A large preoperative pelvic oblique angle affects perception of leg length discrepancy after total hip arthroplasty.

BACKGROUND: In some cases, patients feel a perceived leg length discrepancy (P-LLD) despite no radiographic leg length discrepancy (R-LLD) after total hip arthroplasty (THA). We aimed to investigate the rate of postoperative P-LLD and the factors that cause postoperative P-LLD. METHODS: A retrospective study was conducted on 100 patients with R-LLD ≤5 mm after THA. Patients were classified into two groups based on P-LLD post-THA: group P (with P-LLD) and group E (without P-LLD). Relevant data on the general characteristics and radiological findings between the two groups were compared. RESULTS: We observed that 25 & 75% of patients belonged to group P and group E, respectively, with no significant difference in patient background. Postoperative Japanese Orthopedic Association (JOA) classification of pain and activities of daily living scores were significantly lower in group P than in group E (37.2 ± 3.9 vs. 39.1 ± 2.2, respectively; P = 0.013, and 16.2 ± 4.2 vs. 18.2 ± 2.2, respectively; P = 0.011). The preoperative pelvic oblique angle (POA) was significantly larger in group P than in group E (3.3 ± 2.3° vs. -0.2 ± 2.1°; respectively; P < 0.01). The pelvis tilted toward the surgical side was significantly higher in group P than in group E(88% vs 57%; respectively; P = 0.013). The preoperative C7 coronal vertical axis (C7 CVA) was significantly larger in group P than in group E (6.7 ± 14.7 mm vs. -0.2 ± 10.3 mm; respectively; P = 0.028). Multivariate logistic analysis revealed that preoperative POA (OR, 3.71; 95% CI: 1.86-8.12; P < 0.01) and the pelvis tilted toward the surgical side (OR, 4.14; 95% CI: 2.07-9.71; P = 0.022) were independent risk factors for P-LLD after THA. CONCLUSION: Even though there was no postoperative R-LLD, 25% of patients had P-LLD. A large preoperative POA and the pelvis tilted toward the surgical side were independent risk factors for P-LLD after THA.

The role of ROC75 as a daytime component of the circadian oscillator in Chlamydomonas reinhardtii.

The circadian clocks in chlorophyte algae have been studied in two model organisms, Chlamydomonas reinhardtii and Ostreococcus tauri. These studies revealed that the chlorophyte clocks include some genes that are homologous to those of the angiosperm circadian clock. However, the genetic network architectures of the chlorophyte clocks are largely unknown, especially in C. reinhardtii. In this study, using C. reinhardtii as a model, we characterized RHYTHM OF CHLOROPLAST (ROC) 75, a clock gene encoding a putative GARP DNA-binding transcription factor similar to the clock proteins LUX ARRHYTHMO (LUX, also called PHYTOCLOCK 1 [PCL1]) and BROTHER OF LUX ARRHYTHMO (BOA, also called NOX) of the angiosperm Arabidopsis thaliana. We observed that ROC75 is a day/subjective day-phase-expressed nuclear-localized protein that associates with some night-phased clock genes and represses their expression. This repression may be essential for the gating of reaccumulation of the other clock-related GARP protein, ROC15, after its light-dependent degradation. The restoration of ROC75 function in an arrhythmic roc75 mutant under constant darkness leads to the resumption of circadian oscillation from the subjective dawn, suggesting that the ROC75 restoration acts as a morning cue for the C. reinhardtii clock. Our study reveals a part of the genetic network of C. reinhardtii clock that could be considerably different from that of A. thaliana.

Hip function in patients undergoing conservative treatment for osteonecrosis of the femoral head.

PURPOSE: Once collapsed, osteonecrosis of the femoral head (ONFH) generally obtains collapse cessation naturally and surgical intervention can be avoided in the long term. This study aimed to investigate the process of hip function and secondary osteoarthritis changes in ONFH patients undergoing conservative treatment. METHODS: We included 54 patients with symptomatic ONFH at the first visit with a minimum follow-up of three years with conservative treatment. Patients were divided into two groups based on collapse cessation < 3 mm (stable group) or progression to > 3 mm (progression group). Additionally, we investigated age, sex, body mass index (BMI), etiology, contralateral side hip joint, the Japanese Investigation Committee (JIC) type classification, Harris hip score (HHS), Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), and survival rate with secondary osteoarthritis as the endpoint. RESULTS: The stable and progression groups had 31 and 23 patients, respectively. No significant differences in age, sex, BMI, and aetiology were observed between the two groups, except for the contralateral side hip joint and JIC type classification. The HHS and JHEQ were significantly improved at the final follow-up than at the first visit in the stable group. However, there were no significant differences in HHS and JHEQ at the final follow-up than at the first visit in the progression group. The five year survival rates with secondary osteoarthritis as the endpoint were significantly higher in the stable group (100%) than in the progression group (32.5%). CONCLUSION: Hip joint function improved by continuing conservative treatment in ONFH patients with collapse cessation < 3 mm.

Factors affecting sports participation after total hip arthroplasty.

PURPOSE: The purpose of this study was to investigate the rate of return to sports after total hip arthroplasty (THA) in patients who regularly participate in sports and evaluate the factors that can affect the return to sports. METHODS: In total, 165 patients who had been continuously participating in sports prior to surgery were included from a total of 401 patients who underwent THA from 2015 to 2018. The mean follow-up was 3.3 (range, 2-6) years. Demographics, medical history, surgical parameters, functional outcomes, and anxiety about complications at the final follow-up were compared between the patients who participated in the same sports as before surgery (S group) and those who could not (N group). RESULTS: The overall return to sports rate was 79% for 68 (41%) and 97 (59%) patients in the S and N groups, respectively. The most common sports that patients participated in post-operatively were walking (76 patients, 46%) and swimming (37 patients, 22%), followed by muscle training (25 patients, 15%). There were significant differences between the groups in the following patient factors: sex, primary disease, post-operative Japanese Orthopedic Association Hip-Disease Evaluation Questionnaire outcome, and anxiety about falls and dislocation. In the evaluation of factors affecting return to sports using logistic regression analysis, male sex (odds ratio 3.66, 95% confidence interval 1.13-11.19, p = 0.029) and anxiety of dislocation (odds ratio 3.42, 95% confidence interval 1.58-7.42, p < 0.01) were extracted as independent risk factors. CONCLUSION: Careful patient guidance and rehabilitation, in addition to accurate surgical procedures, will improve patient participation in sports.

Gain-of-Function of FGFR3 Accelerates Bone Repair Following Ischemic Osteonecrosis in Juvenile Mice.

Bone collapse, bone deformity, and a long treatment period are major clinical problems associated with juvenile ischemic osteonecrosis (JIO). Accelerating the process of bone repair in JIO is expected to shorten the treatment duration and better maintain morphology. We previously indicated that both bone formation and resorption were accelerated following distraction osteogenesis-mediated limb lengthening in genetically engineered mutant mice with a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR3) gene (i.e., Fgfr3 mice). The purpose of this study was to investigate the role of FGFR3 in the bone repair process following surgically induced ischemic osteonecrosis in the mutant mice. Epiphyseal deformity was less in the Fgfr3 mice compared to the wild-type mice at 6 weeks following ischemic osteonecrosis in skeletally immature age. Assessment of the morphology by micro-computed tomography (CT) revealed that the trabecular bone volume was increased in the Fgfr3 mice. Dynamic bone histomorphometry revealed increased rates of bone formation and mineral apposition in the Fgfr3 mice at 4 weeks post-surgery. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells rapidly increased, and the numbers of TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells rapidly decreased in the Fgfr3 mice. Vascular endothelial growth factor (VEGF) expression was increased at the earlier phase post-surgery in the Fgfr3 mice. The activation of FGFR3 signaling shortens the time needed for bone repair after ischemic osteonecrosis by accelerating revascularization, bone resorption, and new bone formation. Our findings are clinically relevant as a new potential strategy for the treatment of JIO.

Factors influencing inconsistent leg length discrepancy in dysplastic hip osteoarthritis: a retrospective study.

BACKGROUND: We aimed to examine the inconsistency between radiographic leg length discrepancy (R-LLD) and perceived LLD (P-LLD) in patients with dysplastic hip osteoarthritis and to evaluate the factors that can cause such inconsistency. METHODS: We conducted a retrospective study on 120 patients. An inconsistent LLD was defined as a condition in which the P-LLD was shorter than the R-LLD by > 5 mm. We compared relevant data on the general characteristics of the patients and the radiological findings between consistent (group E, 92 cases [76.7%]) and inconsistent LLDs (group S, 28 cases [23.3%]). RESULTS: The number of patients with a history of hip surgery on the affected side and the Japanese Orthopedic Association classification pain scores were significantly higher in group S than in group E (32.1% vs. 10.8%, respectively; P = 0.015, and 21.7 ± 7.0 vs. 17.5 ± 8.2, respectively; P = 0.036). The pelvic oblique angle and length of the R-LLD were significantly higher in group S than in group E (2.9 ± 2.5° vs. 0.3 ± 2.3°, respectively; P < 0.01, and 17.2 ± 8.9 mm vs. 6.3 ± 8.4 mm, respectively; P < 0.01). Multivariate logistic analysis revealed that the pelvic oblique angle (odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.28-2.52; P < 0.01) and length of the R-LLD (OR: 2.75, 95% CI: 1.24-6.12; P = 0.013) were independent risk factors of inconsistent LLD. CONCLUSION: The pelvic oblique angle and a long R-LLD were independent risk factors of inconsistent LLD in patients with dysplastic hip osteoarthritis. Therefore, hip surgeons should consider P-LLD rather than R-LLD to understand the need for conservative intervention.

Association between locomotive syndrome and fall risk in the elderly individuals in Japan: The Yakumo study.

BACKGROUND: Patients with locomotive syndrome (LS) are poor ambulatory status and a high risk of requiring nursing care. The purpose of this study is to investigate the relationship between LS and fall risk among community-dwelling elderly individuals. METHODS: The subjects were Japanese elderly individuals aged 65 and over who participated in Yakumo study 2019 (N = 189). We defined the fall risk index 5 items version (FRI-5) ≥6 points as the fall risk group. LS was evaluated by stand-up test, two-step test, and 25-Geriatric Locomotive Function Scale (GLFS-25). We divided the subjects into two groups according to the presence or absence of fall risk, and investigated factors associated with fall risk. RESULTS: The fall risk group (30 patients, 15.9%) had higher GLSF-25 (P = 0.001). The results of logistic regression analysis adjusted for age, sex, BMI, and knee osteoarthritis revealed that GLFS-25 (OR: 1.052; 95%CI: 1.009-1.097) was independent factor associated with fall risk. In the ROC analysis, the optimal cut-off value of the GLFS-25 to predict fall risk was 12, which is equivalent to LS stage 1 (AUC 0.688; 95% CI: 0.588-0.787; sensitivity: 0.467, specificity: 0.836). CONCLUSIONS: GLFS-25 was associated with fall risk among community-dwelling elderly individuals aged 65 and over.

Phase-resetting mechanism of the circadian clock in Chlamydomonas reinhardtii.

Although the circadian clock is a self-sustaining oscillator having a periodicity of nearly 1 d, its period length is not necessarily 24 h. Therefore, daily adjustment of the clock (i.e., resetting) is an essential mechanism for the circadian clock to adapt to daily environmental changes. One of the major cues for this resetting mechanism is light. In the unicellular green alga Chlamydomonas reinhardtii, the circadian clock is reset by blue/green and red light. However, the underlying molecular mechanisms remain largely unknown. In this study, using clock protein-luciferase fusion reporters, we found that the level of RHYTHM OF CHLOROPLAST 15 (ROC15), a clock component in C. reinhardtii, decreased rapidly after light exposure in a circadian-phase-independent manner. Blue, green, and red light were able to induce this process, with red light being the most effective among them. Expression analyses and inhibitor experiments suggested that this process was regulated mainly by a proteasome-dependent protein degradation pathway. In addition, we found that the other clock gene, ROC114, encoding an F-box protein, was involved in this process. Furthermore, we demonstrated that a roc15 mutant showed defects in the phase-resetting of the circadian clock by light. Taken together, these data strongly suggest that the light-induced degradation of ROC15 protein is one of the triggers for resetting the circadian clock in C. reinhardtii. Our data provide not only a basis for understanding the molecular mechanisms of light-induced phase-resetting in C. reinhardtii, but also insights into the phase-resetting mechanisms of circadian clocks in plants.

Differences in peri-hip articular pain after total hip arthroplasty between taper wedge stem and fit-and-fill stem.

Background: Total hip arthroplasty (THA) for hip disorders helps to alleviate pain and improve active daily life. When determining the effects of medical therapy and the subsequent clinical results, patient quality of life (QOL) also needs to be assessed. Recently, patient-reported outcomes (PRO) have become important as evaluation criteria. This study aimed to evaluate patient QOL and various PRO between different types of cementless stems and to clarify the relationship between PRO and stem-cortical bone contact. Methods: The study comprised 138 consecutive patients undergoing cementless THA for hip osteoarthritis. We assessed three different types of PRO: the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), patient's joint perception, and peri-hip articular joint pain (PHAP). We measured the state of contact between femur and implant by density mapping. Results: No significant difference was noted in PRO between stem types based on the JHEQ and patient's joint perception. PHAP occurred more frequently in the patients with a taper wedge stem versus a fit-and-fill stem. In both groups, distal contact was associated with PHAP but not with JHEQ results and patient's joint perception. Conclusion: The difference in PHAP between the two stem types groups was significant, with postoperative PHAP being higher with the taper wedge stem because of the more distal contact between the taper wedge stem and femur cortical bone.

Phase 1b study on the repurposing of meclizine hydrochloride for children with achondroplasia.

Achondroplasia (ACH) is a common skeletal dysplasia characterized by a disproportionately short stature. We found that meclizine, which is an over-the-counter drug for motion sickness, inhibited the fibroblast growth factor receptor 3 (FGFR3) gene using a drug repositioning strategy, and meclizine 1 and 2 mg/kg/day promoted bone growth in a mouse model of ACH. A previous phase 1a clinical trial for children with ACH demonstrated that a single dose of meclizine 25 and 50 mg was safe and that the simulated plasma concentration achieved steady state approximately 10 days after the first dose. The current study aimed to evaluate the safety and pharmacokinetics (PK) of meclizine in children with ACH after a 14-day-repeated dose of meclizine. Twelve patients with ACH aged 5-10 years were enrolled. Meclizine 12.5 (cohort 1) and 25 mg/day (cohort 2) were administered after meals for 14 days, and adverse events (AEs) and PK were evaluated. No patient experienced serious AEs in either group. The average (95% confidential interval [CI]) maximum drug concentration (Cmax), peak drug concentration (Tmax), area under the curve (AUC) from 0 to 24 h, and terminal elimination half-life (t1/2) after a 14-day-repeated administration of meclizine (12.5 mg) were 167 (83-250) ng/mL, 3.7 (3.1-4.2) h, 1170 (765-1570) ng·h/mL, and 7.4 (6.7-8.0) h, respectively. The AUC0-6h after the final administration was 1.5 times that after the initial dose. Cmax and AUC were higher in cohort 2 than in cohort 1 in a dose-dependent manner. Regarding the regimen of meclizine 12.5 and 25 mg in patients < 20 kg and ≥ 20 kg, respectively, the average (95% CI) AUC0-24h was 1270 (1100-1440) ng·h/mL. Compartment models demonstrated that the plasma concentration of meclizine achieved at a steady state after the 14th administration. Long-term administration of meclizine 12.5 or 25 mg/day is recommended for phase 2 clinical trials in children with ACH.

DNA methylation is associated with muscle loss in community-dwelling older men -the Yakumo study- : a preliminary experimental study.

Frailty is a state of reduced muscle strength and activity in older people. DNA methylation is associated with osteoporosis and muscle loss in murine and other animal studies, but there are no epidemiological studies in humans. This study aimed to assess the association of osteoporosis and muscle loss with DNA methylation in community-dwelling older people. This cross-sectional study was performed in a rural part of Japan. We analyzed 204 subjects (98 men and 106 women). In univariate analysis, the two groups were compared according to the presence or absence of osteoporosis and of muscle loss. Logistic regression analysis was performed to determine predictors of frailty in the muscle loss group. We used age, sex, body mass index, smoking history, drinking history, serum albumin and C-reactive protein levels, diabetes, hypertension, hyperlipidemia, heart disease history, and LINE-1 DNA methylation as the factors. Probability values < 0.05 were considered to be statistically significant. The levels of LINE-1 DNA methylation in leukocytes were associated with muscle loss in men over the age of 60. LINE-1 DNA methylation levels were not associated with bone mineral density in either the men or women over the age of 60. LINE-1 DNA methylation levels in leukocytes correlated significantly with the risk of frailty in men over the age of 60. Promoting an understanding of DNA methylation may lead to a better understanding of the pathophysiology of muscle loss.