Cross-Species Metabolomic Analyses in the Brassicaceae Reveals Common Responses to Ultraviolet-B Exposure.

Exposure to UV-B radiation, an intrinsic component of solar light, is detrimental to all living organisms as chromophore units of DNA, RNA and proteins readily absorb high-energy photons. Indirect damage to the same molecules and lipids is mediated by elevated reactive oxygen species (ROS) levels, a side effect of exposure to UV-B stress. To protect themselves from UV-B radiation, plants produce phytochemical sunscreens, among which flavonoids have shown to be particularly effective. The core aglycone of flavonoid molecules is subjected to chemical decoration, such as glycosylation and acylation, further improving sunscreen properties. In particular, acylation, which adds a phenolic ring to flavonoid molecules, enhances the spectral absorption of UV-A and UV-B rays, providing to this class of compounds exceptional shielding power. In this study, we comprehensively analyzed the responses to UV-B radiation in four Brassicaceae species, including Arabidopsis thaliana, Brassica napus, Brassica oleracea, and Brassica rapa. Our study revealed a complete reprogramming of the central metabolic pathway in response to UV-B radiation characterized by increased production of functional precursors of specialized metabolites with UV-B shielding properties, indicating a targeted effort of plant metabolism to provide increased protection. The analysis of specialized metabolites and transcripts revealed the activation of the phenylpropanoid-acetate pathway, leading to the production of specific classes of flavonoids and a cross-species increase in phenylacylated-flavonoid glucosides with synapoyl glycoside decorations. Interestingly, our analysis also revealed that acyltransferase genes of the class of serine carboxypeptidase-like (SCPLs) proteins are costitutively expressed, but downregulated in response to UV-B radiation, possibly independently of the ELONGATED HYPOCOTYL 5 (HY5) signaling pathway.

Species-specific 'specialized' genomic region provides the new insights into the functional genomics characterizing metabolic polymorphisms in plants.

Functional genomics approaches with comparative omics analyses of wild-accessions and cultivars/wild species, as well as comparative genomic analyses in plant species focusing on gene clusters, have successfully detected key metabolic polymorphisms in plant specialized metabolism. In recent decades, (i) intra-species specific metabolic polymorphisms, (ii) new functionalization of tandem duplicated genes, and (iii) metabolic gene clusters were found as the main factors creating metabolic diversity of specialized metabolites in plants. However, given findings aware us that the identification of genes in plant specialized metabolism requires strategic approaches depending on the target metabolic pathways. The increasing availability of plant genome sequences and transcriptome data has facilitated inter-specific comparative analyses, including genomic analysis and gene co-expression network analysis. Here, we introduce functional genomics approaches with the integration of inter-/intra-species comparative metabolomics, their key roles in providing genomic signatures of metabolic evolution, and discuss future prospects of functional genomics on plant specialized metabolism.

Arabidopsis BBX14 negatively regulates nitrogen starvation- and dark-induced leaf senescence.

Senescence is a highly regulated process driven by developmental age and environmental factors. Although leaf senescence is accelerated by nitrogen (N) deficiency, the underlying physiological and molecular mechanisms are largely unknown. Here, we reveal that BBX14, a previously uncharacterized BBX-type transcription factor in Arabidopsis, is crucial for N starvation-induced leaf senescence. We find that inhibiting BBX14 by artificial miRNA (amiRNA) accelerates senescence during N starvation and in darkness, while BBX14 overexpression (BBX14-OX) delays it, identifying BBX14 as a negative regulator of N starvation- and dark-induced senescence. During N starvation, nitrate and amino acids like glutamic acid, glutamine, aspartic acid, and asparagine were highly retained in BBX14-OX leaves compared to the wild type. Transcriptome analysis showed a large number of senescence-associated genes (SAGs) to be differentially expressed between BBX14-OX and wild-type plants, including ETHYLENE INSENSITIVE3 (EIN3) which regulates N signaling and leaf senescence. Chromatin immunoprecipitation (ChIP) showed that BBX14 directly regulates EIN3 transcription. Furthermore, we revealed the upstream transcriptional cascade of BBX14. By yeast one-hybrid screen and ChIP, we found that MYB44, a stress-responsive MYB transcription factor, directly binds to the promoter of BBX14 and activates its expression. In addition, Phytochrome Interacting Factor 4 (PIF4) binds to the promoter of BBX14 to repress BBX14 transcription. Thus, BBX14 functions as a negative regulator of N starvation-induced senescence through EIN3 and is directly regulated by PIF4 and MYB44.

Internal Rotation, Varus, and Anterior Femoral Component Malalignments Adversely Affect Patellofemoral Joint Kinematics in Patellofemoral Arthroplasty.

Background: Patellofemoral arthroplasty (PFA) is reported to provide nearly normal PF joint kinematics but only with adequate surgical techniques. This study evaluated the effects of various femoral component settings on patellar component biomechanics. Methods: A dynamic musculoskeletal computer simulation analyzed normal knee and standard PFA models, as well as 8 femoral component malposition models: 5° internal or external rotation, 5° valgus or varus, 5° extension or flexion, and 3-mm or 5-mm anterior positioning. Mediolateral patellar translation, lateral patellar tilt, and contact force and stress at the PF joint were measured in each model during gait. Results: The patella in the standard PFA model was shifted up to 5.0 mm laterally near heel off and was tilted up to 3.0° laterally at heel strike compared to the normal knee model. The patella in the external rotation model translated more laterally in the direction of the femoral component setting than in the standard model. However, in the internal rotation and varus alignment models, the patellar lateral shift occurred largely in the opposite direction of the femoral component setting. The patella in most models was tilted in the same direction as the femoral component setting. The PF contact force was increased, especially in the anterior femoral position models, by up to 30 MPa compared with 20 MPa in the standard model. Conclusions: Internal rotation, varus, and anterior femoral component settings during PFA should be avoided to reduce postoperative complications, whereas external rotation might be appropriate only for cases with lateral patellar instability.

What is the Optimal Posterior Cruciate Ligament Tension to Achieve Patient Satisfaction in Cruciate-Retaining Total Knee Arthroplasty?

INTRODUCTION: Achieving adequate posterior cruciate ligament (PCL) tension is important during PCL-retaining total knee arthroplasty (CR-TKA), but the effect of PCL release on this tension is unpredictable. This study assessed the relationship between postoperative PCL laxity and patient satisfaction at a 2-year follow-up. METHODS: There were 44 varus osteoarthritis knees undergoing CR-TKA included. The PCL tension was adjusted by resizing the femoral component and modifying the posterior tibial slope, without PCL release. Postoperative PCL laxity at 90° of knee flexion was defined as the difference in radiographic anterior-posterior tibial translation with or without an 80-Newton posterior load at the tibial tubercle measured using a load device. Four subgroups were defined according to the PCL laxity: laxity ≤0 mm (n = 5); 0 mm < laxity ≤2 mm (n = 19); 2 mm < laxity ≤4 mm (n = 10); and laxity >4 mm (n = 10). The effect of PCL laxity on the 2-year postoperative 2011 Knee Society Score was determined. RESULTS: The femoral component was downsized in 27 of 44 knees, while the posterior tibia slope was increased in 6 of 44 knees, but no PCL was released intraoperatively. The 2011 Knee Society Score subscores improved significantly from preoperatively to postoperatively, and patients reported "neutral satisfaction" or better after 96% of operations. The mean PCL laxity was 2.3 mm on postoperative stress radiographs, and postoperative satisfaction scores were significantly highest in the subgroup with 2-4 mm laxity. CONCLUSION: CR-TKA was successfully performed without PCL release. Moderate PCL laxity (2-4 mm) achieved excellent postoperative satisfaction.

Anteromedial Tibial Attachment in Single-Bundle Anterior Cruciate Ligament Reconstruction Can Represent Normal Kinematics in Computer Simulation.

Tunnel position during anterior cruciate ligament (ACL) reconstruction is considered as an important factor to restore normal knee kinematics and to gain better clinical outcomes. It is still unknown where the optimal femoral and tibial tunnel position is located in single-bundle (SB) ACL reconstruction. The purposes of this study were to analyze the knee kinematics with various graft positions and to propose the optimal graft position during SB ACL reconstruction. A musculoskeletal computer simulation was used to analyze knee kinematics. Four attachments on the femoral side (anteromedial [AM], mid, posterolateral [PL], and over-the-top positions) and three attachments on the tibial side (AM, middle, and PL positions) were determined. The middle-bundle attachment was placed at the midpoint of the AM and PL bundle attachments for the femoral and tibial attachments. SB ACL reconstruction models were constructed to combine each of the four femoral attachments with each of three tibial attachments. Kinematic comparison was made among a double-bundle (DB) model and 12 SB reconstruction models during deep knee bend and stair descent activity. The tunnel position of the tibia had greater effect of knee kinematics than that of the femur. AM tibial attachment models showed similar medial and lateral anteroposterior positions to the DB model for both activities. Axial rotation in the AM tibial attachment models was similar to the DB model regardless of the femoral attachment, whereas greater maximum axial rotation was exhibited in the PL tibial attachment models, especially during stair descent activity. AM tibial attachment can represent normal knee kinematics, whereas the PL tibial attachment can induce residual rotational instability during high-demand activities. The AM tibial tunnel is recommended for SB ACL reconstruction.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

Patellar medial-lateral position can be used to correct the effect of leg rotation on preoperative planning in total knee arthroplasty for varus knees.

BACKGROUND: Lower limb malrotations can be observed in long leg radiographs, affecting the measurement of the angle between the mechanical and anatomical axes. The purposes were to analyze the effect of limb rotation and to evaluate the accuracy of the corrected angle between the mechanical and anatomical axes based on the patellar ML position. HYPOTHESIS: The hypothesis was that the correction of the angle between the mechanical and anatomical axes according to the patellar ML position can reduce the error from the angle in the true AP view in most of the knees. PATIENTS AND METHODS: A total of 100 consecutive knees with varus deformity undergoing primary total knee arthroplasty were included. Computed tomography images were digitally reconstructed in the neutral position, and internally and externally rotated at 10° and 20°, respectively. The patellar ML position relative to the medial (0%) and lateral (100%) epicondyles and the angle between the mechanical and anatomical axes of the femur were measured. The corrected angle between the mechanical and anatomical axes was calculated using the averaged translational ratio. RESULTS: In the neutral position, the patellar center position was 56.1% (standard deviation [SD]=4.7%), which was 31.4% (SD=7.2%) and 80.2% (SD=5.4%) in the 20° internal and external rotation, respectively. The angle between the mechanical and anatomical axes was 2.6° (SD=2.0°) and 8.1° (SD=2.1°) in the 20° internal and external rotation, respectively. On average, if the patellar center shifted 10%, the change of the angle between the mechanical and anatomical axes of the femur was 1.13°. Applying the corrected angle, a discrepancy from the neutral position decreased. CONCLUSION: The method to correct the angle between the mechanical and anatomical axes according to the patellar ML position can be used to reduce the measurement error for preoperative planning using a long leg radiograph. LEVEL OF EVIDENCE: III.

Sulfur deficiency-induced genes affect seed protein accumulation and composition under sulfate deprivation.

Sulfur deficiency-induced proteins SDI1 and SDI2 play a fundamental role in sulfur homeostasis under sulfate-deprived conditions (-S) by downregulating glucosinolates. Here, we identified that besides glucosinolate regulation under -S, SDI1 downregulates another sulfur pool, the S-rich 2S seed storage proteins in Arabidopsis (Arabidopsis thaliana) seeds. We identified that MYB28 directly regulates 2S seed storage proteins by binding to the At2S4 promoter. We also showed that SDI1 downregulates 2S seed storage proteins by forming a ternary protein complex with MYB28 and MYC2, another transcription factor involved in the regulation of seed storage proteins. These findings have significant implications for the understanding of plant responses to sulfur deficiency.

[A Study on Radiation Dermatitis Grading Support System Based on Deep Learning by Hybrid Generation Method].

PURPOSE: Radiation dermatitis is one of the most common adverse events in patients undergoing radiotherapy. However, the objective evaluation of this condition is difficult to provide because the clinical evaluation of radiation dermatitis is made by visual assessment based on Common Terminology Criteria for Adverse Events (CTCAE). Therefore, we created a radiation dermatitis grading support system (RDGS) using a deep convolutional neural network (DCNN) and then evaluated the effectiveness of the RDGS. METHODS: The DCNN was trained with a dataset that comprised 647 clinical skin images graded with radiation dermatitis (Grades 1-4) at our center from April 2011 to May 2019. We created the datasets by mixing data augmentation images generated by image conversion and images generated by Poisson image editing using the hybrid generation method (Hyb) against lowvolume severe dermatitis (Grade 4). We then evaluated the classification accuracy of RDGS based on the hybrid generation method (Hyb-RDGS). RESULTS: The overall accuracy of the Hyb-RDGS was 85.1%, which was higher than that of the data augmentation method generally used for image generation. CONCLUSION: Effectiveness of the Hyb-RDGS using Poisson image editing was suggested. This result shows a possible supporting system for objective evaluation in grading radiation dermatitis.

Assessing Dynamic Changes of Taste-Related Primary Metabolism During Ripening of Durian Pulp Using Metabolomic and Transcriptomic Analyses.

Durian is an economically important fruit of Southeast Asia. There is, however, a lack of in-depth information on the alteration of its metabolic networks during ripening. Here, we annotated 94 ripening-associated metabolites from the pulp of durian cv. Monthong fruit at unripe and ripe stages, using capillary electrophoresis- and gas chromatography- time-of-flight mass spectrometry, specifically focusing on taste-related metabolites. During ripening, sucrose content increased. Change in raffinose-family oligosaccharides are reported herein for the first time. The malate and succinate contents increased, while those of citrate, an abundant organic acid, were unchanged. Notably, most amino acids increased, including isoleucine, leucine, and valine, whereas aspartate decreased, and glutamate was unchanged. Furthermore, transcriptomic analysis was performed to analyze the dynamic changes in sugar metabolism, glycolysis, TCA cycle, and amino acid pathways to identify key candidate genes. Taken together, our results elucidate the fundamental taste-related metabolism of durian, which can be exploited to develop durian metabolic and genetic markers in the future.

Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses.

The metabolism of an organism is closely related to both its internal and external environments. Metabolites can act as signal molecules that regulate the functions of genes and proteins, reflecting the status of these environments. This review discusses the metabolism and regulatory functions of O-acetylserine (OAS), S-adenosylmethionine (AdoMet), homocysteine (Hcy), and serine (Ser), which are key metabolites related to sulfur (S)-containing amino acids in plant metabolic networks, in comparison to microbial and animal metabolism. Plants are photosynthetic auxotrophs that have evolved a specific metabolic network different from those in other living organisms. Although amino acids are the building blocks of proteins and common metabolites in all living organisms, their metabolism and regulation in plants have specific features that differ from those in animals and bacteria. In plants, cysteine (Cys), an S-containing amino acid, is synthesized from sulfide and OAS derived from Ser. Methionine (Met), another S-containing amino acid, is also closely related to Ser metabolism because of its thiomethyl moiety. Its S atom is derived from Cys and its methyl group from folates, which are involved in one-carbon metabolism with Ser. One-carbon metabolism is also involved in the biosynthesis of AdoMet, which serves as a methyl donor in the methylation reactions of various biomolecules. Ser is synthesized in three pathways: the phosphorylated pathway found in all organisms and the glycolate and the glycerate pathways, which are specific to plants. Ser metabolism is not only important in Ser supply but also involved in many other functions. Among the metabolites in this network, OAS is known to function as a signal molecule to regulate the expression of OAS gene clusters in response to environmental factors. AdoMet regulates amino acid metabolism at enzymatic and translational levels and regulates gene expression as methyl donor in the DNA and histone methylation or after conversion into bioactive molecules such as polyamine and ethylene. Hcy is involved in Met-AdoMet metabolism and can regulate Ser biosynthesis at an enzymatic level. Ser metabolism is involved in development and stress responses. This review aims to summarize the metabolism and regulatory functions of OAS, AdoMet, Hcy, and Ser and compare the available knowledge for plants with that for animals and bacteria and propose a future perspective on plant research.

Cross-Species Metabolic Profiling of Floral Specialized Metabolism Facilitates Understanding of Evolutional Aspects of Metabolism Among Brassicaceae Species.

Plants produce a variety of floral specialized (secondary) metabolites with roles in several physiological functions, including light-protection, attraction of pollinators, and protection against herbivores. Pigments and volatiles synthesized in the petal have been focused on and characterized as major chemical factors influencing pollination. Recent advances in plant metabolomics have revealed that the major floral specialized metabolites found in land plant species are hydroxycinnamates, phenolamides, and flavonoids albeit these are present in various quantities and encompass diverse chemical structures in different species. Here, we analyzed numerous floral specialized metabolites in 20 different Brassicaceae genotypes encompassing both different species and in the case of crop species different cultivars including self-compatible (SC) and self-incompatible (SI) species by liquid chromatography-mass spectrometry (LC-MS). Of the 228 metabolites detected in flowers among 20 Brassicaceae species, 15 metabolite peaks including one phenylacyl-flavonoids and five phenolamides were detected and annotated as key metabolites to distinguish SC and SI plant species, respectively. Our results provide a family-wide metabolic framework and delineate signatures for compatible and incompatible genotypes thereby providing insight into evolutionary aspects of floral metabolism in Brassicaceae species.

Diversity of Chemical Structures and Biosynthesis of Polyphenols in Nut-Bearing Species.

Nuts, such as peanut, almond, and chestnut, are valuable food crops for humans being important sources of fatty acids, vitamins, minerals, and polyphenols. Polyphenols, such as flavonoids, stilbenoids, and hydroxycinnamates, represent a group of plant-specialized (secondary) metabolites which are characterized as health-beneficial antioxidants within the human diet as well as physiological stress protectants within the plant. In food chemistry research, a multitude of polyphenols contained in culinary nuts have been studied leading to the identification of their chemical properties and bioactivities. Although functional elucidation of the biosynthetic genes of polyphenols in nut species is crucially important for crop improvement in the creation of higher-quality nuts and stress-tolerant cultivars, the chemical diversity of nut polyphenols and the key biosynthetic genes responsible for their production are still largely uncharacterized. However, current technical advances in whole-genome sequencing have facilitated that nut plant species became model plants for omics-based approaches. Here, we review the chemical diversity of seed polyphenols in majorly consumed nut species coupled to insights into their biological activities. Furthermore, we present an example of the annotation of key genes involved in polyphenolic biosynthesis in peanut using comparative genomics as a case study outlining how we are approaching omics-based approaches of the nut plant species.

Differences in impact on adjacent compartments in medial unicompartmental knee arthroplasty versus high tibial osteotomy with identical valgus alignment.

BACKGROUND: It is unclear why medial unicompartmental knee arthroplasty (UKA) with postoperative valgus alignment causes adjacent compartment osteoarthritis more often than high tibial osteotomy (HTO) for moderate medial osteoarthritis of the knee with varus deformity. This study used a computer simulation to evaluate differences in knee conditions between UKA and HTO with identical valgus alignment. METHODS: Dynamic musculoskeletal computer analyses of gait were performed. The hip-knee-ankle angle in fixed-bearing UKA was changed from neutral to 7° valgus by changing the tibial insert thickness. The hip-knee-ankle angle in open-wedge HTO was also changed from neutral to 7° valgus by opening the osteotomy gap. RESULTS: The lateral tibiofemoral contact forces in HTO were larger than those in UKA until moderate valgus alignments. However, the impact of valgus alignment on increasing lateral forces was more pronounced in UKA, which ultimately demonstrated a larger lateral force than HTO. Valgus alignment in UKA caused progressive ligamentous tightness, including that of the anterior cruciate ligament, resulting in compression of the lateral tibiofemoral compartment. Simultaneously, patellofemoral shear forces were slightly increased and excessive external femoral rotation against the tibia occurred due to the flat medial tibial insert surface and decreased lateral compartment congruency. By contrast, only lateral femoral slide against the tibia occurred in excessively valgus-aligned HTO. CONCLUSIONS: In contrast to extra-articular correction in HTO, which results from opening the osteotomy gap, intra-articular valgus correction in UKA with thicker tibial inserts caused progressive ligamentous tightness and kinematic abnormalities, resulting in early osteoarthritis progression into adjacent compartments.

Developmental stage-specific metabolite signatures in Arabidopsis thaliana under optimal and mild nitrogen limitation.

Metabolites influence flowering time, and thus are among the major determinants of yield. Despite the reported role of trehalose 6-phosphate and nitrate signaling on the transition from the vegetative to the reproductive phase, little is known about other metabolites contributing and responding to developmental phase changes. To increase our understanding which metabolic traits change throughout development in Arabidopsis thaliana and to identify metabolic markers for the vegetative and reproductive phases, especially among individual amino acids (AA), we profiled metabolites of plants grown in optimal (ON) and limited nitrogen (N) (LN) conditions, the latter providing a mild but consistent limitation of N. We found that although LN plants adapt their growth to a decreased level of N, their metabolite profiles are strongly distinct from ON plant profiles, with N as the driving factor for the observed differences. We demonstrate that the vegetative and the reproductive phase are not only marked by growth parameters such as biomass and rosette area, but also by specific metabolite signatures including specific single AA. In summary, we identified N-dependent and -independent indicators manifesting developmental stages, indicating that the plant's metabolic status also reports on the developmental phases.

Abnormal knee kinematics caused by mechanical alignment in symmetric bicruciate-retaining total knee arthroplasty are alleviated by kinematic alignment.

BACKGROUND: Bicruciate-retaining total knee arthroplasty (BCR-TKA) was developed to maintain anterior cruciate ligament function and thus reproduce natural knee kinematics postoperatively. Traditional surgical techniques, however, may cause several complications secondary to kinematic conflict and ligament overtension. The objective of this study was to use a computer simulation of symmetric BCR-TKA to evaluate the effects of alternative surgical techniques on knee kinematics and ligaments. METHODS: A musculoskeletal computer model of a healthy knee was constructed and was used to simulate a BCR model with mechanical alignment (MA). Five adjusted models were investigated, characterized, respectively, by kinematic alignment (KA), two degrees increased tibial slope, two-millimeter distal setting of the tibial component, and an undersized femoral component with either MA or KA. RESULTS: All models exhibited a normal femoral position against the tibia at knee extension, with no anterior paradoxical motion during mid-flexion. The healthy knee model showed medial pivot motion and rollback. In contrast, the BCR MA model demonstrated abnormal bi-condylar rollback with excessive tensions of the lateral collateral ligament and posterior cruciate ligament during knee flexion, whereas the undersized femoral model with MA partly reduced both tensions. The BCR KA model retained relatively physiological kinematics and suppressed excessive ligament tensions. However, no adjusted model completely reproduced healthy knee conditions. CONCLUSIONS: The BCR MA model showed abnormal biomechanics due to kinematic conflict between the retained ligaments and the replaced joint surface. Surgeons using symmetric BCR-TKA should consider using the KA method to achieve sufficient ligament laxity throughout knee flexion.

Large medial proximal tibial angles cause excessively medial tibiofemoral contact forces and abnormal knee kinematics following open-wedge high tibial osteotomy.

BACKGROUND: Recurrent varus deformity and poor outcome sometimes occur following open-wedge high tibial osteotomy, but the mechanism remains unclear. The hypothesis of this study was that an excessively large medial proximal tibial angle with lateral joint surface inclination can worsen postoperative knee biomechanics. METHODS: A computer-simulated knee model was validated based on a volunteer knee. Osteotomy models with medial proximal tibial angles ranging from 90° to 97° in 1° increments were developed. Varus alignment correction of the distal femur was performed in each model to maintain identical coronal alignment passing through a point 62.5% lateral to the tibial plateau. The peak tibiofemoral contact forces and knee kinematics were compared in each model during walking and squatting. FINDINGS: All the osteotomy models demonstrated higher peak contact forces on the lateral tibiofemoral joints than on the medial tibiofemoral joints during walking. However, larger medial proximal tibial angles caused excessive increases in medial tibiofemoral contact forces, and the dominant tibiofemoral contact forces shifted to the medial side. Increased medial proximal tibial angles also caused progressive medial collateral ligament tension in knee flexion, but partial medial collateral ligament release effectively reduced medial tibiofemoral contact forces. Models with large medial proximal tibial angles showed nonphysiological roll-forward of the lateral femoral condyle during squatting and no screw-home movement around knee extension. INTERPRETATION: Excessively large medial proximal tibial angles following open-wedge high tibial osteotomy resulted in increased medial tibiofemoral contact forces and abnormal knee kinematics during knee flexion due to medial joint line elevation and ligament imbalance.

Association of foveal avascular zone with the metamorphopsia in epiretinal membrane.

This study was to investigate the relationship between the metamorphopsia and foveal avascular zone (FAZ) parameter in eyes with epiratinal membrane (ERM). We studied patients with an ERM visited retinal service unit at the Kagoshima University Hospital or Shirai Hospital. The best-corrected visual acuity (BCVA), and the degree of metamorphopsia by M -CHARTS™ were evaluated. The 3 × 3 mm optical coherence tomography angiography (OCTA) images of the superficial layer were obtained. Area (mm2), the circularity, eigen value were calculated using ImageJ software. The relationship between visual function, such as best corrected visual acuity (BCVA) and metamorphopsia, and FAZ parameters were studied by Pearson's correlational coefficient. Fifty-four eyes of 51 patients (24 men and 27 women) with an ERM were studied. The mean age of the patients was 69.6 ± 8.20 years. The mean BCVA and metamorphopsia score was 0.31 ± 0.29 logMAR units and 0.49 ± 0.42. There was no significant relationship between BCVA and FAZ parameters. While, metamorphopsia score was significantly and negatively correlated with all of FAZ parameters (area R = - 0.491, P < 0.001; circularity R = - 0.385, P = 0.004; eigenvalue ratio R = - 0.341; P = 0.012). Multiple regression analysis showed the FAZ area was solely and significantly correlated with metamorphopsia score (ß - 0.479, P < 0.001). The size but not the shape of the FAZ was significantly correlated with the degree of metamorphopsia suggesting that it could be an objective parameter of metamorphopsia in ERM patients.