Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development.

During neocortical development, tight regulation of neurogenesis-to-astrogenesis switching of neural precursor cells (NPCs) is critical to generate a balanced number of each neural cell type for proper brain functions. Accumulating evidence indicates that a complex array of epigenetic modifications and the availability of extracellular factors control the timing of neuronal and astrocytic differentiation. However, our understanding of NPC fate regulation is still far from complete. Bone morphogenetic proteins (BMPs) are renowned as cytokines that induce astrogenesis of gliogenic late-gestational NPCs. They also promote neurogenesis of mid-gestational NPCs, although the underlying mechanisms remain elusive. By performing multiple genome-wide analyses, we demonstrate that Smads, transcription factors that act downstream from BMP signaling, target dramatically different genomic regions in neurogenic and gliogenic NPCs. We found that histone H3K27 trimethylation and DNA methylation around Smad-binding sites change rapidly as gestation proceeds, strongly associated with the alteration of accessibility of Smads to their target binding sites. Furthermore, we identified two lineage-specific Smad-interacting partners-Sox11 for neurogenic and Sox8 for astrocytic differentiation-that further ensure Smad-regulated fate-specific gene induction. Our findings illuminate an exquisite regulation of NPC property change mediated by the interplay between cell-extrinsic cues and -intrinsic epigenetic programs during cortical development.

Validity of a simple footprint assessment board for diagnosing the severity of flatfoot: a prospective cohort study.

BACKGROUND: A simple, non-quantitative, and cost-effective diagnostic tool would enable the diagnosis of flatfoot without need for specialized training. A simple footprint assessment board that investigates which toe the cord passes through from the centre point of the heel to the most lateral point of the medial contour of the footprint has been developed to assess flatfoot. The purpose of this study was to verify the validity of a simple footprint assessment board for flatfoot. METHODS: Thirty-five consecutive patients with foot pain, foot injury, or any associated symptoms who underwent computed tomography (CT) were analysed prospectively. At the time of the CT scan, a footprint analysis using a simple footprint assessment board was performed. The navicular index, tibiocalcaneal angle, and calcaneal inclination angle were evaluated by CT to assess flat feet. These three criteria were compared to those evaluated with the simple footprint assessment board by regression analysis. In addition, the same analysis was conducted separately for young, middle-aged, and older patients in order to investigate each age group. RESULTS: The navicular index and tibiocalcaneal angle generally decreased as the score of the simple footprint assessment board increased. Calcaneal inclination angle generally increased as the score of the simple footprint assessment board increased. As the scores of the simple footprint assessment board decreased by approaching the great toe, the navicular index and tibiocalcaneal angle were higher and calcaneal inclination angle was lower, which is indicative of a higher likelihood of flatfoot. The scores derived from the simple footprint assessment board was correlated with these three criteria measured by CT, not only when the result of simple footprint assessment board was set as a non-continuous variable but also when the result was set as a continuous variable. The results of the age-stratified survey were similar for all groups. CONCLUSIONS: The findings of this study suggest that a simple footprint assessment board can be potentially useful to detect flatfoot. TRIAL REGISTRATION: Retrospectively registered.

Epigenetic regulation for acquiring glial identity by neural stem cells during cortical development.

The nervous system consists of several hundred neuronal subtypes and glial cells that show specific gene expression and are generated from common ancestors, neural stem cells (NSCs). As the experimental techniques and molecular tools to analyze epigenetics and chromatin structures are rapidly advancing, the comprehensive events and genome-wide states of DNA methylation, histone modifications, and chromatin accessibility in developing NSCs are gradually being unveiled. Here, we review recent advances in elucidating the role of epigenetic and chromatin regulation in NSCs, especially focusing on the acquisition of glial identity and how epigenetic regulation enables the temporal regulation of NSCs during murine cortical development.

Periarticular multimodal drug injection does not improves early postoperative analgesia compared with continuous interscalene brachial plexus block after arthroscopic rotator cuff repair: A retrospective single-center comparative study.

BACKGROUND: Although continuous interscalene brachial plexus block (CISBPB) is common method in pain management following arthroscopic rotator cuff repair (ARCR), little is known about the analgesic effects of periarticular multimodal drug injection (PMDI) for ARCR. This retrospective study sought to clarify which technique could provide the best analgesic effect after ARCR. METHODS: We retrospectively reviewed consecutive patients who underwent ARCR performed by the same surgeon at our institution between June 2016 and November 2017. Patients who underwent surgery before January 2017 received CISBPB and those who underwent surgery after February 2017 received PMDI for postoperative pain control. Both treatment groups also received fentanyl by intravenous patient-controlled analgesia (IV-PCA). Postoperative pain was evaluated by visual analog scale (VAS) pain scores at 3, 6, 12, 24, and 48 h and need for IV-PCA at 8, 16, and 24 h. RESULTS: Twenty-eight patients received CISBPB and 21 received PMDI. According to the VAS scores, the postoperative analgesic effect was significantly better in the CISBPB group during the first 6 h (p < 0.05). Total fentanyl consumption by IV-PCA during the first 8 postoperative h was significantly greater in the PMDI group than in the CISBPB group. CONCLUSIONS: PMDI does not improve early postoperative analgesia after ARCR compared with CISBPB. CISBPB had a significantly better analgesic effect in the first 8 h postoperatively. LEVEL OF EVIDENCE: Level III.

Bone-to-bone integrations were complete within 5 months after anatomical rectangular tunnel anterior cruciate ligament reconstruction using a bone-patellar tendon-bone graft.

PURPOSE: Anterior cruciate ligament (ACL) reconstruction using a bone-patellar tendon-bone (BTB) graft is known to provide secure fixation due to the direct bone-to-bone integration of the bone plug and bone tunnel. It is important to know the time required for bone integration when designing the postoperative rehabilitation protocol or deciding when the patient can return to competition-level activity, especially if the patient is an athlete. However, because reports are scarce, the period necessary for bone-to-bone integration after ACL reconstruction using a BTB graft remains unclear. The purpose of this study was to clarify this issue. It was hypothesised that ACL reconstruction using a BTB graft via an anatomical rectangular tunnel would help in the integration between bone plugs and bone tunnels on both the femoral and tibial sides after at least 6 months, at which point basic exercises similar to pre-injury sporting activity levels can be resumed. METHODS: This study included 40 knees treated with ACL reconstruction using a BTB graft via anatomical rectangular tunnel reconstruction between 2013 and 2014 in a single institute. The integration between bone plugs and bone tunnels was evaluated using multi-slice tomosynthesis, which is a technique for producing slice images using conventional radiographic systems, at 1, 3, and 5 months postoperatively. All procedures were performed by two experienced surgeons. Bone integration was evaluated by two orthopaedic doctors. RESULTS: The rates of integration of the bone plug and femoral bone tunnel on tomosynthesis at 1, 3, and 5 months postoperatively were 0, 55, and 100%, respectively. On the tibial side, the corresponding rates were 0, 75, and 100%, respectively. The rate of integration on the tibial side was significantly higher than that on the femoral side at 3 months postoperatively (p = 0.031). CONCLUSIONS: Bone-to-bone integration on the femoral and tibial sides was complete within 5 months after surgery in all cases. Since the time required for bone integration is important in designing the postoperative rehabilitation approach, these results will serve as a useful guideline for planning rehabilitation protocols. LEVEL OF EVIDENCE: IV.

Surgical timing of anterior cruciate ligament reconstruction to prevent associated meniscal and cartilage lesions.

BACKGROUND: The purpose of this study was to analyze the association between the prevalence of meniscal and chondral lesions and the timing of surgery in patients undergoing primary anterior cruciate ligament (ACL) reconstruction to determine a safe time for surgery. METHODS: This retrospective study involved 226 patients (91 females and 135 males; median age, 29 years) undergoing primary ACL reconstruction. Time interval from ACL injury to surgery (median, 4 months; range, 1-420 months) and concomitant meniscal and cartilage lesions in ACL reconstruction were reviewed. Receiver operating characteristic (ROC) curve analysis was used to determine the precise threshold interval to surgery to prevent meniscal or cartilage lesions. The risk of lesion occurrence after each cutoff period was determined using odds ratio (OR). RESULTS: The incidences of medial meniscus (MM), lateral meniscus (LM), and cartilage lesions were 43.8%, 32.7%, and 27.4%, respectively. ROC analysis revealed that patients who waited for more than 6, 4, and 5 months for ACL reconstruction had a significantly greater risk of associated MM, LM, and chondral lesions, respectively. Patients who underwent ACL reconstruction ≥7 months after injury had OR of 4.1 (p < 0.001) for the presence of MM lesion as compared with those who underwent reconstruction within 6 months. Similarly, patients who underwent ACL reconstruction ≥5 months after injury had OR of 1.9 (p = 0.023) for the presence of LM lesion as compared with those who underwent reconstruction within 4 months, and patients who underwent ACL reconstruction ≥6 months after injury had OR of 2.9 (p < 0.001) for chondral lesion as compared with those who underwent reconstruction within 6 months. CONCLUSION: ACL reconstruction should be performed within approximately 6 months after the injury to prevent associated meniscal or chondral lesions.

Effects of initial graft tension on femoral tunnel widening after anatomic anterior cruciate ligament reconstruction using a bone-patellar tendon-bone graft.

INTRODUCTION: The effects of initial graft tension upon tunnel widening (TW) following anatomic anterior cruciate ligament (ACL) reconstruction have not been elucidated. The purpose of this study was to retrospectively investigate the effect of two different graft-tensioning protocols upon femoral TW following anatomic ACL reconstruction using a bone-patellar tendon-bone (BPTB) graft and a three-dimensional (3D) computed tomography (CT) model. METHODS: Forty-three patients who underwent isolated ACL reconstruction using BPTB grafts were included in this study. In 18 out of the 43 patients, the graft was fixed at full knee extension with manual maximum pull (Group H). These patients were compared with 25 patients in whom the BPTB graft was fixed at full knee extension with 80-N pull (Group L). Tunnel aperture area was measured using 3D CT 1 week and 1 year postoperatively, thus enabling us to calculate the percentage change in the area of femoral tunnel aperture. Clinical assessment was performed 1 year postoperatively, corresponding to the time period of CT assessment, and involved the evaluation of Lysholm score, anterior knee stability using a KneeLax3 arthrometer, and the pivot-shift test. RESULTS: When measured at 1 year postoperatively, the mean area of the femoral tunnel aperture had increased by 78.6 ± 36.8% in Group H when compared with at 1 week postoperatively, whereas that of Group L had increased by 27.7 ± 32.3%. Furthermore, TW (%) in Group H was significantly greater than that of Group L (P < 0.001). No significant differences were detected between the two groups with regard to any of the clinical outcomes evaluated. CONCLUSION: High levels of initial graft tension resulted in greater TW of the femoral tunnel aperture following anatomical ACL reconstruction using BPTB grafts. However, such levels of graft tension did not affect clinical outcome.

C/EBPß and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2α as the inducer in chondrocytes.

To elucidate the molecular mechanism underlying the endochondral ossification process during the skeletal growth and osteoarthritis (OA) development, we examined the signal network around CCAAT/enhancer-binding protein-ß (C/EBPß, encoded by CEBPB), a potent regulator of this process. Computational predictions and a C/EBP motif-reporter assay identified RUNX2 as the most potent transcriptional partner of C/EBPß in chondrocytes. C/EBPß and RUNX2 were induced and co-localized in highly differentiated chondrocytes during the skeletal growth and OA development of mice and humans. The compound knockout of Cebpb and Runx2 in mice caused growth retardation and resistance to OA with decreases in cartilage degradation and matrix metalloproteinase-13 (Mmp-13) expression. C/EBPß and RUNX2 cooperatively enhanced promoter activity of MMP13 through specific binding to a C/EBP-binding motif and an osteoblast-specific cis-acting element 2 motif as a protein complex. Human genetic studies failed to show the association of human CEBPB gene polymorphisms with knee OA, nor was there a genetic variation around the identified responsive region in the human MMP13 promoter. However, hypoxia-inducible factor-2α (HIF-2α), a functional and genetic regulator of knee OA through promoting endochondral ossification, was identified as a potent and functional inducer of C/EBPß expression in chondrocytes by the CEBPB promoter assay. Hence, C/EBPß and RUNX2, with MMP-13 as the target and HIF-2α as the inducer, control cartilage degradation. This molecular network in chondrocytes may represent a therapeutic target for OA.

Eccentric femoral tunnel widening in anatomic anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study was to retrospectively evaluate femoral tunnel widening (TW) and migration of the femoral tunnel aperture after anatomic anterior cruciate ligament (ACL) reconstructions with hamstring grafts and bone-patellar tendon-bone (BPTB) grafts. METHODS: Of the 105 consecutive patients who underwent ACL reconstruction, the 52 patients who underwent isolated ACL reconstruction and in whom tunnel measurement could be obtained by computed tomography were included in this study. In 26 patients, double-bundle reconstruction (DBR) of the ACL using hamstring tendons was performed. These patients were compared with 26 patients in whom rectangular tunnel ACL reconstruction using BPTB grafts (BPTBR) was performed. Femoral tunnel aperture positioning and TW were investigated postoperatively using 3-dimensional computed tomographic images, which were performed a week and a year after surgery in all patients. RESULTS: In DBR, the average diameter of the anteromedial (AM) femoral tunnel increased by 34.0% in the horizontal direction and 28.2% in the vertical direction, whereas that of the posterolateral (PL) femoral tunnel increased by 58.2% and 73.4%, respectively, at 1 year after surgery compared with 1 week after surgery. The percentage TW value of the PL tunnel was significantly greater than that of the AM tunnel. In BPTBR, the average diameter increased by 22.0% and 17.1%, respectively. The percentage TW value of the PL tunnel in DBR was significantly greater than that of the femoral tunnel in BPTBR. Each tunnel aperture migrated distally ("shallow") in the horizontal direction and high in the vertical direction. AM and PL tunnel apertures in DBR migrated in the vertical direction significantly more than they did in BPTBR. No significant differences between the 2 groups were found in clinical outcomes. CONCLUSIONS: The femoral PL tunnel aperture in DBR showed significantly more widening than did the AM tunnel aperture in DBR and the femoral tunnel aperture in BPTBR. Also, greater migration of the femoral tunnel aperture in the vertical direction because of TW was observed in DBR than in BPTBR. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Clinical outcome of anatomic double-bundle ACL reconstruction and 3D CT model-based validation of femoral socket aperture position.

PURPOSE: The purpose of this study was to evaluate the clinical results of anatomic double-bundle (DB) anterior cruciate ligament (ACL) reconstruction in which anatomic position of femoral socket apertures was validated using three-dimensional (3D) computed tomography (CT) modelling. METHODS: Anatomic DB ACL reconstructions with hamstring autografts were performed in 34 patients. Two femoral sockets were created through a far anteromedial (AM) portal behind the lateral intercondylar ridge with the assistance of intraoperative 3D fluoroscopic navigation. Femoral tunnel aperture positioning was investigated postoperatively using 3D CT images in all patients. Clinical results were also evaluated subjectively and objectively at least up to 2 years. RESULTS: Measurement of the AM and the posterolateral (PL) femoral socket locations on the 3D CT images using the quadrant method showed that the centre of the AM socket aperture was located at a depth of 21.0 ± 4.1% and a height of 30.5 ± 9.3% and that of the PL socket aperture was located at a depth of 31.3 ± 5.8% and a height of 57.2 ± 7.7%. The femoral socket locations were considered as anatomic in accordance with previous cadaveric studies examining the positions of ACL femoral insertion site. Subjectively, the mean Lysholm score was 96.9 ± 4.0 points. According to IKDC final objective scores, 26 knees (76%) were objectively graded as normal, 8 (24%) as nearly normal, and 0 (0%) as abnormal or severely abnormal. Postoperative side-to-side anterior translation measured with a KT-2000 arthrometer averaged 0.7 ± 1.2 mm. CONCLUSIONS: DB ACL reconstructions in which femoral socket apertures were validated anatomically using 3D CT provided satisfactory short-term results. LEVEL OF EVIDENCE: Case series, Level IV.

Kinematic Alignment Achieves a More Balanced Total Knee Arthroplasty Than Mechanical Alignment among CPAK Type I Patients: A Simulation Study.

Background: There is no consensus on whether mechanical alignment (MA) or kinematic alignment (KA) should be chosen for total knee arthroplasty (TKA) for coronal plane alignment of the knee (CPAK) Type I with a varus arithmetic HKA (aHKA) and apex distal joint line obliquity (JLO). The aim of this study was to investigate whether MA or KA is preferable for soft tissue balancing in TKA for this phenotype. Method: This prospective cohort study included 64 knees with CPAK Type I osteoarthritis that had undergone cruciate-retaining TKA. Using optical tracking software, we simulated implant placement in the Mako system before making the actual bone cut and compared the results between MA and KA. Extension balance (the difference between medial and lateral gaps in extension) and medial balance (the difference in medial gaps in flexion and extension) were examined. These gap differences within 2 mm were defined as good balance. Achievement of overall balance was defined as an attainment of good extension and medial balance. The incidence of balance in each patient was compared with an independent sample ratio test. Results: Compared with the MA group, the KA group achieved better soft tissue balance in extension balance (p < 0.001). A total of 75% of the patients in the KA group achieved overall balance, which was greater than the 38% achieved in the MA group (p < 0.001). Conclusions: In robot-assisted TKA for CPAK Type I osteoarthritis, KA achieved knee balance during extension without soft tissue release in a greater percentage of patients than MA.

SOX11 contributes to the regulation of GDF5 in joint maintenance.

BACKGROUND: Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis. RESULTS: Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5' UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans. CONCLUSIONS: This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis.

Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice.

OBJECTIVE: To investigate the chondroprotective effect of cyclooxygenase 2 (COX-2) inhibition in experimental osteoarthritis (OA). METHODS: The expression of prostaglandin E2 synthetic enzymes was examined by immunostaining of tibial cartilage from mice with surgically induced knee joint instability and from OA patients undergoing total knee arthroplasty. The effect of orally administered celecoxib (10 mg/kg/day and 30 mg/kg/day) or vehicle alone in mice was examined 12 weeks after the induction of OA. To investigate the involvement of COX-1 and COX-2 in OA development, we also created the model in COX-1-homozygous-knockout (Ptgs1-/-) mice and COX-2-homozygous-knockout (Ptgs2-/-) mice. OA severity was assessed using a grading system developed by our group and by the Osteoarthritis Research Society International scoring system. RESULTS: In mouse and human OA cartilage, the expression of the inducible enzymes COX-2 and microsomal prostaglandin E synthase 1 (mPGES-1) was enhanced, while that of the constitutive enzymes COX-1, cytosolic PGES, and mPGES-2 was suppressed. Daily celecoxib treatment did not prevent cartilage degradation or osteophyte formation during OA development in the mouse model. Furthermore, neither Ptgs1-/- mice nor Ptgs2-/- mice exhibited any significant difference in OA development as compared to wild-type littermates. CONCLUSION: The two COX enzymes differ in terms of regulation of their expression during OA development. Nevertheless, experiments using inhibitor and genetic deficiency demonstrated a lack of chondroprotective effect of COX-2 inhibition in the mouse surgical OA model.

Restoration of sagittal and transverse plane proprioception following anatomic double-bundle ACL reconstruction.

PURPOSE: To investigate the restoration of knee proprioception after anatomic double-bundle ACL reconstruction. METHODS: Eleven subjects who underwent anatomic double-bundle ACL reconstruction (12.5-15 months following surgery) and eleven healthy control subjects participated in the study. Sagittal and transverse plane threshold to detect passive motion (TTDPM) were assessed utilizing a customized isokinetic dynamometer by passively rotating the tibia about a fixed femur in both the sagittal plane and transverse plane at 0.25°/s until the subject signalled recognition of movement and movement direction. Based on the normality assumption, either dependent t test or Wilcoxon test was utilized to determine whether significant differences were present between the ACL-reconstructed and the uninjured contralateral limbs. Independent t test or Mann-Whitney test was utilized to compare between the ACL-reconstructed/uninjured contralateral and the external control limbs. RESULTS: There were no significant differences in TTDPM measurement in eleven out of twelve comparisons between the ACL-reconstructed and the uninjured contralateral/external control limbs. The only statistical significant difference was found on TTDPM towards internal rotation direction from the externally rotated-test position between the ACL-reconstructed and the uninjured contralateral limbs (p = 0.01). CONCLUSIONS: Based on a small sample of eleven subjects, the current results indicate a restoration of both sagittal and transverse plane TTDPM following the anatomic double-bundle ACL reconstruction. LEVEL OF EVIDENCE: III.

An additional reference axis improves femoral rotation alignment in image-free computer navigation assisted total knee arthroplasty.

Few studies have demonstrated improvement in accuracy of rotational alignment using image-free navigation systems mainly due to the inconsistent registration of anatomical landmarks. We have used an image-free navigation for total knee arthroplasty, which adopts the average algorithm between two reference axes (transepicondylar axis and axis perpendicular to the Whiteside axis) for femoral component rotation control. We hypothesized that addition of another axis (condylar twisting axis measured on a preoperative radiograph) would improve the accuracy. One group using the average algorithm (double-axis group) was compared with the other group using another axis to confirm the accuracy of the average algorithm (triple-axis group). Femoral components were more accurately implanted for rotational alignment in the triple-axis group (ideal: triple-axis group 100%, double-axis group 82%, P<0.05).

Fifth metatarsal strain distribution during cutting motions in soccer.

The objective of this study was to determine the fifth metatarsal strain generation mechanism during cutting motions performed while playing soccer using a finite element foot model. Five collegiate soccer players performed the side-step cutting and the cross-step cutting motions to measure the three-dimensional foot kinematics, ground reaction force, and plantar pressure distribution. In addition, a finite-element model of a foot consisting of bony structures, ligaments, and skin was constructed from computed tomography images. Simulations were conducted to perform the cutting motions, using the measured foot motion and distributed load on the plantar surface as boundary conditions for the model. During the side-step cutting, the maximum principal strain on the fifth metatarsal was correlated to forefoot adduction angle during stepping out. For cross-step cutting, the maximum principal strain was correlated with plantar pressure at the distal end of the fifth metatarsal. Therefore, to prevent a fracture, it is necessary to take measures to reduce the lateral bending deformation of the forefoot while stepping out during side-step cutting and to reduce the plantar pressure on the distal end of the fifth metatarsal during cross-step cutting.

Correction of Varus Alignment with Peripheral Osteophyte Removal during Total Knee Arthroplasty: An Assessment with Computer Navigation.

Techniques for symmetrical balancing in flexion and extension have been described; however, the ideal technique is unclear. This study aimed to clarify whether resection of peripheral osteophytes could restore neutral hip-knee-ankle (HKA) angle of varus deformity of arthritic knees. Data from 90 varus arthritic knees that had undergone total knee arthroplasty (TKA) using a nonimage-based navigation system were analyzed. The change in the coronal mechanical axis, while applying manual valgus stress at extension and 90 degrees of knee flexion, was recorded after the following sequential procedures: (1) anterior cruciate ligament (ACL) sectioning, (2) subperiosteal stripping of the deep medial collateral ligament (MCL) from the underlying osteophytes on the medial tibia, and (3) complete removal of peripheral osteophytes from the proximal medial tibia and distal medial femoral condyle. Repeated measures of analysis of variance (ANOVA) were performed to compare the varus angle among each step, and a post hoc analysis by paired t-test was utilized to compare the parameters between baseline and each step. The varus alignment with valgus stress at extension and 90 degrees of flexion (mean: 6.0 ± 3.6 and 5.2 ± 3.9 degrees of varus, respectively) was significantly corrected to a near-neutral mechanical axis (mean: 0.9 ± 2.4 and 1.4 ± 4.2 degrees of varus, respectively) after peripheral osteophyte resection (p < 0.01, both). In many cases, varus deformity of arthritic knees could be corrected to near-neutral HKA angle by applying manual valgus stress after complete peripheral osteophyte resection. These procedures could facilitate soft tissue balancing in TKA, minimizing the risk of overrelease of the medial soft tissues.

Distribution of Coronal Plane Alignment of the Knee Classification in Patients with Knee Osteoarthritis in Japan.

Coronal plane alignment of the knee (CPAK) has recently been proposed as a simple and universal classification system to determine the suitability of a particular phenotype of the knee to a specific alignment strategy for knee replacement surgery. Although racial differences may affect knee alignment, there are no reports on the racial distribution of this classification system. We aimed to clarify the distribution of CPAK classification in patients with osteoarthritis who underwent total knee arthroplasty (TKA) in Japan. Consecutive patients who underwent primary TKA were analyzed retrospectively. The knees were categorized according to the CPAK classification system which comprised of two independent variables (arithmetic hip-knee-ankle [aHKA] angle and joint-line obliquity [JLO]) with three respective subgroups to create the following nine phenotypes of the knee: type I (varus aHKA and apex distal JLO), type II (neutral aHKA and apex distal JLO), type III (valgus aHKA and apex distal JLO), type IV (varus aHKA and neutral JLO), type V (neutral aHKA and neutral JLO), and type VI (valgus aHKA and neutral JLO), type VII (varus aHKA and apex proximal), type VIII (neutral aHKA and apex proximal), and type IX (valgus aHKA and apex proximal). The distribution of the phenotypes in the Japanese population was investigated as a primary outcome. To accurately compare the results with previous studies conducted on non-Japanese patients, a sex-matched distribution was investigated as a secondary outcome. A total of 570 knees were investigated of which 500 knees were examined after exclusions. The most common distribution was type I (53.8%), followed by type II (25.4%), type III (8.2%), type IV (7.2%), type V (4.4%), and type VI (1.0%). Types VII, VIII, and IX were not distributed. The sex-matched distribution was nearly identical to the overall distribution in Japan. The majority of patients with knee osteoarthritis in Japan had medially tilted joints with constitutional varus alignment.

Experimental Study on Inspiratory Phonation Using Physical Model of the Vocal Folds.

In inspiratory phonation, the air is inhaled from the mouth. The inhaled air passes through the glottis towards the lungs, thereby inducing the vocal fold vibrations. Such phonation takes place in various situations such as sighs, laughter, and crying. To characterize the inspiratory phonation, an experimental study was carried out using a physical model of the vocal folds. By reversing the direction of the airflow that passed through the vocal fold model, the inspiratory phonation was experimentally realized and compared with the normal expiratory phonation. Our experiments revealed that the phonation threshold pressures as well as the volume flow rates decreased under the inspiratory condition. Accordingly, the vocal efficiency was increased. The fundamental frequency was also increased under the inspiratory condition. The kymograms showed that phase of the upper edge of the vocal fold advanced that of the lower edge under the inspiratory phonation. A mathematical model of the vocal folds was further constructed to elucidate these experiments. Except for few aspects, our experimental findings are in good agreement with the preceding studies on inspiratory phonation (e.g., reversed propagation of the mucosal waves observed in a singer, increased pitches in human subjects, and use of inspiratory phonation in speech therapy).

Assessing the Role of Minimal Medial Tissue Release during Navigation-Assisted Varus Total Knee Arthroplasty Based on the Degree of Preoperative Varus Deformity.

We assessed the impact of a minimal medial soft-tissue release with complete peripheral osteophyte removal on the ability to attain manual preresection deformity correction during navigation-assisted total knee arthroplasty (TKA) for varus osteoarthritis. We included 131 TKAs for 109 patients with medial compartment predominant osteoarthritis. The steps for achieving minimal medial soft-tissue release were performed as follows: (1) elevation of a periosteal sleeve to 5-mm distal to the joint line and (2) complete removal of peripheral osteophytes. The evaluation criteria of this study were as follows: (1) age, (2) height, (3) weight, (4) body mass index (BMI), (5) sex, (6) the preoperative femorotibial mechanical angle in the neutral position before medial release and (7) the mechanical angle in maximum manual valgus stress after the two-step medial-release procedure (measured on the navigation screens). Multiple regression analysis of the criteria was performed to determine the degree of varus deformity that allowed neutral alignment but required extensive medial release. The femorotibial mechanical angle in the neutral position before medial release and sex correlated with the mechanical angle in maximum manual valgus stress on the navigation screen after medial release (r = 0.72, p < 0.001). Based on the regression formula, the maximum degree of preoperative varus deformity that allowed neutral alignment by the minimum medial-release procedure was 5.3 degrees for males and 9.1 degrees for females. The magnitude of deformity which has an impact on the ability to correct varus deformity (by minimal soft-tissue release and complete osteophyte removal) was clarified. If the preoperative degree of varus deformity was within 5.3 degrees for males and 9.1 degrees for females, an extensive medial release was not required to obtain neutral alignment.