Validity and reliability of ankle morphological measurements on computerized tomography-synthesized planar radiographs.

BACKGROUND: Clinical success of total ankle arthroplasty depends heavily on the available information on the morphology of the bones, often obtained from measurements on planar radiographs. The current study aimed to evaluate the intra-rater, inter-rater and inter-session reliability and the validity of radiograph-based measurements of ankle morphology, and to quantify the effects of examiner experience on these measurements. METHODS: Twenty-four fresh frozen ankle specimens were CT scanned, data of which were used to reconstruct 3D volumetric bone models for synthesizing 2D radiographs. Two orthopaedic surgeons with different levels of clinical experience identified twenty landmarks five times on each of the synthesized sagittal and coronal radiographs and repeated the test on a subsequent day within 5 days. The landmarks were used to calculate fourteen morphological parameters. The two-way mixed-effects (ICC3,1), two-way random-effects (ICC2,k) and two-way random-effects (ICC3,k) models were used, respectively, to assess the intra-rater, inter-rater and inter-session reliability of measurements. The validity of the measurements for each examiner was assessed by comparing them with gold standard values obtained from the 2D radiographs projected from the 3D volumetric models using Pearson's correlation analysis and Bland and Altman plots, and the differences were defined as the measurement errors. RESULTS: Most of the morphological parameters were of good to very good intra-rater, inter-session and inter-rater reliability for both examiners (ICC > 0.61). Experience appeared to affect the inter-rater and inter-session reliability, the senior examiner showing greater inter-session ICC values than the junior examiner. Most of the tibial parameters had moderate to excellent correlations with the corresponding gold standard values but were underestimated by both examiners, in contrast to most of the talar parameters that were overestimated and had only poor to fair correlations. CONCLUSIONS: Most of the morphological parameters of the ankle can be estimated from radiographs with good to very good intra-rater, inter-session and inter-rater reliability, for both clinically experienced and less experienced examiners. Clinical experience helped increase the reliability of repeated evaluations after a longer interval, such as in a follow-up assessment. It is suggested that critical clinical decisions based on repeated morphology measurements should be made by more experienced surgeons or after appropriate training.

Evaluation of three force-position hybrid control methods for a robot-based biological joint-testing system.

BACKGROUND: Robot-based joint-testing systems (RJTS) can be used to perform unconstrained laxity tests, measuring the stiffness of a degree of freedom (DOF) of the joint at a fixed flexion angle while allowing the other DOFs unconstrained movement. Previous studies using the force-position hybrid (FPH) control method proposed by Fujie et al. (J Biomech Eng 115(3):211-7, 1993) focused on anterior/posterior tests. Its convergence and applicability on other clinically relevant DOFs such as valgus/varus have not been demonstrated. The current s1tudy aimed to develop a 6-DOF RJTS using an industrial robot, to propose two new force-position hybrid control methods, and to evaluate the performance of the methods and FPH in controlling the RJTS for anterior/posterior and valgus/varus laxity tests of the knee joint. METHODS: An RJTS was developed using an industrial 6-DOF robot with a 6-component load-cell attached at the effector. The performances of FPH and two new control methods, namely force-position alternate control (FPA) and force-position hybrid control with force-moment control (FPHFM), for unconstrained anterior/posterior and valgus/varus laxity tests were evaluated and compared with traditional constrained tests (CT) in terms of the number of control iterations, total time and the constraining forces and moments. RESULTS: As opposed to CT, the other three control methods successfully reduced the constraining forces and moments for both anterior/posterior and valgus/varus tests, FPHFM being the best followed in order by FPA and FPH. FPHFM had root-mean-squared constraining forces and moments of less than 2.2 N and 0.09 Nm, respectively at 0° flexion, and 2.3 N and 0.14 Nm at 30° flexion. The corresponding values for FPH were 8.5 N and 0.33 Nm, and 11.5 N and 0.45 Nm, respectively. Given the same control parameters including the compliance matrix, FPHFM and FPA reduced the constraining loads of FPH at the expense of additional control iterations, and thus increased total time, FPA taking about 10 % longer than FPHFM. CONCLUSIONS: The FPHFM would be the best choice among the methods considered when longer total time is acceptable in the intended clinical applications. The current results will be useful for selecting a force-position hybrid control method for unconstrained laxity tests using an RJTS.

Three-dimensional computer graphics-based ankle morphometry with computerized tomography for total ankle replacement design and positioning.

Morphometry of the bones of the ankle joint is important for the design of joint replacements and their surgical implantations. However, very little three-dimensional (3D) data are available and not a single study has addressed the Chinese population. Fifty-eight fresh frozen Chinese cadaveric ankle specimens, 26 females, and 32 males, were CT-scanned in the neutral position and their 3D computer graphics-based models were reconstructed. The 3D morphology of the distal tibia/fibula segment and the full talus was analyzed by measuring 31 parameters, defining the relevant dimensions, areas, and volumes from the models. The measurements were compared statistically between sexes and with previously reported data from Caucasian subjects. The results showed that, within a general similarity of ankle morphology between the current Chinese and previous Caucasian subjects groups, there were significant differences in 9 out of the 31 parameters analyzed. From a quantitative comparison with available prostheses designed for the Caucasian population, few of these designs have both tibial and talar components suitable in dimension for the Chinese population. The current data will be helpful for the sizing, design, and surgical positioning of ankle replacements and for surgical instruments, especially for the Chinese population.

Inter-joint sharing of total support moments in the lower extremities during gait in narrow-heeled shoes of different heights.

The study aimed to investigate the influence of the base and height of shoe heels on the total support moment (Ms) and individual joint contributions during gait. Fifteen healthy females walked barefoot and with narrow-heeled shoes (heel heights: 3.9, 6.3 and 7.3 cm) while kinematic and kinetic data were measured. Compared with the barefoot condition, the subjects maintained unaltered Ms in the sagittal plane in shod conditions. This was achieved by increasing the knee extensor moment to compensate for the diminished ankle plantarflexor moments in medium and high heel conditions. In the frontal plane, subjects in shod conditions had to sustain an increased Ms for balance control during late single-leg stance with increased knee abductor and ankle pronator moments as a result of the reduced base of the heels. The results will be helpful for future shoe designs to reduce fall risks and prevent relevant musculoskeletal problems.

Comparison of the Radiographic and Clinical Outcomes between the Sinus Tarsi and Extended Lateral Approaches for Intra-Articular Calcaneal Fractures: A Retrospective Study.

The aim of this study was to compare the radiological and functional outcomes of the extended lateral and sinus tarsi approaches for managing displaced intraarticular calcaneal fractures. This retrospective study involved 44 patients with displaced intra-articular calcaneal fractures. The patients were treated with either the extended lateral or sinus tarsi approach and followed up for at least a year. The radiological and clinical outcomes were compared between the approaches. The waiting time for surgery was shorter and the complication rate was lower in the sinus tarsi approach group than in the other group. There were no significant differences in the American Orthopedic Foot and Ankle Society ankle-hindfoot score, Foot Function Index, or visual analog scale score between the groups. In both groups, the radiological outcomes (Böhler angle, calcaneal width, and calcaneal height) were better postoperatively than preoperatively. The sinus tarsi approach is a safe and effective alternative to the extended lateral approach for managing displaced intraarticular calcaneal fractures. It is associated with a lower complication rate and a shorter waiting time for surgery than the extended lateral approach, with similar functional and radiological outcomes.

Impact of Vitamin D Receptor Genotypes on Taiwan Hallux Valgus.

BACKGROUND/AIM: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV. MATERIALS AND METHODS: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk. RESULTS: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively). CONCLUSION: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV.

Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.

BACKGROUND/AIM: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL. MATERIALS AND METHODS: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair. RESULTS: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele. CONCLUSION: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.

Effects of positioning on radiographic measurements of ankle morphology: a computerized tomography-based simulation study.

BACKGROUND: Measurements of the morphology of the ankle joint, performed mostly for surgical planning of total ankle arthroplasty and for collecting data for total ankle prosthesis design, are often made on planar radiographs, and therefore can be very sensitive to the positioning of the joint during imaging. The current study aimed to compare ankle morphological measurements using CT-generated 2D images with gold standard values obtained from 3D CT data; to determine the sensitivity of the 2D measurements to mal-positioning of the ankle during imaging; and to quantify the repeatability of the 2D measurements under simulated positioning conditions involving random errors. METHOD: Fifty-eight cadaveric ankles fixed in the neutral joint position (standard pose) were CT scanned, and the data were used to simulate lateral and frontal radiographs under various positioning conditions using digitally reconstructed radiographs (DRR). RESULTS AND DISCUSSION: In the standard pose for imaging, most ankle morphometric parameters measured using 2D images were highly correlated (R > 0.8) to the gold standard values defined by the 3D CT data. For measurements made on the lateral views, the only parameters sensitive to rotational pose errors were longitudinal distances between the most anterior and the most posterior points of the tibial mortise and the tibial profile, which have important implications for determining the optimal cutting level of the bone during arthroplasty. Measurements of the trochlea tali width on the frontal views underestimated the standard values by up to 31.2%, with only a moderate reliability, suggesting that pre-surgical evaluations based on the trochlea tali width should be made with caution in order to avoid inappropriate selection of prosthesis sizes. CONCLUSIONS: While highly correlated with 3D morphological measurements, some 2D measurements were affected by the bone poses in space during imaging, which may affect surgical decision-making in total ankle arthroplasty, including the amount of bone resection and the selection of the implant sizes. The linear regression equations for the relationship between 2D and 3D measurements will be helpful for correcting the errors in 2D morphometric measurements for clinical applications.

Interleukin-8 Rs4073 Genotypes as Prognostic Predictors for Childhood Acute Lymphocytic Leukemia.

BACKGROUND/AIM: Interleukin 8 (IL-8) is highly expressed in refractory acute lymphocytic leukemia (ALL) cells. This study aimed to investigate the contribution of IL-8 polymorphisms to the risk of childhood ALL. MATERIALS AND METHODS: The genotypes of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were determined in 266 childhood ALL cases and 266 controls using the PCR-RFLP method. Additionally, we assessed whether the interactions of these genotypes with age and sex contributed to childhood ALL risk. RESULTS: The distributions of genotypic and allelic frequencies of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were not significantly different between childhood ALL cases and controls (all p>0.05). However, carriers of the variant AA genotype at IL-8 rs4073 had a significantly higher risk of childhood ALL among those aged ≤3.5 years and among girls (OR=2.39 and 3.32, 95%CI=1.21-4.73 and 1.51-7.30, p=0.0182 and 0.0042, respectively). In the stratification analysis, IL-8 rs4073 AT and AA genotypes were associated with higher childhood ALL risk classification and shorter survival time (OR=2.21 and 4.13, 95%CI=1.29-3.78 and 1.87-9.10, p=0.0054 and 0.0002, respectively). There was no positive association for rs2227306, rs2227543, or rs1126647 (all p>0.05). CONCLUSION: The A allele of IL-8 rs4073 can serve as a diagnostic predictor for childhood ALL, but only in girls and patients younger than or equal to 3.5 years old. More importantly, it can serve as a prognostic marker for high-risk classification and shorter survival time. Further validation studies can help extend the use of this prognostic predictor in clinical practice.

Effects of lateral instability on ankle coupled motions in vivo using 3D fluoroscopy.

Lateral ankle instability (LAI) compromises the normal kinematics of the ankle, affecting activities of daily living. In vitro kinematics of ankles with LAI during single-plane motions are available, but the active control stability of these motions remains unclear. The current study measured the 3D ankle kinematics during unresisted single-plane motion tests using a bi-plane fluoroscope with a CT model-based 2D/3D registration method in 12 patients with LAI and 14 healthy peers. The coupling of the kinematic components at the talocrural and subtalar joints was quantified by the path difference between the forward and return paths of the coupled motion. Significantly increased path differences were found in the subtalar dorsiflexion/plantarflexion and inversion/eversion components during internal/external rotation tests (p < 0.05). During inversion/eversion, significantly reduced tibiocalcaneal ranges of motion and the path differences in the talocrural and subtalar dorsiflexion/plantarflexion components were noted (p < 0.05). The current results suggest that chronic LAI had compromised control stability at the subtalar joint during internal/external rotation tests and a conservative motion control strategy with significantly reduced ranges of motion to maintain good control of out-of-plane motion components in response to direct challenges of the anterior talofibular ligament during inversion/eversion tests. The current results also suggest that, compared to kinematic patterns of individual components, the path difference of the coupled motion may serve as a better measure of the motion control stability of the ankle in differentiating LAI from healthy controls.

CCN3 increases BMP-4 expression and bone mineralization in osteoblasts.

The nephroblastoma overexpressed (NOV) gene, also called CCN3, regulates differentiation of skeletal mesenchymal cells. Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and bone formation, but the effects of CCN3 on BMP expression and bone formation in cultured osteoblasts are largely unknown. Here we found that CCN3 increased BMP-4 expression and bone nodule formation in cultured osteoblast. Monoclonal antibodies for α5ß1 and αvß5 integrins, and inhibitors of integrin-linked kinase (ILK), p38, and JNK, all inhibited CCN3-induced bone nodule formation and BMP-4 up-regulation of osteoblasts. CCN3 stimulation increased the kinase activity of ILK and phosphorylation of p38 and JNK. Inhibitors of activator protein-1 (AP-1) also suppressed bone nodule formation and BMP-4 expression enhanced by CCN3. Moreover, CCN3-induced c-Jun translocation into the nucleus, and the binding of c-Jun to the AP-1 element on the BMP-4 promoter were both inhibited by specific inhibitors of the ILK, p38, and JNK cascades. Taken together, our results provide evidence that CCN3 enhances BMP-4 expression and bone nodule formation in osteoblasts, and that the integrin receptor, ILK, p38, JNK, and AP-1 signaling pathways may be involved.

Synergistic multi-joint kinematic strategies to reduce tripping risks during obstacle-crossing in older long-term Tai-Chi Chuan practitioners.

Introduction: Losing balance or tripping over obstacles is considered one of the most common causes of falls in the elderly. Tai-Chi Chuan (TCC) has been shown to improve muscle strength, inter-joint coordination and balance control in the elderly. This study aimed to determine whether older long-term TCC practitioners would show multi-joint kinematic strategies that would reduce the risk of tripping during obstacle-crossing compared to peers without TCC experience. Methods: Three-dimensional motions of the pelvis and lower extremities were measured using a motion capture system in fifteen older long-term TCC practitioners (TCC group) and 15 healthy controls without TCC experience during walking and crossing obstacles of three different heights. Crossing angles of the pelvis and lower limbs and toe-obstacle clearances were obtained and analyzed using two-way analyses of variance to study the between-subject (group) and within-subject (height) effects. A multi-link system approach was used to reveal the relationship between joint angular changes and toe-obstacle clearances. Results: Compared to the controls, the TCC group showed increased leading and trailing toe-obstacle clearances (p < 0.05) with increased pelvic hiking and hip flexion but decreased hip adduction on the swing side and decreased knee flexion on the stance side during leading-limb crossing (p < 0.05), and increased pelvic hiking and anterior tilt but decreased hip adduction on the swing side, and decreased knee flexion on the stance side during trailing limb crossing (p < 0.05). All significant joint angular changes contributed to the increases in the toe-obstacle clearances. Conclusion: The current study identified the kinematic changes of the pelvis and the lower limb joints and revealed a specific synergistic multi-joint kinematic strategy to reduce tripping risks during obstacle-crossing in older long-term TCC practitioners as compared to non-TCC controls. The observed multi-joint kinematic strategies and the associated increases in toe-obstacle clearances appeared to be related to the training characteristics of TCC movements. Long-term TCC practice may be helpful for older people in reducing the risk of tripping and the subsequent loss of balance.

Effects of long-term Tai-Chi Chuan practice on whole-body balance control during obstacle-crossing in the elderly.

Older people are subject to an increased risk of falling compared to the young, especially during obstacle negotiation. This study aimed to quantify the effects of long-term Tai-Chi Chuan (TCC) practice on the balance control during obstacle-crossing in older people in terms of the inclination angles (IA) of the body's centre of mass (COM) relative to the centre of pressure (COP), and the rate of change of IA (RCIA). Fifteen healthy older adults who had practised TCC for at least 13 years and 15 healthy controls without any experience in TCC performed obstacle-crossing in a gait laboratory. The TCC group showed significantly greater leading and trailing toe-obstacle clearances but smaller trailing stride lengths when compared to controls. In the sagittal plane, the TCC group showed significantly smaller average anterior IA when the COM was anterior to the COP but greater average posterior IA when the COM was posterior to the COP, with significantly smaller average and peak RCIA over the crossing cycle. Long-term TCC practitioners showed an obstacle-crossing technique for less risk of tripping and better balance control, as indicated respectively by significantly increased toe-obstacle clearances and more posterior COM position relative to the COP with smaller anterior IA and RCIA during leading crossing and greater posterior IA and frontal RCIA at trailing-toe crossing. These benefits appeared to be related to the main features of TCC movements that emphasized maintaining balance during single-leg support and keeping the body weight on the trailing limb during the slow weight-shifting of double-limb support.

Makoplasty medial unicondylar knee replacement: Correction or postoperative angle matters?

INTRODUCTION: Various considerations prevail around optimal postoperative varus deformity, correction angle and physiological constitutional varus deformity. The goal of our present study was to understand correlation between these parameters and their influence over Western Ontario McMaster University Osteoarthritis Index scale (WOMAC). MATERIALS AND METHODS: Consecutive robotic-arm-assisted medial onlay fixed bearing unicompartmental knee arthroplasty (UKA) in 143 knees studied. WOMAC score was recorded preoperatively and at specific intervals after surgery for consecutive 2 years. RESULTS: Mean preoperative and postoperative varus deformities were 10.2° and 4.8°, respectively, and mean correction angle was 5.4°. The preoperative varus and correction angles were found well correlated (r = 0.815). The amount of improvement in the WOMAC total score was not influenced by the postoperative varus angle. CONCLUSION: The correction angle has a stronger correlation with preoperative varus deformity, and postoperative varus deformity does not imply favourable clinical outcomes.

Resection with limb salvage in an Asian male adolescent with Ewing's sarcoma: A case report.

BACKGROUND: Ewing's sarcoma is a highly malignant primary bone tumor that commonly affects children. For young patients, multidisciplinary treatment and limb salvage are recommended, and surgical plans considering the growth potential and bone activity after tumor resection are essential. CASE SUMMARY: An 11-year-old Asian boy had a 1-mo history of a right-sided limping gait. Imaging revealed a proximal tumor with bone destruction and physeal involvement over the right femoral neck. He was diagnosed with stage IV (T1N0M1aG3) Ewing's sarcoma with bilateral lung metastases. Neoadjuvant chemotherapy decreased the tumor size and confined it to the metaphyseal region. The patient underwent four stages of surgery: wide tumor excision plus reconstruction with vascular fibular bone graft plus internal fixation; repeat open reduction and internal fixation; femoral lengthening with orthosis after physeal maturity; and orthosis removal and bone elongation (approximately 6 cm). Following surgery, he could walk without discomfort and had almost equal-sized bilateral femoral heads, indicating physis preservation. The surgery was successful, and normal femoral head growth was achieved after complete remission. The patient was able to resume normal activities with equal length of the bilateral lower limbs. CONCLUSION: Tumor treatment and reconstruction following resection are important in skeletally immature patients with Ewing's sarcoma to improve quality of life.

Bacillus Calmette-Guérin (BCG) osteomyelitis among children: Experience in a single tertiary center in central Taiwan.

BACKGROUND: The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on. METHODS: This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis. RESULTS: In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively). CONCLUSION: BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome.

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.

BACKGROUND/AIM: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). CONCLUSION: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.

CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway.

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN3, also called nephroblastoma overexpressed gene (NOV), regulates proliferation and differentiation of cancer cells. However, the effect of CCN3 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). αvß3 or αvß5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase (PI3K) inhibitors (Ly294002 and wortmannin) and Akt inhibitor inhibited the CCN3-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. CCN3 stimulation increased the phosphorylation of focal adhesion kinase (FAK), PI3K, and Akt. In addition, NF-κB inhibitors also suppressed the cell migration and MMP-13 expression enhanced by CCN3. Moreover, CCN3 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-13 promoter. Taken together, our results indicate that CCN3 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the αvß3/αvß5 integrin receptor, FAK, PI3K, Akt, p65, and NF-κB signal transduction pathway.

Best-Compromise Control Strategy Between Mechanical Energy Expenditure and Foot Clearance for Obstacle-Crossing in Older Adults: Effects of Tai-Chi Chuan Practice.

Background: Obstacle-crossing increases the risk of falls in older people. This study aimed to identify the effects of long-term Tai-Chi Chuan (TCC) practice on the control strategies for obstacle-crossing in older people. Methods: A multi-objective optimal control technique with measured gait data was used to identify the control strategies adopted by 15 long-term TCC practitioners and 15 healthy controls when crossing obstacles of different heights, in terms of the best-compromise weighting sets for the conflicting objectives of minimizing energy expenditure and maximizing the toe-obstacle and heel-obstacle clearances. Results and Conclusions: The long-term TCC older practitioners adopted a best-compromise control strategy similar to those adopted by young adults, with greater weightings on the minimization of the mechanical energy expenditure and smaller weightings on foot-clearance as compared to non-TCC controls (TCC: 0.72, 0.14, 0.14; Control: 0.55, 0.225, 0.225). This strategy enabled the long-term TCC older practitioners to cross obstacles with significantly greater leading-toe clearances but with relatively less mechanical energy expenditure. With the current approach, further simulations of obstacle-crossing mechanics with a given weighting set will be useful for answering clinically relevant what-if questions, such as what abilities would be needed if the non-TCC older people were to cross obstacles using the crossing strategy of the TCC people.