Therapeutic effect of knee extension exercise with single-joint hybrid assistive limb following total knee arthroplasty: a prospective, randomized controlled trial.

The single-joint hybrid assistive limb (HAL-SJ), an exoskeletal robotic suit, offers functional improvement. In this prospective randomized controlled trial, we investigated the therapeutic effects of knee extension exercises using the HAL-SJ after total knee arthroplasty (TKA). Seventy-six patients with knee osteoarthritis were randomly assigned to HAL-SJ or conventional physical therapy (CPT) groups. The HAL-SJ group underwent exercise using the HAL-SJ for 10 days postoperatively, in addition to CPT; the CPT group underwent only CPT. Pain intensity and active and passive knee extension angles were evaluated preoperatively and on postoperative days 1-10 and weeks 2 and 4. Performance tests and Knee Injury and Osteoarthritis Outcome Scores (KOOS) were evaluated preoperatively and at postoperative weeks 2 and 4. Statistical analysis showed that the HAL-SJ group significantly improved active and passive knee extension angles compared with the CPT group. The HAL-SJ group showed immediate improvement in active knee extension angle through day 5. There were no significant differences in results between the performance tests and KOOS. Knee extension exercises with the HAL-SJ improved knee pain and the angle of extension in the acute phase after TKA.

Central Sensitization and Postoperative Improvement of Quality of Life in Total Knee and Total Hip Arthroplasty: A Prospective Observational Study.

Background: While total knee arthroplasty (TKA) and total hip arthroplasty (THA) lead to excellent clinical outcomes, some patients experience residual surgical site pain and reduced satisfaction. This prospective observational study investigated the prevalence of preoperative and postoperative residual central sensitization (CS) after TKA and THA. The influence of residual CS on the improvement in quality of life (QOL) was also investigated. Methods: The participants were 40 patients who underwent TKA and 47 patients who underwent THA. CS was measured using the central sensitization inventory (CSI) questionnaire. Knee symptoms were evaluated using the Knee Injury and Osteoarthritis Outcome Scales (KOOS), and hip symptoms were evaluated using the Japanese Orthopedic Association Hip-disease Evaluation Questionnaires (JHEQ). General QOL was evaluated using EuroQOL (EQ-5D-5l). Regression analysis was performed to estimate factors related to low QOL after surgery. Results: Preoperatively, 47.5% of TKA patients and 66.0% of THA patients were CS positive (P=0.083), which reduced to 10.0% (P=0.042) and 25.5% (P=0.202), respectively, 3 months after surgery. Although the improvements in KOOS subscales and EQ-5D-5l scores in TKA patients with residual CS were significantly lower than in those without residual CS, residual CS status had no effect on JHEQ subscales and EQ-5D-5l scores in THA patients. Regression analysis indicated that EQ-5D-5l was negatively correlated with CSI in the TKA group (P=0.017). In contrast, CSI was not correlated with EQ-5D-5l in the THA group (P=0.206). Conclusion: Postoperative QOL improvement was achieved 3 months after THA regardless of residual CS status. In contrast, preoperative CS was negatively associated with the improvement in QOL after TKA.

Influence of an antidiabetic drug on biomechanical and histological parameters around implants in type 2 diabetic rats.

OBJECTIVES: Type 2 diabetes mellitus (DM) has a deleterious effect on dental implant integration into alveolar bone, thought to arise from impaired osteoblast function and consequent reduced bone turnover. However, whether controlling blood glucose with antidiabetic drugs is sufficient to improve implant integration is unclear. This study was designed to evaluate implant integration using diabetic rats with/without an antidiabetic drug. MATERIALS AND METHODS: Titanium screws were surgically implanted in each tibia of 20 Goto-Kakizaki (GK) rats and 5 nondiabetic control rats. After 3 or 9 weeks, osseointegration was determined by testing the removal torque required to displace the screw and by histological analysis of various parameters of bone formation. RESULTS: Removal torque was significantly higher in the nondiabetic control group than in GK rats, irrespective of whether the GK rats had received voglibose. Histology revealed that single-labeled surface area was still high in the GK rats at 9 weeks but had peaked and diminished in control rats. Bone-implant contact area was reduced in GK rats. CONCLUSIONS: Despite controlling blood glucose, voglibose was unable to reverse the bone metabolic effects of DM.

Osteoblast differentiation is functionally associated with decreased AMP kinase activity.

Osteoblasts, originating from mesenchymal stem cells, play a pivotal role in bone formation and mineralization. Several transcription factors including runt-related transcription factor 2 (Runx2) have been reported to be essential for osteoblast differentiation, whereas the cytoplasmic signal transduction pathways controlling the differentiation process have not been fully elucidated. AMP-activated protein kinase (AMPK) is a serine-threonine kinase generally regarded as a key regulator of cellular energy homeostasis, polarity, and division. Recent lines of evidence have indicated that the activity of the catalytic alpha subunit of AMPK is regulated through its phosphorylation by upstream AMPK kinases (AMPKKs) including LKB1. Here, we explored the role of AMPK in osteoblast differentiation using in vitro culture models. Phosphorylation of AMPKalpha was significantly decreased during osteoblastic differentiation in both primary osteoblasts and MC3T3-E1, a mouse osteoblastic cell line. Conversely, the terminal differentiation of primary osteoblasts and MC3T3-E1 cells, represented by matrix mineralization, was significantly inhibited by glucose restriction and stimulation with metformin, both of which are known activators of AMPK. Matrix mineralization of MC3T3-E1 cells was also inhibited by the forced expression of a constitutively active form of AMPKalpha. Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn). Thus, our present data indicate that differentiation of osteoblasts is functionally associated with decreased AMPK activity.

ICH Q7A; 4.40 containment of beta-lactam antibiotics: an industry perspective.

The ICH Q7A guidance was finalized at the Fifth International Conference on Harmonization in San Diego, Nov. 9-11, 2000, and has been implemented in Japan since Nov. 2, 2001. However, in ICH Q7A; 4.40, Containment, there is no clear stipulation about whether a dedicated or multi-purpose facility should be employed in the production of highly sensitizing materials of different types of beta-lactam antibiotics, such as cephalosporins and cephems. This study presents the threshold levels for the induction of anaphylaxis by beta-lactam antibiotics to show that it is possible to use a multi-purpose facility for the production of several different types of beta-lactam antibiotics except for penicillins, if there are validated cleaning standards based on threshold values.