Virtual reality skateboarding training for balance and functional performance in degenerative lumbar spine disease.

BACKGROUND: Degenerative lumbar spine disease (DLD) is a prevalent condition in middle-aged and elderly individuals. DLD frequently results in pain, muscle weakness, and motor impairment, which affect postural stability and functional performance in daily activities. Simulated skateboarding training could enable patients with DLD to engage in exercise with less pain and focus on single-leg weight-bearing. The purpose of this study was to investigate the effects of virtual reality (VR) skateboarding training on balance and functional performance in patients with DLD. METHODS: Fourteen patients with DLD and 21 age-matched healthy individuals completed a 6-week program of VR skateboarding training. The motion capture and force platform systems were synchronized to collect data during a single-leg stance test (SLST). Musculoskeletal simulation was utilized to calculate muscle force based on the data. Four functional performance tests were conducted to evaluate the improvement after the training. A Visual Analogue Scale (VAS) was also employed for pain assessment. RESULTS: After the training, pain intensity significantly decreased in patients with DLD (p = 0.024). Before the training, patients with DLD took longer than healthy individuals on the five times sit-to-stand test (p = 0.024). After the training, no significant between-group differences were observed in any of the functional performance tests (p > 0.05). In balance, patients with DLD were similar to healthy individuals after the training, except that the mean frequency (p = 0.014) was higher. Patients with DLD initially had higher biceps femoris force demands (p = 0.028) but shifted to increased gluteus maximus demand after the training (p = 0.037). Gluteus medius strength significantly improved in patients with DLD (p = 0.039), while healthy individuals showed consistent muscle force (p > 0.05). CONCLUSION: This is the first study to apply the novel VR skateboarding training to patients with DLD. VR skateboarding training enabled patients with DLD to achieve the training effects in a posture that relieves lumbar spine pressure. The results also emphasized the significant benefits to patients with DLD, such as reduced pain, enhanced balance, and improved muscle performance.

Dynamic changes in transcriptome during orthodontic tooth movement.

OBJECTIVES: The objective of this study was to determine global changes in gene expression with next generation sequencing (NGS) in order to assess the biological effects of orthodontic tooth movement (OTM) on alveolar bone in a rat model. MATERIALS AND METHODS: Thirty-five Wistar rats (age 14 weeks) were used in the study. The OTM was performed using closed coil Nickel-Titanium spring to apply a mesial force on maxillary first molars of 8-10 g. Three hours, 1, 3, 7 and 14 days after the placement of the appliance, rats were killed at each time point respectively. The alveolar bone, around left maxillary first molar, were excised on compression side. The samples were immediately frozen in liquid nitrogen for subsequent RNA extraction. Total RNA samples were prepared for mRNA sequencing using the Illumina kit. RNA-Seq reads were aligned to the rat genomes using the STAR Aligner and bioinformatic analysis was performed. RESULTS: A total of 18 192 genes were determined. Day 1 has the highest number of differentially expressed genes (DEGs) observed with more upregulated than downregulated genes. A total of 2719 DEGs were identified to use as input for the algorithm. Six distinct clusters of temporal patterns were observed representing proteins that were differentially regulated indicating different expression kinetics. Principal component analysis (PCA) showed distinct clustering by time points and days 3, 7 and 14 share similar gene expression pattern. CONCLUSIONS: Distinct gene expression pattern was observed at different time points studied. Hypoxia, inflammation and bone remodelling pathways are major mechanisms behind OTM.

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis.

BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification.

BACKGROUND: Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross-talk between EGFR and BMP2 signals in developing and adult growth plates. RESULTS: Using in vivo mouse models of conditional cartilage-targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR-deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2-deficient growth plates. EGFR-deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist. CONCLUSIONS: Cross-talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross-talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.

How does alendronate affect orthodontic tooth movement in osteogenesis imperfecta: an in vivo study on a mice model.

OBJECTIVES: The purpose of this study was to evaluate the effects of alendronate on orthodontic tooth movement (OTM) and bone modelling/remodelling in an osteogenesis imperfecta (OI) mice model. MATERIALS AND METHODS: Ten-week-old male and female OI mice (Col1a2oim, n = 32) were divided into four groups: 1. Alendronate male (AM, n = 8), 2. Alendronate female (AF, n = 8), 3. saline male (SM, n = 8), and 4. saline female (SF, n = 8). The mice in all four groups received either Alendronate (0.05 mg/kg) or vehicle (saline 0.05 mg/kg) subcutaneously for 2 weeks prior to the placement of orthodontic spring. A nickel-titanium spring applying 3-5 cN of force was used to perform the OTM for 1 week. After 7 days of OTM, the OI mice were euthanized with CO2 inhalation and microfocus computed tomography and histological analyses were performed. RESULTS: AM and AF mice showed a significant decrease (P < 0.05) in the rate of OTM compared with SM and SF mice, respectively. In addition, AM and AF mice showed a significant increase (P < 0.05) in the bone volume fraction (BVF) and tissue density (TD) compared with SM and SF mice. Histological analysis of haematoxylin-eosin staining revealed a hyalinization zone in AM and AF mice compared with SM and SF mice. Furthermore, tartrate-resistant acid phosphatase staining indicated decreased number of osteoclasts in AM and AF mice compared with SM and SF mice. Picrosirius red staining showed, Alendronate treatment led to thick uniform and smooth morphology of collagen fibres as compared with saline group. Similarly, second harmony generation images also revealed thicker collagen fibres at the periodontal ligament (PDL)-cementum entheses and PDL-alveolar bone entheses in AM and AF mice compared with SM and SF mice. CONCLUSIONS: Alendronate led to a decrease in the rate of OTM, increase in BVF and TD, decrease in the number of osteoclasts, and smooth and thick collagen fibres compared with saline in both male and female OI mice.

Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in BRAFV600E-Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study.

Background and Objectives: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.

Comparison of Next-Generation Sequencing and Polymerase Chain Reaction for Personalized Treatment-Related Genomic Status in Patients with Metastatic Colorectal Cancer.

Personalized treatments based on the genetic profiles of tumors can simultaneously optimize efficacy and minimize toxicity, which is beneficial for improving patient outcomes. This study aimed to integrate gene alterations associated with predictive and prognostic outcomes in patients with metastatic colorectal cancer (mCRC) with polymerase chain reaction (PCR) and in-house next-generation sequencing (NGS) to detect KRAS, NRAS, and BRAF mutations. In the present study, 41 patients with mCRC were assessed between August 2017 and June 2019 at a single institution. The overall concordance between NGS and PCR results for detecting KRAS, NRAS, and BRAF mutations was considerably high (87.8-92.7%), with only 15 discrepant results between PCR and NGS. Our companion diagnostic test analyzes KRAS, NRAS, and BRAF as a panel of CRC molecular targets; therefore, it has the advantages of requiring fewer specimens and being more time and cost efficient than conventional testing for separate analyses, allowing for the simultaneous analysis of multiple genes.

Vitamin E enriched diet increases the rate of orthodontic tooth movement.

INTRODUCTION: Vitamin E is a popular antioxidant suggested to affect bone turnover. However, the effects of a vitamin E enriched diet on the rate of tooth movement are unknown. Therefore, this study aimed to evaluate tooth movement in rats receiving a vitamin E enriched diet. In addition, we examined bone remodeling in experimental and control rats. METHODS: Thirty-two 6-week-old male rats were divided into 4 groups: (1) group 1 (n = 8): orthodontic tooth movement (OTM) for 4 days + regular diet; (2) group 2 (n = 8): OTM for 14 days + regular diet; (3) group 3 (n = 8): OTM for 4 days + vitamin E diet; and (4) group 4 (n = 8) - OTM for 14 days + vitamin E diet. Maxillary alveolar bones and femurs of rats were analyzed by microcomputed tomography and histology. RESULTS: Rats fed a vitamin E diet presented an increased OTM rate at days 4 and 14. We found an increased number of osteoclasts and decreased bone volume in the vitamin E diet group at day 14 of OTM. In addition, there was increased expression of the microphthalmia-associated transcription factor in the alveolar bone of the vitamin E diet group. In contrast, there was no difference in bone remodeling in femurs or alveolar bone at the control side. CONCLUSIONS: We found that an enriched vitamin E diet increases the rate of OTM in rats, suggesting that vitamin E may be useful as an avenue to accelerate OTM.

Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer.

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF--5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal-epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.

The effect of differential force system and minimal surgical intervention on orthodontic tooth movement and root resorption.

OBJECTIVE: The primary objective of this study was to quantify the orthodontic tooth movement (OTM) and orthodontically induced root resorption (OIRR) with differential force system in conjunction with minimal surgical insult. MATERIAL AND METHODS: 15-week-old, 48 male Wistar rats were used in the research and were randomly divided into six groups: 1. Group 1 (8 Wistar rats): OTM for 14 days with 8-g force; 2. Group 2 (8 Wistar rats): OTM for 14 days with 25-g force; 3. Group 3 (8 Wistar rats): OTM for 14 days with 100-g force; 4. Group 4 (8 Wistar rats): OTM for 14 days with 8-g force and alveolar decortications (ADs); 5. Group 5 (8 Wistar rats): OTM for 14 days with 25-g force and ADs; 6. Group 6 (8 Wistar rats): OTM for 14 days with 100-g force and ADs. A nickel-titanium spring was used to protract the molar mesially using maxillary incisors as an anchorage. ADs (minimal surgical insult) were done using a hand piece and a round bur, adjacent to the left first maxillary molar on the palatal alveolar bone. After 14 days of OTM, Wistar rats were killed and microfocus computed tomography and histological analysis were performed. RESULTS: The 100-g group showed significant increase (P < 0.05) in OTM. However, with ADs, the OTM was significantly higher (P < 0.05) in 8 and 100 g. In addition, with ADs, there is significant increase (P < 0.05) in OIRR and significant decrease (P < 0.05) in bone volume fraction. Histological quantification of tartrate-resistant acid phosphatase indicated a significant increase (P < 0.05) in the number of osteoclasts with ADs when compared without ADs. CONCLUSIONS: Light force in conjunction with ADs are optimal to accelerate the OTM. Additionally, ADs increases the OIRR.

BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer-A Case Series Study Target Therapy of BRAF-Mutated mCRC.

Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1-26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1-2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.

Feasibility of robot-assisted surgery in elderly patients with rectal cancer.

BACKGROUND: Although surgical resection is the main treatment for rectal cancer, the optimal surgical protocol for elderly patients with rectal cancer remains controversial. This study evaluated the feasibility of robot-assisted surgery in elderly patients with rectal cancer. PATIENTS AND METHODS: This retrospective study enrolled 156 patients aged 28-93 years diagnosed with Stage I-III rectal cancer, who underwent robot-assisted surgery between May 2013 and December 2018 at a single institution. RESULTS: In total, 156 patients with rectal cancer, including 126 non-elderly (aged < 70 years) and 30 elderly (aged ≥70 years) patients, who underwent robot-assisted surgery were recruited. Between the patient groups, the post-operative length of hospital stay did not differ statistically significantly (P = 0.084). The incidence of overall post-operative complications was statistically significantly lower in the elderly group (P = 0.002). The disease-free and overall survival did not differ statistically significantly between the two groups (P = 0.719 and 0.390, respectively). CONCLUSIONS: Robot-assisted surgery for rectal cancer was well tolerated by elderly patients, with similar results to the non-elderly patients. Oncological outcomes and survival did not depend on patient age, suggesting that robot-assisted surgery is a feasible surgical modality for treating operable rectal cancer and leads to age-independent post-operative outcomes in elderly patients.

Impact of previous abdominal surgery on robotic-assisted rectal surgery in patients with locally advanced rectal adenocarcinoma: a propensity score matching study.

BACKGROUND: The application of minimally invasive surgery in patients with colorectal cancer (CRC) and a history of previous abdominal surgery (PAS) remains controversial. This retrospective study with propensity score matching (PSM) investigated the impact of PAS on robotic-assisted rectal surgery outcomes in patients with locally advanced rectal adenocarcinoma undergoing preoperative concurrent chemoradiotherapy (CCRT). METHODS: In total, 203 patients with locally advanced rectal adenocarcinoma who underwent preoperative CCRT and robotic-assisted rectal surgery between May 2013 and December 2019 were enrolled. Patients were categorized into PAS and non-PAS groups based on the PAS history. The PSM caliper matching method with 1-to-3 matches was used to match PAS patients with non-PAS. RESULTS: Of the 203 enrolled patients, 35 were PAS patients and 168 were non-PAS patients. After PSM, 32 PAS patients and 96 non-PAS patients were included for analysis. No significant between-group differences were noted in the perioperative outcomes, including median console time (165 min (PAS) vs. 175 min (non-PAS), P = 0.4542) and median operation time (275 min (PAS) vs. 290 min (non-PAS), P = 0.5943) after PSM. Postoperative recovery and overall complication rates were also similar (all P > 0.05). Moreover, the between-group differences in pathological or short-term oncological outcomes were also nonsignificant (all P > 0.05). No 30-day postoperative deaths were observed in either group. CONCLUSION: The current results indicate that robotic-assisted surgery is safe and feasible for PAS patients with locally advanced rectal adenocarcinoma undergoing preoperative CCRT. However, future prospective randomized clinical trials are required to verify these findings.

Raloxifene administration enhances retention in an orthodontic relapse model.

BACKGROUND AND OBJECTIVES: Orthodontic relapse is a physiologic process that involves remodelling of the alveolar bone and principle periodontal ligament fibres. Raloxifene is an Food and Drug Administration (FDA)-approved selective oestrogen receptor modulator that inhibits systemic bone loss. In our study, we examined the effects of Raloxifene on alveolar bone modelling and orthodontic relapse in a rodent model. MATERIALS AND METHODS: The efficacy of raloxifene was evaluated in 15-week-old male Wistar rats, 8 in each group (Control, Raloxifene, Raloxifene + 7-day relapse, Raloxifene + 14-day relapse) for a total of 42 days. All animals had 14 days of orthodontic tooth movement with a closed nickel-titanium coil spring tied from incisors to right first molar applying 5-8 gm of force. On the day of appliance removal, impression was taken with silicon material and the distance between first molar and second molar was filled with light-cured adhesive resin cement for retention phase. Raloxifene Retention, Raloxifene Retention + 7D, Raloxifene Retention + 14D groups received 14 daily doses of raloxifene (2.0 mg/kg/day) subcutaneously after orthodontic tooth movement during retention. After 14 days of retention, the retainer was removed and right first molar was allowed to relapse for a period of 14 days. Raloxifene injection continued for the Raloxifene + 14-day relapse group during relapse phase too. Control group received saline injections during retention. Animals were euthanized by CO2 inhalation. The outcome measure included percentage of relapse, bone volume fraction, tissue density, and histology analysis using tartrate-resistant acid phosphatase staining and determining receptor activator of nuclear factor-кB-ligand (RANKL) and osteoprotegerin expression. RESULTS: Raloxifene Retention + 14D group had significantly less (P < 0.05) orthodontic relapse when compared with other groups. There was a significant increase (P < 0.05) in bone volume fraction and tissue density in the Raloxifene Retention + 14D group when compared with other groups. Similarly, there was significant decrease in number of osteoclasts and RANKL expression in Raloxifene Retention + 14D group when compared with Raloxifene Retention + 7D group (P < 0.05). CONCLUSION: Raloxifene could decrease post-orthodontic treatment relapse by decreasing bone resorption and indirectly enhancing bone formation.

Injectable RANKL sustained release formulations to accelerate orthodontic tooth movement.

BACKGROUND: Accelerating orthodontic tooth movement (OTM) through biologically effective methods, such as increasing osteoclast-mediated alveolar resorption, could effectively shorten treatment time. OBJECTIVE: To evaluate an injectable formulation containing receptor activator of nuclear factor kappa-B ligand (RANKL) on the OTM. MATERIALS AND METHODS: We fabricated a RANKL formulation from 100 µl of 100 µg/ml RANKL adsorbed on 10 mg of poly(lactic acid-co-glycolic acid) microspheres embedded in a 10 wt% aqueous hydroxyethyl cellulose carrier gel. We characterized these formulations for the rate of RANKL release, and then tested for bioactivity using in vitro cell culture. In vivo OTM studies were conducted using 15 week old male Wistar rats for 14 days. We injected the RANKL formulations palatal to the left maxillary first molar and accomplished OTM with a nickel-titanium (NiTi) coil spring applying 5-8 g force. Control groups involved the application of NiTi coil spring with and without placebo formulation. The outcome measure included the distance of tooth movement, bone volume fraction, tissue density, and root volume determined with micro-computed tomography. We determined the amount of osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: These formulations were able to sustain the release of RANKL for more than 30 days, and the released RANKL showed a positive effect on mice osteoclast precursor cells (RAW 264.7). Reported injectable RANKL formulations were effective in accelerating OTM compared with other control groups, with 129.2 per cent more tooth movement than no formulation and 71.8 per cent more than placebo formulation, corresponding with a significant increase in the amount of TRAP activity. We did not observe any significant differences in root resorption between the groups. CONCLUSION: Our study shows a significant increase in OTM with injectable formulations containing RANKL.

Augmented reality-assisted training with selected Tai-Chi movements improves balance control and increases lower limb muscle strength in older adults: A prospective randomized trial.

BACKGROUND: Tai-Chi benefits older adults by enhancing balance control and increasing the muscle strength of the lower limbs. However, a complete set of traditional Tai-Chi exercises is sometimes too difficult for beginners. We investigated whether practicing augmented reality-assisted training with selected Tai-Chi movements tailored to the practitioner's ability (selected Tai-Chi, or sTC) is as effective as performing a complete set of Tai-Chi sequences (complete traditional Tai-Chi, or tTC). METHODS: In this prospective randomized trial carried out in the Beitou District of Taipei City, Taiwan, community-dwelling adults aged ≥65 and without any debilitating diseases (n = 28) were included. Participants were randomly assigned to the sTC group (n = 14) or the tTC group (n = 14). Participants in the sTC group practiced selected Tai-Chi movements using the augmented reality Tai-Chi training system. Participants of the tTC group were asked to complete the 24-form Yang-style Tai-Chi following the instructions of Tai-Chi masters. Each training session lasted 30 min, with 3 sessions per week for 8 weeks. Pre- and post-intervention evaluations included functional balance tests, comprising the Berg Balance Scale (BBS), Timed Up and Go test (TUG), and Functional Reach Test (FRT), as well as muscle strength measurements of the lower extremities. RESULTS: Pre-intervention evaluations showed significant differences in FRT (p = 0.034) and left hip abductor muscle strength (p = 0.046) between the sTC and tTC groups. After 8 weeks of training, the BBS, TUG, and FRT scores in the sTC group showed significant improvement overall. Although all three functional balance test scores improved in the tTC group, only the improvement in BBS was statistically significant (p = 0.001). After 8 weeks, all muscle strength measurements increased by an average of 3.1 ± 1.0 kgw in the sTC group and 1.6 ± 0.8 kgw in the tTC group. CONCLUSIONS: The augmented reality-assisted training with selected Tai-Chi movements, designed based on objective measurements of the practitioner's capability, improved balance control and muscle strength of lower limbs at least as effectively as the complete sequence of traditional Tai-Chi exercises. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of National Yang-Ming University (IRB number: 1000087). Written informed consent was obtained from all participants.

Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence.

A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the impact of circulating exosomes on HCC development and recurrence. One-shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha-fetoprotein (AFP), but exosome-free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR-92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR-92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR-92b. The hepatoma-derived exosomal miR-92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell-mediated cytotoxicity. Furthermore, higher expression of miR-92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma-derived exosomal miR-92b. The value of circulating exosomal miR-92b may predict the risk of posttransplant HCC recurrence.

Orthodontic management of a patient with short root anomaly and impacted teeth.

Short root anomaly (SRA) is a rare familial dental condition that is often misdiagnosed. Orthodontic treatment of patients with SRA is challenging because it is difficult to diagnose, it may be accompanied by other dental anomalies, and it has been reported to contribute to additional susceptibility to root resorption during orthodontic treatment. In this article, we describe a methodical and evidence-based means of diagnosing and orthodontically managing a patient with SRA. The patient had additional challenges, including impacted and ectopic teeth. An individualized treatment plan that incorporated efficient and effective mechanics led to a well seated occlusion and an esthetic smile.

The effect of the extent of surgical insult on orthodontic tooth movement.

OBJECTIVE: The primary objective of this study was to investigate how the extent of surgical insult affects the orthodontic tooth movement (OTM) and the alveolar bone modelling and remodelling in a rodent model. MATERIAL AND METHODS: 15-week-old male Wistar rats were used in the research and they were randomly divided into three treatment groups: (1) OTM only (N = 8); (2) OTM + 2 alveolar decortication (AD) (less surgical insult) (N = 8); and (3) OTM + 4 AD (more surgical insult) (N = 8). A nickel-titanium spring delivering 5-8 g of force was used to protract the molar mesially using maxillary incisors as an anchorage. AD was done using a hand piece and a round bur, adjacent to the left first maxillary molar on the palatal alveolar bone. After 14 days of OTM Wistar rats were killed and microfocus computed tomography and histological analysis were performed. RESULTS: The OTM + 4AD group presented with a significant increase (P < 0.05) in the rate of tooth movement when compared to OTM + 2AD group and OTM only group. In addition, the OTM + 4AD group had a significant decrease in bone volume and tissue density (P < 0.05) and a significant increase (P < 0.05) in the trabecular spacing and trabecular thickness when compared to OTM only. Histological quantification of tartrate-resistant acid phosphatase indicated a significant percent increase (P < 0.05) in OTM + 4AD group, when compared to OTM + 2AD and OTM only group. RESULTS: Increased surgical insult increases the rate of OTM. Additionally, increased surgical insult decreases the bone volume and the tissue density.

Multi-point temperature sensing using a linear-cavity lasing system.

A multi-point fiber sensing system formed from a linear cavity laser is proposed. Various optical sensing systems have been investigated, for example, using fiber Bragg grating (FBG) and Brillouin scattering for multi-point sensing. This paper focuses on a simple sensing system by using multi-wavelength lasing with parallel cavities and a semiconductor optical amplifier (SOA). First, optical nonlinearity in amplification of the SOA is discussed to clarify the effects of gain saturation and four-wave mixing on the proposed multi-channel sensing system. And then lasing conditions in the linear cavity laser consisting of an SOA, an arrayed waveguide grating (AWG), and FBGs are theoretically investigated. The multi-wavelength lasing power is found to be limited mainly by gain saturation in the SOA. The lasing power for the eight-channel system is evaluated to be -8.5 dBm when the total loss in the linear cavity is 10 dB. The lasing power can be increased by 3 dB when the channel number is decreased to four. Next, multi-wavelength lasing in the cavity consisting of an SOA, an AWG, a loop mirror, and fiber mirror reflectors is experimentally demonstrated up to eight channels. Finally, two-channel temperature sensing ranging from 13°C to 76°C is experimentally confirmed by using two FBGs as the sensing elements with an AWG having 100-GHz bandwidth.