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Abstract Background Somatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy; however, the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration. Methods The chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their in vivo chondrogenic potential was validated through transplantation into a mouse osteochondral defect model. Results All cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse SSCs was observed with supplementation of BMP2 or TGFβ1, whereas chondrogenesis of mouse ASCs and human SSCs was observed with supplementation of BMP2 not TGFβ1. Human ASCs showed no obvious chondrogenesis following single stimulation. Mouse SSCs showed the formation of hyaline-like cartilage which had less fibrous components (COL1/3) with supplementation of TGFβ1. However, human cells developed COL1/3+ tissues with all treatments. Transcriptomic analysis for TGFβ receptors and ligands of cells prior to chondrogenic induction did not indicate their distinct reactivity to the TGFβ1 or BMP2. In the transplanted site in vivo, mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1−/COL3−) but other cell types mainly formed COL1/3-positive fibrous tissues in line with in vitro reactivity to TGFβ1. Conclusion Optimal chondrogenic factors driving chondrogenesis from somatic stem cells are intrinsically distinct among cell types and species. Among them, the response to TGFβ1 may possibly represent the fate of stem cells when locally transplanted into cartilage defects.

The impact of the bone tunnel size relative to body size on clinical results in anterior cruciate ligament (ACL) reconstruction remains unclear. This study aimed to assess the morphological alteration of the tibial tunnel aperture and relationship between the tibial tunnel size relative to the proximal tibia among the tibial tunnel widening (TW) and clinical results following ACL reconstruction. This study comprised 131 patients who had undergone anatomical ACL reconstruction utilizing bone-patellar tendon-bone autografts. The morphology and enlargement of the tibial tunnel were examined via three-dimensional computed tomography 1 week and 1 year postoperatively. The anteroposterior (AP) and mediolateral (ML) positions were determined as a percentage relative to the proximal AP and ML tibial dimensions, respectively. Clinical assessment was conducted 2 years postoperatively. The association between the primary tibial tunnel size among TW and clinical outcomes was examined. The tibial tunnel significantly migrated posterolaterally. The ML diameter significantly widened; however, the AP diameter did not exhibit widening. AP widening was associated with the AP diameter of the primary tibial tunnel ( r  = -0.482, p  < 0.01), and ML widening correlated with the ML diameter of that tunnel ( r  = -0.478, p  < 0.01). However, there was no significant correlation observed between the primary tibial tunnel size and clinical outcomes. The tibial tunnel migrated and enlarged laterally in the ML plane, but did not enlarge in the AP plane. The primary tibial tunnel diameter relative to the proximal tibia negatively correlated with the tibial TW in the AP and ML planes. Level of evidence: level IV., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Previous studies have attempted to determine prognostic factors for predicting the occurrence of noncontact anterior cruciate ligament (ACL) injuries. However, studies on risk factors for noncontact ACL injuries in Asian female soccer players are limited., Purpose: To identify intrinsic risk factors for noncontact ACL injuries among young female Asian soccer players., Study Design: Cohort study; Level of evidence, 2., Methods: This study evaluated 145 female Japanese soccer players for potential risk factors for noncontact ACL injury during the preseason medical assessment. In total, 25 variables were examined-including anthropometric data, joint range of motion, muscle flexibility, muscle strength, and balance measurements. Participants were monitored throughout a single season for noncontact ACL injuries diagnosed by physicians., Results: Noncontact ACL injuries occurred in 13 knees of 13 players (9%). Lower hamstring-to-quadriceps ratio (0.44 ± 0.07 vs 0.50 ± 0.10; P = .04), greater knee extension muscle strength (3.2 ± 0.5 vs 2.7 ± 0.5 N·m/kg; P < .01), and longer playing experience (10.8 ± 3 vs 8.1 ± 4.2 years; P = .02) were significantly associated with new-onset noncontact ACL injuries in young female soccer players. No statistically significant between-group differences were found for any other variables., Conclusion: New-onset noncontact ACL injury in young female soccer players was significantly associated with lower hamstring-to-quadriceps ratio, greater knee extension muscle strength, and longer soccer experience. These findings will help develop strategies for preventing noncontact ACL injuries among female soccer players., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by scholarship donations from the East Japan Railway Company and Shimamura-Syoukai and grants from the Nakatomi Foundation, Japan Sports Medicine Foundation, Japan Sport Council, Japanese Orthopaedic Society for Sports Medicine, Watanabe Memorial Foundation for the Advancement of New Technology, Japan Keirin Autorace Foundation, Japan Society for the Promotion of Science (KAKENHI 20K11358), Japan Orthopaedics Traumatology Foundation, and Japanese Orthopaedic Society of Knee, Arthroscopy and Sports Medicine. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background/objective: This study aimed to clarify the kinematics of bi-cruciate-retaining (BCR) total knee arthroplasty (TKA) by comparing the mechanical alignment (MA) and functional alignment (FA) methods and to evaluate differences between the two alignment methods., Methods: The in vivo kinematics of 20 MA TKA and 20 FA TKA knees were investigated under fluoroscopy during squatting using a two-to three-dimensional registration technique. Accordingly, knee flexion angle, axial rotational angle, varus-valgus angle, anteroposterior translation of the medial and lateral low contact points of the femoral component relative to the tibial component and kinematic pathway were evaluated., Results: No difference in the knee flexion angle was observed between the MA and FA TKA groups. Femoral external rotation was observed in both groups and no significant difference was observed. Significant varus alignment from extension to early flexion range was observed in the FA TKA group. The posterior translation of the medial side was smaller in the FA TKA group than in the MA TKA group. Conversely, no significant difference in the anteroposterior translation of the lateral side was observed. In the kinematic pathway, a medial pivot motion from 0° to 20° of flexion and a lateral pivot motion beyond 20° of flexion were observed in both groups., Conclusion: During squatting in BCR TKA, the FA TKA group significantly showed varus alignment and smaller posterior translation of the medial side than the MA TKA group from extension to early flexion range., Competing Interests: The authors have received grants from 10.13039/100009026Smith & Nephew, 10.13039/100008894Stryker outside this study. No author has a conflict of interest regarding the topics discussed in this study., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Background: This study aimed to evaluate the effects of the differences in initial graft tension (IGT) on patellofemoral alignment in the axial plane after anatomical anterior cruciate ligament reconstruction (ACLR)., Methods: A total of 102 patients who underwent primary anatomical ACLR using a bone-patellar-tendon-bone autograft were enrolled. The grafts were fixed with maximum manual force at full knee extension (higher graft tension; H group) and with 5-20 N at 20° knee flexion which corresponded to 80 N at full knee extension (lower graft tension; L group) pulls in 39 and 63 patients, respectively. All patients underwent computed tomography of the bilateral knee joints with knee extension 1 week postoperatively. The patellofemoral alignment (sulcus angle, lateral trochlear inclination angle, lateral patellofemoral angle (LPFA), condylar-patellar angle (CPA) (lateral facet, patellar tilt), congruence angle, and bisect offset index) on the axial computed tomography images were evaluated, and the side-to-side differences (SSDs) between the injured knee and the contralateral knee were calculated., Results: Congruence angle SSD was remarkably higher in the H group than in the L group (3.8 ± 4.7 vs. 0.4 ± 5.7, P < 0.01). Furthermore, the LPFA SSD and CPA (patellar tilt) SSD were significantly higher in the H group (-1.8 ± 3.1 vs. -0.4 ± 2.7, P = 0.04 and -1.6 ± 2.8 vs. -0.3 ± 2.7, P = 0.04, respectively)., Conclusions: A higher IGT during anatomical ACLR induces a lateral shift and tilt of the patella against the femur immediately after surgery compared with the lower IGT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Archaeosine (G + ) is an archaea-specific tRNA modification synthesized via multiple steps. In the first step, archaeosine tRNA guanine transglucosylase (ArcTGT) exchanges the G15 base in tRNA with 7-cyano-7-deazaguanine (preQ 0 ). In Euryarchaea, preQ 0 15 in tRNA is further modified by archaeosine synthase (ArcS). Thermococcus kodakarensis ArcS catalyzes a lysine-transfer reaction to produce preQ 0 -lysine (preQ 0 -Lys) as an intermediate. The resulting preQ 0 -Lys15 in tRNA is converted to G + 15 by a radical S-adenosyl-L-methionine enzyme for archaeosine formation (RaSEA), which forms a complex with ArcS. Here, we focus on the substrate tRNA recognition mechanism of ArcS. Kinetic parameters of ArcS for lysine and tRNA-preQ 0 were determined using a purified enzyme. RNA fragments containing preQ 0 were prepared from Saccharomyces cerevisiae tRNA Phe -preQ 0 15. ArcS transferred 14 C-labeled lysine to RNA fragments. Furthermore, ArcS transferred lysine to preQ 0 nucleoside and preQ 0 nucleoside 5'-monophosphate. Thus, the L-shaped structure and the sequence of tRNA are not essential for the lysine-transfer reaction by ArcS. However, the presence of D-arm structure accelerates the lysine-transfer reaction. Because ArcTGT from thermophilic archaea recognizes the common D-arm structure, we expected the combination of T. kodakarensis ArcTGT and ArcS and RaSEA complex would result in the formation of preQ 0 -Lys15 in all tRNAs. This hypothesis was confirmed using 46 T. kodakarensis tRNA transcripts and three Haloferax volcanii tRNA transcripts. In addition, ArcTGT did not exchange the preQ 0 -Lys15 in tRNA with guanine or preQ 0 base, showing that formation of tRNA-preQ 0 -Lys by ArcS plays a role in preventing the reverse reaction in G + biosynthesis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A method of synthesizing hydroindole skeletons has been developed by using photocatalytic oxidative dearomatization and an aza-Michael addition sequence. Using this method, optically active hydroindoles, which are often used in natural product synthesis as chiral building blocks, can be easily prepared with >99% ee . Furthermore, the synthesis of melodamide A and (±)-toussaintine C was achieved using this method as a key step.

All kinds of RNA molecules can be produced by in vitro transcription using T7 RNA polymerase using DNA templates obtained by solid-phase chemical synthesis, primer extension, PCR, or DNA cloning. The oligonucleotide design, however, is a challenge to nonexperts as this relies on a set of rules that have been established empirically over time. Here, we describe a Python program to facilitate the rational design of oligonucleotides, calculated with kinetic parameters for enhanced in vitro transcription (ROCKET). The Python tool uses thermodynamic parameters, performs folding-energy calculations, and selects oligonucleotides suitable for the polymerase extension reaction. These oligonucleotides improve yields of template DNA. With the oligonucleotides selected by the program, the tRNA transcripts can be prepared by a one-pot reaction of the DNA polymerase extension reaction and the transcription reaction. Also, the ROCKET-selected oligonucleotides provide greater transcription yields than that from oligonucleotides selected by Primerize, a leading software for designing oligonucleotides for in vitro transcription, due to the enhancement of template DNA synthesis. Apart from over 50 tRNA genes tested, an in vitro transcribed self-cleaving ribozyme was found to have catalytic activity. In addition, the program can be applied to the synthesis of mRNA, demonstrating the wide applicability of the ROCKET software., (© 2024 Matsuda et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Purpose: The tibial anatomical anteroposterior (AP) axis "Akagi's line" was originally defined on computed tomography (CT) in total knee arthroplasty (TKA); however, its intraoperative reproducibility remains unknown. This study aimed to evaluate the intraoperative reproducibility of the Akagi's line and its effect on postoperative clinical outcomes., Methods: This prospective study included 171 TKAs. The rotational angle of the intraoperative Akagi's line relative to the original Akagi's line (RAA) defined on CT was measured. The RAA was calculated based on the tibial component rotational angles relative to the intraoperative Akagi's line measured using the navigation system and CT. The effects of RAA on postoperative clinical outcomes and rotational alignments of components were also evaluated., Results: The mean absolute RAA (standard deviation) value was 5.5° (3.9°). The range of RAA was 22° internal rotation to 16° external rotation. Intraoperative Akagi's line outliers (RAA > 10°) were observed in 14% of the knees (24 knees). In outlier analysis, the tibial component rotation angle was externally rotated 6.5° (5.6°) in the outlier group and externally rotated 3.7° (4.2°) in the nonoutlier group (≤10°), with a significant difference between the two groups. Additionally, the outlier group (RAA > 10°) showed lower postoperative clinical outcomes., Conclusion: The original Akagi's line defined on CT showed insufficient reproducibility intraoperatively. The poor intraoperative detection of Akagi's line could be the reason for the tibial component rotational error and worse postoperative clinical outcomes., Level of Evidence: Level IV, case series., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Previous studies have attempted to determine if certain risk factors can predict the occurrence of a lateral ankle sprain (LAS) in female soccer players. Unfortunately, there is limited evidence with regard to risk factors associated with an LAS in female soccer players., Purpose: To identify intrinsic risk factors for an LAS among young female soccer players., Study Design: Cohort study; Level of evidence, 2., Methods: Participants were 161 young female soccer players in Japan who were evaluated for LAS risk factors during a preseason medical assessment. The assessment included anthropometric, joint laxity, joint range of motion, muscle flexibility, muscle strength, and balance measurements. Each athlete's history of LASs was also collected. The participants were monitored during a single-yearseason for LASs, as diagnosed by physicians., Results: There were 26 instances of an LAS in 25 players (15.5%) during the season. Injured players were significantly more likely to have sustained a previous ankle sprain ( P = .045) and demonstrated significantly worse balance than their peers without an LAS during the double- and single-leg balance tests ( P = .008 for both). Athletes with lower hamstring-to-quadriceps muscle strength ratios were also significantly more likely to sustain an LAS ( P = .02)., Conclusion: Poor balance, a low hamstring-to-quadriceps ratio, and a history of ankle sprains were associated with an increased risk of LASs in young female soccer players in the current study. These findings may be useful for developing a program to prevent LASs in this population., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Scholarship donations were received from East Japan Railway Company and Shimamura-Syoukai. Grants were received from the Nakatomi Foundation, Japan Sports Medicine Foundation, Japan Sport Council, Japanese Orthopaedic Society for Sports Medicine, Watanabe Memorial Foundation for the Advancement of New Technology, Japan Keirin Autorace Foundation, Japan Society for the Promotion of Science (KAKENHI 20K11358), Japan Orthopaedics Traumatology Foundation, and Japanese Orthopaedic Society of Knee, Arthroscopy and Sports Medicine. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

TrmH is a eubacterial tRNA methyltransferase responsible for formation of 2'-O-methylguaosine at position 18 (Gm18) in tRNA. In Escherichia coli cells, only 14 tRNA species possess the Gm18 modification. To investigate the substrate tRNA selection mechanism of E. coli TrmH, we performed biochemical and structural studies. Escherichia coli TrmH requires a high concentration of substrate tRNA for efficient methylation. Experiments using native tRNA SerCGA purified from a trmH gene disruptant strain showed that modified nucleosides do not affect the methylation. A gel mobility-shift assay reveals that TrmH captures tRNAs without distinguishing between relatively good and very poor substrates. Methylation assays using wild-type and mutant tRNA transcripts revealed that the location of G18 in the D-loop is very important for efficient methylation by E. coli TrmH. In the case of tRNASer, tRNATyrand tRNALeu, the D-loop structure formed by interaction with the long variable region is important. For tRNAGln, the short distance between G18 and A14 is important. Thus, our biochemical study explains all Gm18 modification patterns in E. coli tRNAs. The crystal structure of E. coli TrmH has also been solved, and the tRNA binding mode of E. coli TrmH is discussed based on the structure., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society.)

Background: Previous studies have aimed to determine the use of certain risk factors in predicting the occurrence of noncontact anterior cruciate ligament (ACL) injuries. Unfortunately, evidence regarding noncontact ACL injuries in male American football players is limited. This prospective cohort study aimed to identify intrinsic risk factors for noncontact ACL injury among male American football players., Methods: This study evaluated 152 male American football players in Japan for potential noncontact ACL injury risk factors during a preseason medical assessment, including anthropometric, joint laxity, and flexibility, muscle flexibility, muscle strength, and balance measurements. A total of 25 variables were examined. Participants were monitored during each season for noncontact ACL injury, as diagnosed by physicians., Results: Noncontact ACL injuries occurred in 11 knees of 11 players (prevalence; 7.1 %). Injured players were significantly more likely to have lightweight ( P  = 0.049). No statistically significant between-group differences were found for any other variables. Participants with a lower hamstring to quadriceps (H/Q) ratio ( P  = 0.04) were more likely to sustain noncontact ACL injuries., Conclusion: Lower H/Q ratio and lower body weight were significantly associated with new-onset noncontact ACL injury in male American football players. These findings will help develop strategies to prevent noncontact ACL injuries in male American football players., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Background: Bicruciate-retaining (BCR) prosthesis has been introduced to recreate normal knee movement by preserving both the anterior and posterior cruciate ligaments. However, the use of BCR total knee arthroplasty (TKA) is still debatable because of several disappointing reports. We have been performing BCR TKAs with personalized alignment (PA). This study aimed to reveal the limb alignment and soft tissue balance of FA-BCR TKAs and compare the clinical outcomes of FA-BCR TKAs with those of unicompartmental knee arthroplasty (UKA)., Methods: Fifty BCR TKAs and 58 UKAs were included in this study. The joint component gaps of BCR TKA were evaluated intraoperatively and the postoperative hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were measured using full-length standing radiography. The short-term clinical outcomes of BCR TKAs were compared with those of UKA using the scoring system of 2011 Knee Society Scoring (KSS) and the knee injury and osteoarthritis outcome score (KOOS) at an average of 2 years postoperatively (1-4yeras)., Results: The coronal alignment values of PA-BCR TKA were as follows: HKA angle, 177.9° ± 2.3°; MPTA, 85.4° ± 1.9°; and LDFA, 87.5° ± 1.9°. The joint component gaps at flexion angles of 10°, 30°, 60°, and 90° were 11.1 ± 1.2, 10.9 ± 1.4, 10.7 ± 1.3, and 11.2 ± 1.4 mm for the medial compartment and 12.9 ± 1.5, 12.6 ± 1.8, 12.5 ± 1.8 and 12.5 ± 1.7 mm for the lateral compartment, respectively. The patient expectation score and maximum extension angle of PA-BCR TKA were significantly better than those of UKAs., Conclusions: The short-term clinical outcomes of PA-BCR TKA were comparable or a slightly superior to those of UKAs., (© 2023. The Author(s).)

Purpose: Patellofemoral (PF) compartment cartilage lesions are a frequent problem after anterior cruciate ligament (ACL) reconstruction. This study aimed to determine the factors that influence PF cartilage lesions after anatomical ACL reconstruction., Methods: This study enrolled a total of 114 patients who did not manifest PF compartment cartilage lesions during anatomical ACL reconstruction and underwent second-look arthroscopy 18 months postoperatively. Arthroscopy using the International Cartilage Repair Society (ICRS) classification was used to assess cartilage lesions. The correlation between surgical findings, radiographic factors, and clinical factors and change of ICRS grade was analysed. Multivariate regression analysis was conducted to reveal the independent risk factors for PF cartilage lesions among patients' demographic data and parameters that correlated with the change of ICRS grade in the correlation analyses., Results: ICRS grade changes in PF cartilage were significantly correlated with age, sex, quadriceps strength at 1 year postoperatively, hamstrings strength at pre- and 1 year postoperatively, and single leg hop test at 1 year postoperatively. However, no significant correlation was found between the time between injury and surgery, posterior tibial slope angle, pre- and postoperative Tegner activity scale, graft type, initial graft tension, meniscus injury, meniscus injury treatment, pre- and postoperative range of motion, anteroposterior laxity and preoperative quadriceps strength, and the change in ICRS grade. Multivariate regression analysis revealed male (P = 0.019) and quadriceps strength weakness at 1 year postoperatively (P = 0.009) as independent risk factors for PF cartilage lesions., Conclusions: Quadriceps strength weakness 1 year after ACL reconstruction and males were correlated with a new PF cartilage lesion after anatomical ACL reconstruction, with no significant correlation between bone-patellar tendon-bone autograft, initial graft tension, or extension deficit and new PF cartilage lesion. Rehabilitation that focuses on quadriceps strength after ACL reconstruction is recommended to prevent new PF cartilage lesions., Level of Evidence: Level IV., (© 2023. The Author(s).)

Background: Difference in the finite helical axis of the knee joints before and after anterior cruciate ligament-preserving knee arthroplasties such as unicompartmental knee arthroplasty and bi-cruciate-retaining total knee arthroplasty remains unknown. This study compared the knee finite helical axes before and after bi-cruciate-preserving knee arthroplasty., Methods: Patients undergoing medial unicompartmental knee arthroplasty and bi-cruciate-retaining total knee arthroplasty were included. Under fluoroscopy, participants performed a deep knee bend before and after surgery. A two/three-dimensional registration technique was employed to measure tibiofemoral kinematics. Femoral finite helical axis was calculated in a flexion range of 0-120° using 30° windows (early-, mid-, late-, and deep-flexion phases)., Findings: In unicompartmental knee arthroplasty, the preoperative knee vertical angle was larger than the postoperative vertical angle in mid- and deep-flexion phases. The postoperative knee vertical angle was smaller in unicompartmental knee arthroplasty than in bi-cruciate-retaining total knee arthroplasty. In unicompartmental knee arthroplasty, the preoperative horizontal angle was smaller than the postoperative horizontal angle in the early-flexion phase. However, in bi-cruciate-retaining total knee arthroplasty, the preoperative horizontal angle was larger than the postoperative horizontal angle in mid- and deep-flexion phases. The horizontal angle was smaller before unicompartmental knee arthroplasty than that before bi-cruciate-retaining total knee arthroplasty in early-, mid-, and deep-flexion phases. However, the vertical angle was larger after unicompartmental knee arthroplasty than that after bi-cruciate-retaining total knee arthroplasty in the early-flexion phase., Interpretation: The knee finite helical axes before and after unicompartmental knee arthroplasty differed from those before and after bi-cruciate-retaining total knee arthroplasty., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Compartmentalization of RNA in biopolymer-rich membraneless organelles is now understood to be pervasive and critical for the function of extant biology and has been proposed as a prebiotically plausible way to accumulate RNA. However, compartment-RNA interactions that drive encapsulation have the potential to influence RNA structure and function in compartment- and RNA sequence-dependent ways. Here, we detail next-generation sequencing (NGS) experiments performed in membraneless compartments called complex coacervates to characterize the fold of many different transfer RNAs (tRNAs) simultaneously under the potentially denaturing conditions of these compartments. Notably, we find that natural modifications favor the native fold of tRNAs in these compartments. This suggests that covalent RNA modifications could have played a critical role in metabolic processes at the origin of life.

Although an anterior cruciate ligament (ACL) deficiency induces knee osteoarthritis, particularly in the medial compartment, the kinematics remains partially unclear. This study investigated the in vivo knee kinematics of ACL-deficient and normal knees by comparing them during squatting. This prospective comparative study included 17 ACL-deficient knees and 20 normal knees. The kinematics was investigated under fluoroscopy using a two- to three-dimensional registration technique. The anteroposterior (AP) translation of the medial and lateral sides of the femur, axial rotation of the femur relative to the tibia, and kinematic pathways were evaluated and compared. At first, the medial AP position of the femur translated anteriorly from 0° to midflexion, afterward it translated posteriorly in both ACL-deficient and normal knees. However, the medial AP position of the femur in the ACL-deficient knees was located significantly posteriorly compared with normal knees at 0-110° flexion. The lateral AP position of the femur translated posteriorly from 0° to 150° flexion in both ACL-deficient and normal knees. The lateral AP position of the femur in the ACL-deficient knees was located significantly posteriorly compared with that in normal knees at 0-10° flexion. The femur showed external rotation from 0° to 150° flexion in both ACL-deficient and normal knees. A medial pivot motion and subsequent bicondylar rollback were observed in both knees in the kinematic pathway. In conclusion, the AP position of the femur relative to the tibia was altered due to ACL deficiency, particularly in the medial compartment., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Bi-cruciate stabilized (BCS) total knee arthroplasty (TKA) was developed to approximate normal knee kinematics and is expected to improve clinical outcomes. However, the effects of soft tissue balance at the medial or lateral compartment on patient-reported outcome measures (PROMs) following BCS TKA are unclear. The purpose of this study was to clarify the relationship between the medial or lateral component gaps and PROMs following BCS TKA. One hundred seventeen knees with varus deformities which underwent BCS TKA were included in this study. They were divided into two groups according to the validated Japanese version of the Knee Injury and Osteoarthritis Outcome Score for each subscale of pain, symptoms, and activities of daily living (ADL) at 1 year postoperatively: group H consisted of patients with ≥90 points and group L consisted of patients with <90 points. Intraoperative medial and lateral joint laxities at 0°, 30°, 60°, 90°, and 120° flexion measured using a tensor device were compared between the two groups in each subscale. In the pain subscale, the medial joint laxities at 30° ( p  < 0.05) and 60° flexion ( p  < 0.05) in group H were significantly smaller than those in group L. In the ADL subscale, the medial joint laxity at 60° flexion in group H was significantly smaller than that in group L ( p  < 0.05). In the symptom subscale, the lateral joint laxity at 60° flexion in group H was significantly smaller than that in group L ( p  < 0.05). Surgeons should pay attention to the importance of both medial and lateral joint stabilities to achieve better postoperative PROMs following BCS TKA., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Given the frequency of hamstring strain injuries (HSI) among male college American football players, several studies have attempted to determine whether certain risk factors can predict their occurrence. However, no consensus on modifiable risk factors for HSIs in male college American football players has yet been reached to prevent these injuries. This study aimed to clarify risk factors for HSI prospectively in college male American football players., Methods: A total of 78 male college American football players, whose positions were limited to skill positions, were medically assessed for potential risk factors of HSI. The preseason medical assessment included anthropometric measurements, joint laxity and flexibility, muscle flexibility, muscle strength, and balance ability., Results: HSI occurred in a total of 25 thighs from 25 players (32.1%). Injured players had significantly lower hamstring flexibility (p = 0.02) and hamstring to quadriceps strength ratio (H/Q) (p = 0.047) compared to uninjured players. Additionally, injured players had significantly lower general joint laxity scores, especially for the total (p = 0.04), hip (p = 0.007), and elbow (p = 0.04) scores, compared to uninjured players., Conclusions: Lower hamstring flexibility, lower hamstring to quadriceps strength ratio, and lower general joint laxity score were identified as risk factors for HSI in male college American football players placed in skill positions. The muscle flexibility and H/Q ratio could be useful in preventing HSI in such players., (© 2023. The Author(s).)

4-Thiouridine (s 4 U) is a modified nucleoside, found at positions 8 and 9 in tRNA from eubacteria and archaea. Studies of the biosynthetic pathway and physiological role of s 4 U in tRNA are ongoing in the tRNA modification field. s 4 U has also recently been utilized as a biotechnological tool for analysis of RNAs. Therefore, a selective and sensitive system for the detection of s 4 U is essential for progress in the fields of RNA technologies and tRNA modification. Here, we report the use of biotin-coupled 2-aminoethyl-methanethiosulfonate (MTSEA biotin-XX) for labeling of s 4 U and demonstrate that the system is sensitive and quantitative. This technique can be used without denaturation; however, addition of a denaturation step improves the limit of detection. Thermus thermophilus tRNAs, which abundantly contain 5-methyl-2-thiouridine, were tested to investigate the selectivity of the MTSEA biotin-XX s 4 U detection system. The system did not react with 5-methyl-2-thiouridine in tRNAs from a T. thermophilus tRNA 4-thiouridine synthetase ( thiI ) gene deletion strain. Thus, the most useful advantage of the MTSEA biotin-XX s 4 U detection system is that MTSEA biotin-XX reacts only with s 4 U and not with other sulfur-containing modified nucleosides such as s 2 U derivatives in tRNAs. Furthermore, the MTSEA biotin-XX s 4 U detection system can analyze multiple samples in a short time span. The MTSEA biotin-XX s 4 U detection system can also be used for the analysis of s 4 U formation in tRNA. Finally, we demonstrate that the MTSEA biotin-XX system can be used to visualize newly transcribed tRNAs in S. cerevisiae cells., (© 2023 Sugio et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Background: Medial-pivot type total knee arthroplasty is designed to reproduce physiological femoral rotational kinematics during knee flexion; however, its rotational kinematics in valgus knees remain unknown. This study's hypothesis is that its kinematics show the similar medial pivot motion in valgus knees as in varus knees., Methods: This retrospective study included 50 cases of primary medial-pivot type total knee arthroplasty performed with navigation for knee osteoarthritis. Cases were grouped as valgus (n = 20) or varus (n = 30). In valgus knees, surgeons used preoperative manual testing to confirm that alignment was correctable. They evaluated femoral rotational kinematics at maximum extension, 30°, 60°, 90°, and maximum flexion, using a navigation system, both before and after implantation. Finally, intraoperative rotational kinematics, postoperative patient-reported outcomes, and knee range of motion were compared between the two groups., Findings: Before implantation, both valgus and varus knees displayed external femoral rotation relative to the tibia during knee flexion. The rotation magnitude was significantly larger in varus knees at 60°, 90°, and maximum flexion angles compared to valgus knees (P < 0.05). In contrast, after implantation, both groups displayed external femoral rotation of 12-13° during knee flexion with no significant differences between the two groups at any knee flexion angle tested (P > 0.05). Short-term clinical outcomes were comparable between valgus and varus knees., Interpretation: Postoperatively, medial-pivot type total knee arthroplasty for knee osteoarthritis resulted in external femoral rotation during knee flexion. Notably, this occurred even in valgus knees with good short-term clinical outcomes., Competing Interests: Declaration of Competing Interest Our institute has received donations for research from Medacta Japan KK and Stryker Japan KK. They had no role in the study design, data collection, analysis, or interpretation, or manuscript preparation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Transfer RNAs undergo diverse posttranscriptional modifications to regulate a myriad of cellular events including translation, stress response, and viral replication. These posttranscriptional modifications are synthesized by site-specific modification enzymes. Recent RNA-seq techniques have revealed multiple features of tRNA such as tRNA abundance, tRNA modification, and tRNA structure. Here, we adapt a tRNA-sequencing technique and design a new functional analysis where we perform mutational profiling of tRNA modifications to gain mechanistic insights into how tRNA modification enzymes recognize substrate tRNA. Profiling of Geobacillus stearothermophilus tRNAs and protein orthology analysis predict the existence of natural modifications in 44 tRNA molecular species of G. stearothermophilus. We selected the 1-methyladenosine modification at position 22 (m 1 A22) and tRNA (m 1 A22) methyltransferase (TrmK) for further analysis. Relative quantification of m 1 A22 levels in 59 tRNA transcripts by mutational profiling reveals that TrmK selectively methylates a subset of tRNAs. Using 240 variants of tRNA Leu transcripts, we demonstrate the conserved nucleosides including U8, A14, G15, G18, G19, U55, Purine57, and A58 are important for the methyl transfer reaction of TrmK. Additional biochemical experiments reveal that TrmK strictly recognizes U8, A14, G18, and U55 in tRNA. Furthermore, these findings from tRNA Leu variants were crossvalidated using variants of three different tRNA species. Finally, a model of the TrmK-tRNA complex structure was constructed based on our findings and previous biochemical and structural studies by others. Collectively, our study expands functional analyses of tRNA modification enzyme in a high-throughput manner where our assay rapidly identifies substrates from a large pool of tRNAs., Competing Interests: Conflict of interest The authors declare no conflict of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Transfer RNA (tRNA) delivers amino acids to the ribosome and functions as an essential adapter molecule for decoding codons on the messenger RNA (mRNA) during protein synthesis. Before attaining their proper activity, tRNAs undergo multiple post-transcriptional modifications with highly diversified roles such as stabilization of the tRNA structure, recognition of aminoacyl tRNA synthetases, precise codon-anticodon recognition, support of viral replication and onset of immune responses. The synthesis of the majority of modified nucleosides is catalyzed by a site-specific tRNA modification enzyme. This chapter provides a detailed protocol for using mutational profiling to analyze the enzymatic function of a tRNA methyltransferase in a high-throughput manner. In a previous study, we took tRNA m 1 A22 methyltransferase TrmK from Geobacillus stearothermophilus as a model tRNA methyltransferase and applied this protocol to gain mechanistic insights into how TrmK recognizes the substrate tRNAs. In theory, this protocol can be used unaltered for studying enzymes that catalyze modifications at the Watson-Crick face such as 1-methyladenosine (m 1 A), 3-methylcytosine (m 3 C), 3-methyluridine (m 3 U), 1-methylguanosine (m 1 G), and N2,N2-dimethylguanosine (m 2 2 G)., (Copyright © 2023. Published by Elsevier Inc.)

There is a multitude of small (<100nt) RNAs that serve diverse functional roles in biology. Key amongst these is transfer RNA (tRNA), which is among the most ancient RNAs and is part of the translational apparatus in every domain of life. Transfer RNAs are also the most heavily modified class of RNAs. They are essential and their misregulation, due to mutated sequences or loss of modification, can lead to disease. Because of the severe phenotypes associated with mitochondrial tRNA defects in particular, the desire to deliver repaired tRNAs via droplets such as lipid nanoparticles or other compartments is an active area of research. Here we describe how to use our tRNA Structure-seq method to study tRNAs and other small RNAs in two different biologically relevant contexts, peptide-rich droplets and in vivo., (Copyright © 2023. Published by Elsevier Inc.)

Background: Tunnel widening (TW) after anterior cruciate ligament (ACL) reconstruction has been a research area of interest in ACL reconstruction. In recent years, it has been noted that posterior tibial slope (PTS) affects several types of outcomes after ACL reconstruction including TW. However, the relationships between femoral and tibial TW and between PTS and TW following anatomical ACL reconstruction using a bone-patellar tendon-bone (BTB) graft are often not understood. Therefore, the purpose of this study was to retrospectively clarify the magnitude of femoral and tibial TW and the effect of PTS on TW following anatomical ACL reconstruction using a BTB graft., Methods: A total of 111 patients who underwent isolated ACL reconstructions using BTB grafts were included in this study. Femoral and tibial tunnel aperture areas were measured using three-dimensional computed tomography (3D CT) at 1 week and 1 year postoperatively, and femoral and tibial TW (%) was calculated. Lateral and medial PTS was also measured using 3D CT., Results: As compared with 1 week postoperatively, the mean tibial tunnel aperture areas increased by 30.6% ± 28.5%, and the mean femoral tunnel aperture areas increased by 28.3% ± 27.9% when measured at 1 year postoperatively. Although no significant difference was observed between femoral and tibial TW, a significant positive correlation was noted between femoral and tibial TW (r = 0.240, p = 0.011). A significant correlation was observed only between lateral PTS and tibial TW (r = 0.354, p < 0.001). There was no significant correlation between medial PTS and tibial TW, lateral PTS and femoral TW, or medial PTS and femoral TW., Conclusion: Significant positive correlation was observed between femoral and tibial TW. Steeper lateral PTS correlated with greater tibial TW; on the other hand, medial PTS did not correlate with tibial TW. Although lateral PTS affected tibial TW, it did not affect femoral TW., Competing Interests: Our institutions have received grants from Smith & Nephew outside this work., (© 2022 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Background: This study aimed to determine the kinematics of medial pivot total knee arthroplasty by comparing weight-bearing and non-weight-bearing deep knee bending and to evaluate the effect of the weight-bearing state on the kinematics., Methods: The kinematics of 19 knees were investigated under fluoroscopy during squatting (weight-bearing) and active-assisted knee bending (non-weight-bearing) using two- to three-dimensional registration technique. Accordingly, range of motion, anteroposterior translation for the medial and lateral low contact points, axial rotation of the femoral component relative to the tibial component and kinematic pathway were evaluated., Findings: There was no difference in range of motion between the two states. The medial anteroposterior translation showed no significant movement with no anterior translation in both the weight-bearing and non-weight-bearing from 0° to 90° of flexion. Regarding the lateral anteroposterior translation, a posterior translation was observed during weight-bearing, whereas a slight anterior translation from 0° to 30° of flexion and subsequent posterior translation were found in the non-weight-bearing. Femoral external rotation was observed in the weight-bearing, whereas femoral internal rotation was seen from 0° to 30° of flexion and subsequent femoral external rotation was observed in the non-weight-bearing. The kinematic pathway showed medial pivot motion and subsequent bicondylar rollback in the weight-bearing, whereas only medial pivot motion was observed in the non-weight-bearing., Interpretation: The medial anteroposterior translation of the femur during deep knee bending showed no anterior motion in the two states. The lateral anteroposterior translation and femoral rotation were different in the mid-flexion range between the two states., Competing Interests: Declaration of Competing Interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bicruciate-stabilized total knee arthroplasty (BCS TKA) has been developed to improve TKA kinematic performance. However, the relationship between in vivo kinematics and patient-reported outcomes (PROs) has not been well described. This study was performed to clarify the relationship between in vivo kinematics and PROs in a cohort of patients undergoing BCS TKA. Forty knees were evaluated using a two-dimensional to three-dimensional registration technique obtained from sagittal plane fluoroscopy. In vivo kinematics including anteroposterior (AP) translation and tibiofemoral rotation were evaluated. Knee Society scores (KSSs) and Knee injury and Osteoarthritis Outcome Scores (KOOSs) were assessed before and after surgery. Relationships between tibiofemoral kinematics assessed with the knee in different positions of knee flexion and PROs were evaluated using Spearman's correlation analysis. The study demonstrated a significant negative correlation ( r  =  - 0.33) between medial AP translation from minimum flexion to 30 degrees flexion and postoperative KOOS activities of daily living subscale. A significant positive correlation ( r  = 0.51) was found between the femoral external rotation from minimum flexion to 30 degrees flexion and improvement of the KOOS pain subscale. No correlation was found between the lateral AP translation and PROs. Achieving medial AP and femoral external rotation stability in early flexion may be important in optimizing postoperative PROs., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Soft tissue balance is important for a good clinical result in total knee arthroplasty. Nevertheless, the appropriate evaluation of the intraoperative gap has not been established. We investigated the relationship between physical characteristics and gap differences due to distraction force, in order to determine whether intraoperative adjustment of the distraction force can be considered based on the physical characteristics of the patient., Methods: A total of 115 varus knees in which primary total knee arthroplasty was performed were retrospectively evaluated. The component gaps were measured under 60 and 80 N. The gap difference under 60 and 80 N was calculated. We performed a linear regression analysis to determine the correlation between the gap differences and patient parameters., Findings: Each gap was significantly larger under 80 N than under 60 N. The component gap difference is larger in the lateral compartment than in the medial compartment at each knee flexion angle. The gap difference negatively correlated with preoperative hip-knee-ankle angle at a knee flexion of 0° and 120° (r = -0.21, -0.19; p = 0.02, 0.05) and positively correlated with BMI in the lateral compartment at a knee flexion of 90° (r = 0.31, p < 0.001)., Interpretation: The difference in the intraoperative gap due to the joint distraction force was affected by the preoperative HKA axis angle and the body mass index in the lateral compartment. Surgeons should consider the effect of preoperative limb alignment and body mass index in interpreting intraoperative gap measurement., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to elucidate the effects of the difference of initial graft tension on the femorotibial relationship on an axial plane and its chronological change following anatomical anterior cruciate ligament (ACL) reconstruction., Methods: A total of 63 patients who underwent anatomical ACL reconstruction were included in this study. The graft was fixed at full knee extension with manual maximum (higher graft tension; group H) and 80 N (lower graft tension; group L) pulls in 31 and 32 patients, respectively. The femorotibial positional relationship in axial computed tomography at 1 week and 1 year postoperatively were retrospectively evaluated. The side-to-side differences (SSDs) and the amount of changes of SSDs over 1 year were compared between groups., Results: The SSDs of the external rotational angle of the tibia in group H were significantly larger than those in group L at postoperative 1 week (2.7 ± 3.9° vs. 0.3 ± 3.3°; P < 0.01). The amount of internal rotational changes of SSDs of the internal-external rotational angles over 1 year in group H was significantly larger than that in group L (-3.6 ± 3.9° vs. - 0.3 ± 2.7°; P < 0.01). No significant differences were observed on the anterior-posterior translation distance and medial-lateral shift distance., Conclusion: The application of higher initial graft tension resulted in excessive external rotation of the tibia to the femur at 1 week postoperatively in anatomical ACL reconstruction, and the excessive early external tibial rotation had resolved over 1 year., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Chronic ankle instability (CAI) is commonly encountered in soccer players. The feelings of instability and anxiety caused by CAI can lead to poor performance, such as difficulty in sharp change of direction during soccer play. The single-leg drop landing (SLDL) task is often used to evaluate dynamic postural stability., Purpose/hypothesis: The purpose of this study was to clarify whether dynamic stability measured during SLDL is altered in male collegiate soccer players with CAI. The hypothesis was that athletes with CAI would show poor dynamic postural stability., Study Design: Controlled laboratory study., Methods: A total of 103 male collegiate soccer players were recruited, and their limbs were classified based on the new international CAI criteria. All players performed three 5-second SLDL trials on a force plate. The main outcome measures included time to stabilization of the horizontal ground-reaction force (GRF); peak GRF in the vertical, horizontal, and sagittal directions; and trajectory length of the center of pressure during SLDL., Results: Data from 59 CAI limbs and 147 non-CAI limbs were collected in this study. Time to stabilization of horizontal GRF was significantly longer in the CAI limbs ( P < .001), and the peak GRFs in all directions were significantly lower in the CAI limbs (vertical, P < .001; horizontal, P < .001; sagittal, P = .001). Additionally, the trajectory length of the center of pressure was significantly greater in the CAI limbs ( P = .004)., Conclusion: Soccer players with CAI had decreased dynamic postural stability that led them to land softly when performing the SLDL task. Measurement of dynamic postural stability may be useful in the evaluation of CAI., Clinical Relevance: Our findings may be useful for strategies of daily training or as an evaluation tool., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Funding was provided in the form of scholarships from the East Japan Railway Company and Shimamura-Syoukai, as well as grants from the Nakatomi Foundation; the Japanese Orthopaedic Society of Knee, Arthroscopy and Sports Medicine; the Japanese Sports Medicine Foundation; the Japan Sport Council; the Watanabe Memorial Foundation for the Advancement of Technology; and the Japan Orthopaedics Traumatology Foundation. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Purpose: The purpose of this study was to clarify the effects of applying different amounts of initial graft tension on the femorotibial positional relationship on the axial plane after anatomical ACL reconstruction., Methods: Eighty patients who underwent isolated ACL reconstructions using bone-patellar tendon-bone grafts were included in this study. In 40 of the 80 patients, the grafts were fixed at full knee extension with maximum manual force (high graft tension; Group H), whereas in the other 40 patients, the grafts were fixed at full knee extension with force of 80 N (low graft tension; Group L). One week postoperatively, all patients underwent computed tomography (CT) on bilateral knee joints with knee extension. The femorotibial positional relationship in axial CT images were retrospectively evaluated. Side-to-side differences (the surgical side minus the unaffected side) were calculated in these variables., Results: The side-to-side differences in anterior tibial translation distances were - 1.8 ± 2.1 mm in Group H and - 1.9 ± 2.0 mm in Group L, with no significant difference between the two groups. The side-to-side differences in tibial lateral shifts were - 0.2 ± 1.5 mm in Group H and 0.0 ± 1.4 mm in Group L, with no significant difference between the two groups. The side-to-side differences in tibial external rotation angles were 2.7 ± 4.5° in Group H and 0.3 ± 3.3° in Group L, with a significant difference between the two groups (P < 0.01)., Conclusion: Applying high initial graft tension (maximum manual force) resulted in the external rotation of the tibia against the femur just after anatomical ACL reconstruction. In contrast, applying low initial graft tension (80 N at full knee extension) did not change the femorotibial rotational relationship., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

RNA structure plays roles in myriad cellular events including transcription, translation, and RNA processing. Genome-wide analyses of RNA secondary structure in vivo by chemical probing have revealed critical structural features of mRNAs and long ncRNAs. Here, we examine the in vivo secondary structure of a small RNA class, tRNAs. Study of tRNA structure is challenging because tRNAs are heavily modified and strongly structured. We introduce "tRNA structure-seq," a new workflow that accurately determines in vivo secondary structures of tRNA. The workflow combines dimethyl sulfate (DMS) probing, ultra-processive RT, and mutational profiling (MaP), which provides mutations opposite DMS and natural modifications thereby allowing multiple modifications to be identified in a single read. We applied tRNA structure-seq to E. coli under control and stress conditions. A leading folding algorithm predicts E. coli tRNA structures with only ∼80% average accuracy from sequence alone. Strikingly, tRNA structure-seq, by providing experimental restraints, improves structure prediction under in vivo conditions to ∼95% accuracy, with more than 14 tRNAs predicted completely correctly. tRNA structure-seq also quantifies the relative levels of tRNAs and their natural modifications at single nucleotide resolution, as validated by LC-MS/MS. Our application of tRNA structure-seq yields insights into tRNA structure in living cells, revealing that it is not immutable but has dynamics, with partial unfolding of secondary and tertiary tRNA structure under heat stress that is correlated with a loss of tRNA abundance. This method is applicable to other small RNAs, including those with natural modifications and highly structured regions.

Background: A tibial cut with the native posterior tibial slope (PTS) is a theoretical prerequisite in bicruciate-retaining total knee arthroplasty (BCRTKA) to regain physiological knee kinematics. The present study reveals tibial morphological risk factors of trauma to the posteromedial structures of the knee during tibial bone resection in BCRTKA., Methods: Fifty patients undergoing BCRTKA for varus knee osteoarthritis were analyzed. A three-dimensional tibial bone model was reconstructed using a computed tomography-based preoperative planning system, and the coronal tibial slope (CTS) and medial PTS (MPTS) were measured. Then, we set the simulated tibial cutting plane neutral on the coronal plane, posteriorly inclined in accordance with the MPTS on the sagittal plane, and 9 mm below the surface of the subchondral cortical bone (i.e., 11 mm below the surface of the cartilage) of the lateral tibial plateau. The association between the tibial morphology and the distance from the simulated cutting plane to the semimembranosus (SM) insertion (Dsm) was analyzed., Results: Of the 50 patients, 19 (38%) had negative Dsm values, indicating a cut into the SM (namely, below the posterior oblique ligament) insertion. The MPTS was negatively correlated with Dsm (r = -0.396, p = 0.004), whereas the CTS was positively correlated with Dsm (r = 0.619, p < 0.001). On multivariate linear regression analysis, the MPTS and CTS were independent predictors of Dsm., Conclusion: In the setting of tibial cuts reproducing the native MPTS in BCRTKA, patients with larger PTS and smaller CTS had more risk of trauma to the posteromedial structures., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Our institute has received donations for research from Smith & Nephew Japan KK. They played no role in the design of this study; in the collection, analysis, or interpretation of the data; or in the writing of this manuscript. The authors declare that they have no personal competing interest.], (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In bicruciate-stabilized total knee arthroplasty (BCS-TKA), the relationship between the postoperative kinematics and sports subscales in patient-reported outcome measures (PROMs) remains unknown. The purpose of this study was to determine the relationship between kinematics and sports subscales using the PROMs after BCS-TKA., Methods: Sixty-one patients with severe knee osteoarthritis were examined at 13.5 ± 7.8 months after BCS-TKA. The patients performed squats under single fluoroscopic surveillance in the sagittal plane. Range of motion of the knee, axial rotation of the femur relative to the tibial component, and anteroposterior (AP) translation of the medial and lateral femorotibial contact points were measured using a 2D-to-3D registration technique. In addition, the relationship between the kinematics and improvement of the sports subscales in the Knee Injury and Osteoarthritis Outcome Score (KOOS) was evaluated., Results: In rotation angle, the femoral external rotation was observed from 0 to 50° of flexion. The amount of femoral external rotation did not correlate with PROMs-SP. In medial AP translation, posterior translation was observed from 0 to 20° and 80-110° of flexion. Mild anterior translation was observed from 20 to 80° of flexion. Beyond 80° of flexion, posterior translation was positively correlated with squatting. In lateral AP translation, posterior translation was observed from 0 to 20° and 80-110° of flexion. Beyond 80° of flexion, posterior translation was positively correlated with running, jumping, twisting/pivoting, and kneeling., Conclusion: Femoral rollback at high flexion during squatting may be important to improve sports performance after BCS-TKA., (© 2022. The Author(s).)

Background: The choice of mobile bearing (MB) thickness is essential for obtaining successful results after mobile-bearing Oxford unicompartmental knee arthroplasty (UKA). This study aimed to investigate the effects of a 1-mm difference in bearing thickness on intraoperative MB movement and intraoperative knee kinematics in Oxford UKAs., Methods: We prospectively investigated the effects of a 1-mm difference in bearing thickness on intraoperative MB movement and knee kinematics in 25 patients who underwent Oxford UKAs when surgeons didn't know which bearing thickness to choose with 1-mm difference. A trial tibial component that was scaled every 2 mm was used to measure the intraoperative MB movement, and the tibial internal rotation relative to the femur and the knee varus angle was simultaneously evaluated using the navigation system as the knee kinematics. We separately evaluated sets of two MB thicknesses with 1-mm differences, and we compared the intraoperative parameters at maximum extension; 30º, 45º, 60º, and 90º flexion; and maximum flexion between the thicker MB (thick group) and the thinner MB (thin group)., Results: The MB in the thin group was located significantly posteriorly at 90º flexion compared with that in the thick group; however, there were no differences at the other flexion angles. There was significantly less tibial internal rotation in the thin group at 90º flexion than that in the thick group; however, there were no differences at the other flexion angles. The knee varus angles in the thick group were significantly smaller than those in the thin group by approximately one degree at all angles other than at 30º and 45º flexion., Conclusion: The thicker MB could bring the less posterior MB movement and the more tibial internal rotation at 90º flexion, additionally the valgus correction angle in the thicker MB should be paid attention. These results could help surgeons to decide the thickness of MBs when they wonder the thickness of MB., (© 2022. The Author(s).)

The Saccharomyces cerevisiae Trm11 and Trm112 complex (Trm11-Trm112) methylates the 2-amino group of guanosine at position 10 in tRNA and forms N 2 -methylguanosine. To determine the elements required in tRNA for methylation by Trm11-Trm112, we prepared 60 tRNA transcript variants and tested them for methylation by Trm11-Trm112. The results show that the precursor tRNA is not a substrate for Trm11-Trm112. Furthermore, the CCA terminus is essential for methylation by Trm11-Trm112, and Trm11-Trm112 also only methylates tRNAs with a regular-size variable region. In addition, the G10-C25 base pair is required for methylation by Trm11-Trm112. The data also demonstrated that Trm11-Trm112 recognizes the anticodon-loop and that U38 in tRNA Ala acts negatively in terms of methylation. Likewise, the U32-A38 base pair in tRNA Cys negatively affects methylation. The only exception in our in vitro study was tRNA Val AAC1 . Our experiments showed that the tRNA Val AAC1 transcript was slowly methylated by Trm11-Trm112. However, position 10 in this tRNA was reported to be unmodified G. We purified tRNA Val AAC1 from wild-type and trm11 gene deletion strains and confirmed that a portion of tRNA Val AAC1 is methylated by Trm11-Trm112 in S. cerevisiae . Thus, our study explains the m 2 G10 modification pattern of all S. cerevisiae class I tRNAs and elucidates the Trm11-Trm112 binding sites.

Purpose: The hypothesis of this study was that the kinematics of patients with higher patient-reported outcome measures (PROMs) differ from those of patients with lower PROMs after bicruciate-stabilized total knee arthroplasty (BCS-TKA)., Methods: A total of 32 patients with severe knee osteoarthritis were examined 11.2 ± 3.2 months after BCS-TKA. The patients performed squats under single fluoroscopic surveillance in the sagittal plane. To estimate the spatial position and orientation of the femoral and tibial components, a 2D-to-3D registration technique was used. This technique uses a contour-based registration algorithm, single-view fluoroscopic images and 3D computer-aided design models. Knee range of motion, varus-valgus alignment, axial rotation of the femur relative to the tibial component, anteroposterior translation of the medial and lateral femorotibial contact points, kinematic paths, and anterior and posterior post-cam engagement were measured. The patients were divided into two groups using hierarchical cluster analysis based on the 1-year postoperative Knee Injury and Osteoarthritis Outcome Score and 2011 Knee Society Score., Results: The femoral component had significantly more external rotation in the low-score group than in the high-score group (5.1 ± 1.8° vs. 2.2 ± 2.7°, p = 0.02). The high-score group had a medial pivot pattern from 0 to 20° of flexion, without significant movement from 20 to 70°, and final bicondylar rollback beyond 70°. The low-score group had a medial pivot from 0 to 70° of flexion and bicondylar rollback beyond 70°. There were no significant between-group differences in the varus-valgus angle or post-cam engagement., Conclusion: The higher PROM group had smaller external rotation of the femur after BCS-TKA., Level of Evidence: Level III., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: To evaluate the effect of weight-bearing on the kinematics of the bicruciate-retaining total knee arthroplasty design during high knee flexion activities., Methods: The kinematics of 21 bicruciate-retaining total knee arthroplasties were evaluated under fluoroscopy, with two- and three-dimensional image registrations, during squatting (weight-bearing) and active-assisted knee flexion (non-weight-bearing). The following variables were measured: knee range of motion, axis of femoral rotation and varus-valgus angle relative to the tibial component, anteroposterior translation of the medial and lateral contact points, and the kinematic pathway of the joint surfaces., Findings: From 20° to 100° of flexion, the femoral external rotation during weight-bearing was larger than that during non-weight-bearing. There were no differences in the varus-valgus angles between the two conditions. From 10° to 50° of flexion, the medial contact point during weight-bearing was located posterior to the point of contact during non-weight-bearing; this difference between the two weight-bearing conditions was significant. From 0° to 90° of flexion, the lateral contact point in weight-bearing was located posterior to the contact point in non-weight-bearing; this difference between the two weight-bearing conditions was also significant., Interpretation: The anteroposterior position of the medial and lateral contact points of the bicruciate-retaining total knee arthroplasty design was significantly more posterior in the mid-range of knee flexion in weight-bearing than in non-weight-bearing. However, no anterior translation of the bicruciate-retaining total knee arthroplasty design was observed. Therefore, bicruciate-retaining total knee arthroplasty appears to have good anteroposterior stability throughout the range of knee flexion, regardless of the weight-bearing condition., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Component gap (CG) measurement help surgeons evaluate intraoperative soft-tissue balance. One technique is measuring the CG using tensioner devices with distraction force. Another is to evaluate the laxity under a varus-valgus force using navigation or robotics. The aim was to compare the JL evaluated by CG and varus-valgus force between the different types of total knee arthroplasties., Methods: Forty-three bi-cruciate stabilized (BCS) knees and 33 bi-cruciate retaining (BCR) knees were included. After bone resection and soft tissue balancing, the CG was measured and after the final implantation and capsule closure, JL under a maximum varus-valgus stress was recorded with navigation. JL evaluated by the CG (JLCG) was defined as CG minus selected thickness of the tibial component and JL under varus-valgus force (JLVV) was defined as difference between varus-valgus angles without stress and maximum varus-valgus angles under varus-valgus force. The evaluations were performed at flexions of 10°, 30°, 60° and 90°., Results: Although JLCGs of lateral compartment of BCS were larger than those of BCR, no difference was found between JLVVs of BCS and BCR. Although JLCGs of lateral compartment did not change at each knee flexion angle in both BCS and BCR, JLVVs of lateral compartment increased by 3° from 10° to 90° knee flexion., Conclusion: JLVVs of BCS and BCR were equivalent, whereas BCS showed larger JLCGs of lateral compartment. JLVVs of lateral compartment increased by 3° in the range from 10° to 90° knee flexion whereas JLCGs remained stable., Competing Interests: Declaration of Competing Interest Our institute has received donations for research from Smith & Nephew Japan KK. They played no role in the design of this study; in the collection, analysis, or interpretation of the data; or in the writing of this manuscript. The authors declare that they have no personal competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aims at clarifying implant alignment and other patient factors' influence on clinical outcomes, particularly on patient-reported outcomes (PRO), following Oxford unicompartmental knee arthroplasty (OUKA). A total of 142 patients after OUKA were divided into two groups according to the validated Japanese version of the knee injury and osteoarthritis outcome score (KOOS) for each subscale of pain, symptoms, and activities of daily living (ADL) at postoperative year 1 and 2: group 1 had ≥80 scores and group 2 had <80 scores. Postoperative clinical and radiographical findings were then compared among groups in each subscale. Using postoperative year 1 and 2 data, a multivariable logistic regression analysis was conducted to clarify factors for clinical outcomes' improvement. In the analysis of KOOS subscale of symptoms at postoperative year 1, gender distribution, preoperative body mass index, and postoperative maximum knee flexion angles differed significantly among groups. In the analysis for KOOS subscale of ADL, significant differences were observed in postoperative tibial component varus angles. Multivariable logistic regression analysis revealed that all of these parameters significantly related to ≥80 KOOS scores of each subscale at postoperative year 1. Additionally, at postoperative year 2, larger postoperative knee flexion angles and tibial component varus angles related to ≥80 KOOS subscale of symptoms and ADL were observed. In conclusion, tibial component's larger varus alignment was associated with the better PRO at both 1 and 2 years after OUKA. Importantly, larger postoperative knee flexion angle helped achieve good short-term PRO after OUKA., Competing Interests: None declared., (Thieme. All rights reserved.)

The purpose of this study was to clarify the morphology of acute Achilles tendon rupture (ATR) according to intraoperative evaluation. The morphology of 220 cases was evaluated retrospectively from intraoperative findings from June 2014 to December 2015. We noted 3 characteristics of rupture. First, we divided the ruptures into complete or partial type. Second, according to the level of rupture, we classified them into muscle-tendon junctional type, mid-substantial type, or calcaneal insertional avulsion type. Lastly, on the basis of the pattern of rupture, we divided them into transverse pattern, double-layer pattern, or Z-shaped pattern. All ruptured tendons were repaired with surgical procedures on the basis of the classification of rupture type or pattern. Of the total of 220 cases, 217 were complete ruptures (98.7%) and 3 partial ruptures (1.3%). Regarding the level of rupture, 5 cases were of the muscle-tendon junctional type (2.3%), 209 cases of the mid-substantial type (95%), and 6 cases of the calcaneal insertional avulsion type (2.7%). In terms of the pattern of rupture, there were 198 cases of the transverse pattern (90%), 10 cases of the double-layer pattern (4.5%), and 12 cases of the Z-shaped pattern (5.5%). There was significant gender difference only in the mid-substantial type. Although the morphology of a typical acute ATR was complete, of mid-substance type, and with transverse pattern, other types of ATR were recognized from the intraoperative investigation., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to conduct a multivariate analysis to identify independent factors that predict tibial tunnel widening (TW) after anatomical anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BPTB) grafts., Methods: In total, 103 patients who underwent ACL reconstructions using BPTB grafts were included. Tunnel aperture area was measured using three-dimensional computed tomography 1 week and 1 year postoperatively, and the tibial TW was calculated. The patients were divided into group S comprising 58 patients who had tibial TW < 30% and group L comprising 45 patients who had tibial TW > 30%, retrospectively. Using univariate analyses, age, gender, body mass index, Tegner activity scale, the time between injury and surgery, tibial tunnel location, tibial tunnel angle, medial posterior tibial slope, lateral posterior tibial slope, and length of the tendon in the tibial tunnel were compared between two groups. Multivariate regression analysis was conducted to reveal the independent risk factors for the tibial TW among preoperative demographic factors and radiographic parameters that correlated with the tibial TW in the univariate analyses., Results: Compared with those at 1 week postoperatively, mean tibial tunnel aperture areas were increased by 30.3% ± 26.8% when measured at 1 year postoperatively. The lateral posterior tibial slope was significantly larger (p < 0.001), and the length of the tendon within the tibial tunnel was significantly longer in group L than that in group S (p = 0.03) in the univariate analyses. Multivariate regression analysis showed that the increase in lateral posterior tibial slope (p = 0.001) and the length of the tendon within the tibial tunnel (p = 0.03) were predictors of the tibial TW., Conclusions: This study showed that increased lateral posterior tibial slope and a longer tendinous portion within the tibial tunnel were independent factors that predicted the tibial TW following anatomical ACL reconstruction with a BPTB graft., Level of Evidence: III., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Tibial internal rotation following total knee arthroplasty (TKA) is important in achieving favorable postoperative clinical outcomes. Studies have reported the effect of intraoperative soft tissue balance on tibial internal rotation in conventional TKA, no studies have evaluated the effects of soft tissue balance at medial or lateral compartments separately on tibial internal rotation in bi-cruciate stabilized (BCS) TKA. The purpose of this study was to clarify the relationship between medial or lateral component gaps and rotational knee kinematics in BCS TKA., Methods: One hundred fifty-eight knees that underwent BCS TKA were included in this study. The intraoperative medial and lateral joint laxities which was defined as the value of component gap minus the thickness of the tibial component were firstly divided into two groups, respectively: Group M-stable (medial joint laxity, ≤ 2 mm) or Group M-loose (medial joint laxity, ≥ 3 mm) and Group L-stable (lateral joint laxity, ≤ 3 mm) or Group L-loose (lateral joint laxity, ≥ 4 mm). And finally, the knees enrolled in this study were divided into four groups based on the combination of Group M and Group L: Group A (M-stable and L-stable), Group B (M-stable and L-loose), Group C (M-loose and L-stable), and Group D (M-loose and L-loose). The intraoperative rotational knee kinematics were compared between the four Groups at 0°, 30°, 60°, and 90° flexion, respectively., Results: The rotational angular difference between 0° flexion and maximum flexion in Group B at 30° flexion was significantly larger than that in Group A at 30° flexion (*p < 0.05). The rotational angular difference between 30° flexion and maximum flexion in Group B at 30° flexion was significantly larger than that in Group D at 30° flexion (*p < 0.05). The rotational angular differences between 30° or 90° flexion and maximum flexion in Group B at 60° flexion were significantly larger than those in Group A at 60° flexion (*p < 0.05)., Conclusion: Surgeons should pay attention to the importance of medial joint stability at midflexion and lateral joint laxities at midflexion and 90° flexion on a good tibial internal rotation in BCS TKA., (© 2021. The Author(s).)

We analyzed the implantation effects on cruciate ligament force in unicompartmental knee arthroplasty (UKA) and determined whether kinematics is associated with the cruciate ligament force. We examined 16 patients (17 knees) undergoing medial UKA. Under fluoroscopy, each participant performed a deep knee bend before and after UKA. A two-dimensional/three-dimensional registration technique was employed to measure tibiofemoral kinematics. Forces in the anteromedial and posterolateral bundles of both the anterior cruciate ligament (aACL and pACL) and the anterolateral and posteromedial bundles of the posterior cruciate ligament (aPCL and pPCL) during knee flexion were analyzed pre- and post-UKA. Correlations between changes in kinematics and ligament forces post-UKA were also analyzed. Preoperatively, the aACL forces were highly correlated with anteroposterior (AP) translation of the lateral condyles (Correlation coefficient [r] = 0.59). The pPCL forces were highly correlated with the varus-valgus angulation (r =  - 0.57). However, postoperatively, the PCL forces in both bundles were highly correlated with the AP translation of the medial femoral condyle (aPCL: r = 0.62, pPCL: r = 0.60). The ACL and PCL forces of the knees post-UKA were larger than those of the knees pre-UKA. Kinematic changes were significantly correlated with the cruciate ligament force changes., (© 2021. The Author(s).)

Background: This study aimed to clarify potential gender differences across a comprehensive set of anthropometric and musculoskeletal characteristics within a young soccer player population., Methods: This study included 227 (121 males and 106 females with mean ages of 19.0 and 17.5 years, respectively) young elite soccer players. Anthropometric measurements were obtained. In addition, general joint laxity tests assessing the wrist, elbow, shoulder, trunk, hip, knee, and ankle were performed. Muscle flexibility tests were performed on the iliopsoas, quadriceps femoris, hamstring, gastrocnemius, and soleus muscles. Moreover, isometric knee extension and flexion strength and isometric hip abduction strength were measured. Single- and double-leg balance tests were also performed., Results: Male soccer players were taller, heavier, and had lower fat mass and percent body fat, and greater skeletal muscle mass and body minerals than female soccer players. Female soccer players had significantly greater laxity in all tests for general joint laxity. Female soccer players demonstrated significantly better hamstring and soleus flexibility than male soccer players but worse iliopsoas flexibility. Consequently, no significant differences were noticed in the quadriceps and gastrocnemius muscles between the male and female soccer players. However, female soccer players demonstrated significantly weaker knee extension and flexion and hip abduction. The hamstring- quadriceps ratio was significantly lower in female soccer players. Although no significant difference exists in the center of pressure excursion in the double-leg balance test between male and female soccer players, female soccer players displayed a significantly lower center of pressure excursion in the single-leg balance test., Conclusions: Young male and female soccer players demonstrate significantly different anthropometric and musculoskeletal profiles.