilage Improvement.

PURPOSE: To assess serial change up to 2 years in medial meniscus extrusion (MME) following medial open-wedge high tibial osteotomy (MOWHTO) and to determine whether postoperative changes in MME correlated with clinical outcomes and arthroscopic articular cartilage status. METHODS: This study included 26 patients from December 2016 to March 2018 who underwent MOWHTO for primary medial osteoarthritis with varus malalignment. Second-look arthroscopy with plate removal was performed at postoperative 2 years. MME was consecutively measured using coronal magnetic resonance imaging at preoperative and postoperative 3 months, 6 months, 1.5 years, and 2 years. We also assessed which preoperative parameters could reflect the postoperative changes in MME and evaluated whether postoperative clinical outcomes and arthroscopic articular cartilage improvement would be influenced by the MME changes. RESULTS: Regarding the postoperative serial changes in MME values, significant improvement in MME was noted from postoperative 6 months (P = .003), and thereafter, mean MME was further improved with time until postoperative 2 years (P < .001). Regarding the correlation between preoperative parameters and MME changes, preoperative medial proximal tibial angle (MPTA) showed significant correlations in univariate and multivariate analysis (P = .004 and P = .004, respectively). Meanwhile, changes in MME were not correlated with postoperative clinical outcomes or arthroscopic articular cartilage improvement. CONCLUSION: After MOWHTO, MME improved with time and was significantly correlated with preoperative MPTA. However, the changes in MME after MOWHTO did not reflect postoperative clinical and arthroscopic articular cartilage improvement. LEVEL OF EVIDENCE: IV, case series.

Steep posterior lateral tibial slope, bone contusion on lateral compartments and combined medial collateral ligament injury are associated with the increased risk of lateral meniscal tear.

PURPOSE: To determine the risk factors for lateral meniscus and root tears in patients with acute anterior cruciate ligament (ACL) injuries. METHODS: A total of 226 patients undergoing acute ACL reconstruction were included in the study sample. Exclusion criteria were revisions, fractures, chronic cases, and multiple ligament injuries, with the exception of medial collateral ligament (MCL) injuries. The patients were divided into groups based on the presence of lateral meniscus and root tears by arthroscopy. Binary logistic regression was used to analyze risk factors including age, sex, body mass index (BMI), injury mechanism (contact/non-contact), Segond fracture, side-to-side laxity, location of bone contusion, medial and lateral tibial and meniscal slope, mechanical axis angle, and grade of pivot shift. RESULTS: Overall lateral meniscus (LM) tears were identified in 97 patients (42.9%), and LM root tears were found in 22 patients (9.7%). The risk of an LM tear in ACL-injured knees increased with bone contusion on LTP (odds ratio [OR], 3.5; 95% confidence interval [CI] 1.419-8.634; P = 0.007), steeper lateral tibial slope (OR, 1.133; 95% CI 1.003-1.28; P = 0.045), MCL injury (OR, 2.618; 95% CI 1.444-4.746; P = 0.002), and non-contact injury mechanism (OR, 3.132; 95% CI 1.446-6.785; P = 0.004) in logistic regression analysis. The risk of LM root tear in ACL-injured knees increased with high-grade pivot shift (OR, 9.127; 95% CI 2.821-29.525; P = 0.000) and steeper lateral tibial slope (OR, 1.293; 95% CI 1.061-1.576; P = 0.011). CONCLUSION: The increased risk of LM lesions in acute ACL-injured knees should be considered if significant risk factors including bone contusion on lateral compartments, MCL injury, and a steeper lateral tibial slope are present. Moreover, high-grade rotational injury with steeper lateral tibial slope are also significant risk factors for LM root tears, and therefore care should be taken by clinicians not to miss such lesions. LEVEL OF EVIDENCE: III.

New Classification for Periprosthetic Distal Femoral Fractures Based on Locked-Plate Fixation Following Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: This study aimed to establish a new classification using locked-plate fixation for periprosthetic distal femoral fracture (PDFF) following total knee arthroplasty (TKA) and to determine when dual locked-plate fixation is necessary through defining this classification. METHODS: One-hundred fifteen consecutive PDFFs that underwent operative treatment were reviewed from 2011 to 2019 with minimum 1-year follow-up. Most PDFFs were fixed with single or dual locked-plate fixations using the minimally invasive plate osteosynthesis technique. Based on preoperative radiographs, PDFFs were classified according to the level of main fracture line relative to the anterior flange of femoral component: type I and II, main fracture line located proximal and distal to the anterior flange; and type III, component instability regardless of fracture line requiring revisional TKA. Furthermore, type II fractures were subclassified based on the direction of fracture beak as follows: type IIL, lateral-beak; type IIM, medial-beak. The incidence, treatment methods, and complications were analyzed according to the classification. RESULTS: Incidences of type I, IIL, IIM, and III were 64.4%, 8.7%, 24.3%, and 2.6%, respectively. Meanwhile, most PDFFs in type I and II were treated with lateral single locked-plate fixations, except for type IIM, which was treated with either single or dual locked-plate fixations. Overall complications were significantly higher in type II (28.9%) than in type I (10.8%, P = .019). In type IIM, bone union-related complications were significantly higher in single locked-plate fixation (50.0%) than in dual locked-plate fixation (5.6%; P = .013). CONCLUSION: The new classification provides practical and obvious strategies for the treatment of PDFF following TKA using locked-plate fixation. For type IIM fracture, dual plate fixation is necessary to prevent fixation failure or nonunion.

The Effect of the Back-Pressure Changes in an Exhaust System on Vibration When Attaching a Variable Device during Idling.

The vibration of the ignition frequency component of the engine during idling causes driver discomfort. To minimize this, an optimal exhaust system with a variable device that can exert optimal pressure is required. In this study, the geometry of the variable device was designed in orifice and cylinder types. Next, the designed variable devices were implemented in a conventional exhaust system with an X chamber. A comparative analysis was conducted to propose an optimal geometry through back-pressure and vibration measurements. During the experiment, the orifice geometry exhibited higher back pressure than the conventional geometry and a large difference in back pressure before and at the exhaust gas merging position. Furthermore, the orifice geometry showed a 2.56% increase in the vibration of the 1X component in the Y-axis direction. By contrast, the cylinder geometry exhibited slightly higher back pressure than the conventional geometry and the smallest difference in back pressure before and at the exhaust gas merging position. The cylinder geometry showed a 2.45% reduction in the vibration of the 1X component in the Y-axis direction.

Relationship between Neuronal Damage/Death and Astrogliosis in the Cerebral Motor Cortex of Gerbil Models of Mild and Severe Ischemia and Reperfusion Injury.

Neuronal loss (death) occurs selectively in vulnerable brain regions after ischemic insults. Astrogliosis is accompanied by neuronal death. It can change the molecular expression and morphology of astrocytes following ischemic insults. However, little is known about cerebral ischemia and reperfusion injury that can variously lead to damage of astrocytes according to the degree of ischemic injury, which is related to neuronal damage/death. Thus, the purpose of this study was to examine the relationship between damage to cortical neurons and astrocytes using gerbil models of mild and severe transient forebrain ischemia induced by blocking the blood supply to the forebrain for five or 15 min. Significant ischemia tFI-induced neuronal death occurred in the deep layers (layers V and VI) of the motor cortex: neuronal death occurred earlier and more severely in gerbils with severe ischemia than in gerbils with mild ischemia. Distinct astrogliosis was detected in layers V and VI. It gradually increased with time after both ischemiae. The astrogliosis was significantly higher in severe ischemia than in mild ischemia. The ischemia-induced increase of glial fibrillary acidic protein (GFAP; a maker of astrocyte) expression in severe ischemia was significantly higher than that in mild ischemia. However, GFAP-immunoreactive astrocytes were apparently damaged two days after both ischemiae. At five days after ischemiae, astrocyte endfeet around capillary endothelial cells were severely ruptured. They were more severely ruptured by severe ischemia than by mild ischemia. However, the number of astrocytes stained with S100 was significantly higher in severe ischemia than in mild ischemia. These results indicate that the degree of astrogliosis, including the disruption (loss) of astrocyte endfeet following ischemia and reperfusion in the forebrain, might depend on the severity of ischemia and that the degree of ischemia-induced neuronal damage may be associated with the degree of astrogliosis.

Effects of Loganin on Bone Formation and Resorption In Vitro and In Vivo.

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast-osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.