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Background/purpose: The use of computed tomography (CT) for craniofacial measurements is common in medical imaging, but concerns about accuracy and reliability persist, especially with different CT technologies. This study assessed the accuracy of twenty-six common measurements on consecutive CT images from the same patients, using multidetector CT (MDCT) and cone-beam CT (CBCT) with two software programs (Amira and Dolphin). Materials and methods: Ten adult subjects with consecutive CBCT scans within one year were randomly selected. Another ten subjects with consecutive MDCT scans were paired with the CBCT group based on age, gender, race, occlusion, and craniofacial pattern. All digital imaging and communications in medicine (DICOM) files were randomly coded and analyzed using the two software programs. Intra-examiner reliability was assessed using the intraclass correlation coefficient. Successive measurement errors from consecutive scans for both imaging modalities and software programs were compared. Results: For most skeletal linear and angular measurements, Dolphin showed greater successive measurement errors compared to Amira. Eight of the 26 common measurements had errors greater than one unit (millimeter or degree). Despite almost perfect intra-examiner reliability for upper airway analysis, average successive measurement errors were notably high, particularly for intraoral and oropharyngeal airway volumes. The successive Dolphin measurement error for oropharyngeal airway volume on CBCT images was over three times that on MDCT images. Conclusion: Given the substantial successive measurement errors observed during consecutive CT scanning for the upper airway, this study does not support the quantitative use of CT for analyzing changes in airway dimensions for research purposes.

Abstract Objectives This study aims to develop an innovative approach for monitoring and assessing labor pain through ECG waveform analysis, utilizing machine learning techniques to monitor pain resulting from uterine contractions. Methods The study was conducted at National Taiwan University Hospital between January and July 2020. We collected a dataset of 6010 ECG samples from women preparing for natural spontaneous delivery (NSD). The ECG data was used to develop an ECG waveform-based Nociception Monitoring Index (NoM). The dataset was divided into training (80%) and validation (20%) sets. Multiple machine learning models, including LightGBM, XGBoost, SnapLogisticRegression, and SnapDecisionTree, were developed and evaluated. Hyperparameter optimization was performed using grid search and five-fold cross-validation to enhance model performance. Results The LightGBM model demonstrated superior performance with an AUC of 0.96 and an accuracy of 90%, making it the optimal model for monitoring labor pain based on ECG data. Other models, such as XGBoost and SnapLogisticRegression, also showed strong performance, with AUC values ranging from 0.88 to 0.95. Conclusions This study demonstrates that the integration of machine learning algorithms with ECG data significantly enhances the accuracy and reliability of labor pain monitoring. Specifically, the LightGBM model exhibits exceptional precision and robustness in continuous pain monitoring during labor, with potential applicability extending to broader healthcare settings. Trial registration ClinicalTrials.gov Identifier: NCT04461704.

Abstract Background Degenerative disc disease is one of the most common ailments severely affecting the quality of life in elderly population. Cervical intervertebral body fusion devices are utilized to provide stability after surgical intervention for cervical pathology. In this study, we design a biomimetic porous spinal cage, and perform mechanical simulations to study its performances following American Society for Testing and Materials International (ASTM) standards before manufacturing to improve design process and decrease cost and consumption of material. Methods The biomimetic porous Ti-6Al-4 V interbody fusion devices were manufactured by selective laser melting (laser powder bed fusion: LPBF in ISO/ASTM 52900 standard) and subsequently post-processed by using hot isostatic pressing (HIP). Chemical composition, microstructure and the surface morphology were studied. Finite element analysis and in vitro biomechanical test were performed. Findings The post heat treatment can optimize its mechanical properties, as the stiffness of the cage decreases to reduce the stress shielding effect between two instrumented bodies. After the HIP treatment, the ductility and the fatigue performance are substantially improved. The use of HIP post-processing can be a necessity to improve the physical properties of customized additive manufacturing processed implants. Interpretation In conclusion, we have successfully designed a biomimetic porous intervertebral device. HIP post-treatment can improve the bulk material properties, optimize the device with reduced stiffness, decreased stress shielding effect, while still provide appropriate space for bone growth. Clinical significance The biomechanical performance of 3-D printed biomimetic porous intervertebral device can be optimized. The ductility and the fatigue performance were substantially improved, the simultaneously decreased stiffness reduces the stress shielding effect between two instrumented bodies; while the biomimetic porous structures provide appropriate space for bone growth, which is important in the patients with osteoporosis.

Background/Purpose: Crestal bone stability, implant rigidity and occlusal loading are issues with small-diameter implants. This article demonstrates the use of two small-diameter implants replacing a missing wide edentulous site and discusses factors that may affect bone changes. Methods: Patients who wanted to restore an edentulous space measuring from 12 to 14 mm wide in the posterior region were offered an alternative treatment option, using two narrow or regular-diameter implants instead of one wide implant. In the study, the crestal bone stability of 12 implants in 6 edentulous sites was assessed by cone beam CTs and periapical radiographs in follow-up visits for up to 4 years. Results: The bone level of all the implants was stable at buccal, lingual, mesial and distal sites, with mean values

Abstract Current rat alveolar ridge preservation models have not been well standardized. In this study, we proposed decoronation-induced infected alveolar socket model of rat. The bilateral maxillary first molars (M1) of twenty-four rats were decoronized or extracted. After 2, 6, 10, and 14 weeks, bone and soft tissue changes at M1 and periodontal conditions of maxillary second (M2) and third molars (M3) were evaluated by micro-computed tomography and histological analysis. Additional eighteen rats with standardized size defects were grafted with Bio-Oss Collagen to compare with unmanipulated contralateral side. Decoronation preserved greater bone and soft tissue dimensions at M1, provided larger three-dimensional (3D) bone contour volume, but also promoted periodontal breakdown of M2 Histological results showed intense inflammatory cell infiltrations and severe bone resorption within M1 socket and at mesial aspect of M2. The critical dimensions to accommodate largest standardized defect at M1 were 2.2–2.3 mm at vertical bone height and 2.8–3.2 mm at alveolar crestal width. Bio-Oss Collagen could not fully preserve buccal or palatal bone height but could be beneficial in preserving ridge width in large alveolar defects. Collectively, if periodontally-involved alveolar bone defect is preferred, we suggest extracting M1 roots 6 weeks after decoronation to allow periodontitis to occur at M2. If standardized critical dimension defect is preferred, we suggest extracting M1 roots 2 weeks after decoronation, and creating defect in the middle of M1 site with size no larger than 2.7 mm diameter to its full depth.

IntroductionSpinal cord injury (SCI) is a devastating neurological disorder with an enormous impact on individual's life and society. A reliable and reproducible animal model of SCI is crucial to have a deeper understanding of SCI. We have developed a large-animal model of spinal cord compression injury (SCI) with integration of multiple prognostic factors that would have applications in humans.MethodsFourteen human-like sized pigs underwent compression at T8 by implantation of an inflatable balloon catheter. In addition to basic neurophysiological recording of somatosensory and motor evoked potentials, we introduced spine-to-spine evoked spinal cord potentials (SP-EPs) by direct stimulation and measured them just above and below the affected segment. A novel intraspinal pressure monitoring technique was utilized to measure the actual pressure on the cord. The gait and spinal MRI findings were assessed in each animal postoperatively to quantify the severity of injury.ResultsWe found a strong negative correlation between the intensity of pressure applied to the spinal cord and the functional outcome (P < 0.0001). SP-EPs showed high sensitivity for real time monitoring of intraoperative cord damage. On MRI, the ratio of the high-intensity area to the cross-sectional of the cord was a good predictor of recovery (P < 0.0001).ConclusionOur balloon compression SCI model is reliable, predictable, and easy to implement. By integrating SP-EPs, cord pressure, and findings on MRI, we can build a real-time warning and prediction system for early detection of impending or iatrogenic SCI and improve outcomes.

Background: Tigecycline is an antibiotic that well tolerated for treating complicated infections. It has received attention as an anti-cancer agent and expected to solve two major obstacles, sides effects that accompany chemotherapy and drug resistance, in the breast cancer treatment. However, previous studies reported that the levels in the blood are typically low of tigecycline, so higher doses are needed to treat cancer, that may increase the risk of side effects. To achieve better anti-cancer effects for tigecycline, we need to find a novel adjunct agent. Methods: In this study, we used different concentration of pyrvinium pamoate combined with tigecycline to treat cell. And assess the effect of two drugs in inhibit cell proliferation, induce cell autophagy, or increase cell apoptosis to evaluate the consequent of combined therapy. Results: We observed that after the combined therapy, the cell cycle arrest at G1/s phase, the level of p21 increased, but decreased the levels of CDK2. Others, two drugs via different mechanisms to inhibit cancer cell proliferation and with selective cytotoxic to different cell lines. That could enhance the effect of breast cancer treatment. Conclusion: Combining low dose of tigecycline use with pyrvinium pamoate is a novel approach for breast cancer treatment. Appropriate combined therapy in breast cancer is recommended to improve outcomes. Other problems like drug resistance occur in patients or the microbes surrounding breast tissues would confer susceptibility to cancers then influence the effectiveness of treatment, which could be improved through combined therapy.

Osteoarthritis is a prevalent musculoskeletal disorder in the elderly, which leads to high rates of morbidity. Mesenchymal stem cells (MSCs) are a promising approach to promote tissue regeneration in the absence of effective long-term treatments. Small molecules are relatively inexpensive and can selectively alter stem cell behavior during their differentiation, making them an attractive option for clinical applications. In this study, we developed an extracellular matrix (ECM)-based biphasic scaffold (BPS) loaded with two small-molecule drugs, kartogenin (KGN) and metformin (MET). This cell-free biomimetic biphasic scaffold consists of a bone (gelatin/hydroxyapatite scaffold embedded with metformin [GHSM]) and cartilage (nano-gelatin fiber embedded with kartogenin [NGFK]) layer designed to stimulate osteochondral regeneration. Extracellular matrix (ECM)-based biomimetic scaffolds can promote native cell recruitment, infiltration, and differentiation even in the absence of additional growth factors. The biphasic scaffold (BPS) showed excellent biocompatibility in vitro, with mesenchymal stem cells (MSCs) adhering, proliferating, and differentiated on the biomimetic biphasic scaffolds (GHSM and NGFK layers). The biphasic scaffolds upregulated both osteogenic and chondrogenic gene expression, sulfated glycosaminoglycan (sGAG), osteo- and chondrogenic biomarker, and relative mRNA gene expression. In an in vivo rat model, histo-morphological staining showed effective regeneration of osteochondral defects. This novel BPS has the potential to enhance both subchondral bone repair and cartilage regeneration, demonstrating excellent effects on cell homing and the recruitment of endogenous stem cells.

Background/Purpose: Alveolar bone loss following peri-implantitis remains a clinical challenge. We aimed to design a novel bioactive dental implant to accommodate the large bone defect caused by removal of previously failed implant. Methods: Bio-ActiveITRI dental implant was manufactured with laser-sintered additive 3D printing technique. A 7.5 mm diameter × 7.0 mm depth osteotomy defect was created at the lateral aspect of distal femur of 20 New Zealand white rabbits to simulate the bony defect after removal of failed dental implant. One side of distal femurs was randomly selected for the commercially pure titanium NobelActive™ implant (control group) and the other side with Bio-ActiveITRI Ti6Al4V porous dental implant (ITRI group). Animals were sacrificed at 4, 8 and 12 weeks after the implants' insertion. The samples were processed for gross morphological analysis, radiographic examination, micro-CT evaluation, and mechanical testing. Results: In histomorphometrical evaluation and micro-CT analysis, active new bone formation and good osseointegration within the ITRI implants were observed at the bone gap surrounding the dental implants. The biomechanical parameters in the Bio-ActiveITRI dental implants were significantly higher than those of the commercially control samples. For the Bio-ActiveITRI dental implants, the trabecular thickness decreased, while the trabecular separation and total porosity increased from the prescribed 1-month to 3-month time points; reflecting the natural remodeling of surrounding bony tissue in the Bio-ActiveITRI dental implants. Conclusion: The novel porous structured Bio-ActiveITRI dental implants may have a great potential for the prosthetic reconstruction where bone support is compromised after removal of a previously failed implant. Keywords: Bio-ActiveITRI dental implant, Bone defect, Laser-sintered additive 3D printing

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types—manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)—were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.

Abstract Background Polymethylmethacrylate bone cement has a variety of applications in orthopedic surgery, but it also has some shortcomings such as high heat generation during polymerization and poor integration with bone tissue. In this study, a bio-composite bone cement composed of tri-calcium phosphate and chitosan as additives to acrylic bone cement was developed. Our hypothesis is that this new bio-composite bone cement has a better osteo-integration than pure polymethyl methacrylate cement. Methods Physiological composition, i.e., 65 wt% inorganic and 35 wt% organic components, of tri-calcium phosphate and chitosan contents was selected as degradable additives to replace acrylic bone cement. A series of properties such as exothermic temperature changes, setting time, bio-mechanical characteristics, degradation behaviors, and in vitro cytotoxicity were examined. Preliminary in vivo animal study was also performed. Results The results showed that the bio-composite bone cement exhibited lower curing temperature, longer setting time, higher weight loss and porosity after degradation, lower compressive Young’s modulus, and ultimate compressive strength as compared with those of pure polymethyl methacrylate cement. Cell proliferation tests demonstrated that the bio-composite bone cement was non-cytotoxic, and the in vivo tests revealed that was more osteo-conductive. Conclusions The results indicated that the modified chitosan/tri-calcium phosphate/polymethyl methacrylate bio-composites bone cement could be degraded gradually and create rougher surfaces that would be beneficial to cell adherence and growth. This new bio-composite bone cement has potential in clinical application. Our future studies will focus on long-term implantation to investigate the stability of the bio-composite bone cement in long-term implantation.

Abstract Background The management of complaints in the setting of intensive care may provide opportunities to understand patient and family experiences and needs. However, there are limited reports on the structured application of complaint analysis tools and comparisons between healthcare complaints in the critical care setting and other settings. Methods From the complaint management database of a university-affiliated medical center in Taiwan, we retrospectively identified the records of healthcare complaints to the intensive care units (ICUs) from 2008 to 2016. Complaints to the general wards in the same period were randomly selected from the database with twice the number of that of the ICU complaints. We coded, typed, and compared the complaints from the two settings according to the Healthcare Complaint Analysis Tool. Results We identified 343 complaints to the ICUs and randomly selected 686 complaints to the general wards during the 9-year study period. Most (94.7%) of the complaints to the ICUs came from the family members, whereas more complaints to the general wards came from the patients (44.2%). A total of 1529 problems (441 from ICU and 818 from general wards) were identified. Compared with the general ward complaints, in the ICU there were more complaints with multiple problems (25.1% vs. 16.9%, p = 0.002), complaints were referred more frequently to the nurses (28.1% vs. 17.5%, p

Aim Intrahospital transportation (IHT) of patients under mechanical ventilation (MV) significantly increases the risk of patient harm. A structured process performed by a well-prepared team with adequate communication among team members plays a vital role in enhancing patient safety during transportation.Design and implementation We conducted this quality improvement programme at the intensive care units of a university-affiliated medical centre, focusing on the care of patients under MV who received IHT for CT or MRI examinations. With the interventions based on the analysis finding of the IHT process by healthcare failure mode and effects analysis, we developed and implemented strategies to improve this process, including standardisation of the transportation process, enhancing equipment maintenance and strengthening the teamwork among the transportation teammates. In a subsequent cycle, we developed and implemented a new process with the practice of reminder-assisted briefing. The reminders were printed on cards with mnemonics including ‘VITAL’ (Vital signs, Infusions, Tubes, Alarms and Leave) attached to the transportation monitors for the intensive care unit nurses, ‘STOP’ (Secretions, Tubes, Oxygen and Power) attached to the transportation ventilators for the respiratory therapists and ‘STOP’ (Speak-out, Tubes, Others and Position) attached to the examination equipment for the radiology technicians. We compared the incidence of adverse events and completeness and correctness of the tasks deemed to be essential for effective teamwork before and after implementing the programme.Results The implementation of the programme significantly reduced the number and incidence of adverse events (1.08% vs 0.23%, p=0.01). Audits also showed improved teamwork during transportation as the team members showed increased completeness and correctness of the essential IHT tasks (80.8% vs 96.5%, p

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.

Abstract Background When bacteria colony persist within a biofilm, suitable drugs are not yet available for the eradication of biofilm-producing bacteria. The aim of this study is to study the effect of magnetic nano-particles-induced hyperthermia on destroying biofilm and promoting bactericidal effects of antibiotics in the treatment of osteomyelitis. Methods Sixty 12-weeks-old male Wistar rats were used. A metallic 18G needle was implanted into the bone marrow cavity of distal femur after the injection of Methicillin-sensitive Staphylococcus aureus (MSSA). All animals were divided into 5 different treatment modalities. The microbiological evaluation, scanning electron microscope examination, radiographic examination and then micro-CT evaluation of peri-implant bone resorption were analyzed. Results The pathomorphological characteristics of biofilm formation were completed after 40-days induction of osteomyelitis. The inserted implants can be heated upto 75 °C by magnetic heating without any significant thermal damage on the surrounding tissue. We also demonstrated that systemic administration of vancomycin [VC (i.m.)] could not eradicate the bacteria; but, local administration of vancomycin into the femoral canal and the presence of magnetic nanoparticles hyperthermia did enhance the eradication of bacteria in a biofilm-based colony. In these two groups, the percent bone volume (BV/TV: %) was significantly higher than that of the positive control. Conclusions For the treatment of chronic osteomyelitis, we developed a new modality to improve antibiotic efficacy; the protection effect of biofilms on bacteria could be destroyed by magnetic nanoparticles-induced hyperthermia and therapeutic effect of systemic antibiotics could be enhanced.

Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of Acan, Sox9, and Col2a1 was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering.

Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel; the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.

There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.

OBJECTIVE:There have been concerns about the workplace interpersonal conflict (WIC) among healthcare workers. As healthcare organizations have applied the incident reporting system (IRS) widely for safety-related incidents, we proposed that this system might provide a channel to explore the WICs. METHODS:We retrospectively reviewed the reports to the IRS from July 2010 to June 2013 in a medical center. We identified the WICs and typed these conflicts according to the two foci (task content/process and interpersonal relationship) and the three properties (disagreement, interference, and negative emotion), and analyzed relevant data. RESULTS:Of the 147 incidents with WIC, the most common related processes were patient transfer (20%), laboratory tests (17%), surgery (16%) and medical imaging (16%). All of the 147 incidents with WIC focused on task content or task process, but 41 (27.9%) also focused on the interpersonal relationship. We found disagreement, interference, and negative emotion in 91.2%, 88.4%, and 55.8% of the cases, respectively. Nurses (57%) were most often the reporting workers, while the most common encounter was the nurse-doctor interaction (33%), and the majority (67%) of the conflicts were experienced concurrently with the incidents. There was a significant difference in the distribution of worker job types between cases focused on the interpersonal relationship and those without (p = 0.0064). The doctors were more frequently as the reporter when the conflicts focused on the interpersonal relationship (34.1%) than not on it (17.0%). The distributions of worker job types were similar between those with and without negative emotion (p = 0.125). CONCLUSIONS:The institutional IRS is a useful place to report the workplace interpersonal conflicts actively. The healthcare systems need to improve the channels to communicate, manage and resolve these conflicts.

Genomic studies have revealed that there is a significant association between a point mutation of the human Col2A1 gene (G1170S) and several hip disorders. The purpose of the study was to explore the phenotype and altered cartilage matrix homeostasis of transgenic mice carrying this mutated Col2a1 gene. Methods: Wild-type and transgenic mice were used as the control and study groups, respectively. Body weight measurement, radiographic analysis, and histological analysis of the mice were carried out to describe differences between the wild-type and transgenic mice at different ages. Cartilage metabolism studies were also carried out, including an MTT assay of cellular proliferation and nitric oxide and glycosaminoglycan assays. Allelic expression levels of the mutant A allele and the normal G allele were established by TaqMan assay. Cytokine and protease gene expression were measured. Results: Transgenic mice had a lower mean body weight, a deformed skeletal structure, and abnormal cartilage histomorphology. Chondrocyte proliferation was significantly compromised and this was linked to significantly higher NO secretion and less soluble glycosaminoglycan formation. TNF-α and IL-1β gene expression was significantly upregulated, while MMP-13 gene expression was significantly downregulated. Conclusion: The mutant G1170S Col2a1 gene in mice clearly alters the transgenic murine phenotype and cartilage matrix homeostasis.

A mismatch of elastic modulus values could result in undesirable bone resorption around the dental implant. The objective of this study was to optimize direct metal laser sintering (DMLS)-manufactured Ti6Al4V dental implants’ design, minimize elastic mismatch, allow for maximal bone ingrowth, and improve long-term fixation of the implant. In this study, DMLS dental implants with different morphological characteristics were fabricated. Three-point bending, torsional, and stability tests were performed to compare the mechanical properties of different designs. Improvement of the weaker design was attempted by augmentation with a longitudinal 3D-printed strut. The osseointegrative properties were evaluated. The results showed that the increase in porosity decreased the mechanical properties, while augmentation with a longitudinal weight-bearing strut can improve mechanical strength. Maximal alkaline phosphatase gene expression of MG63 cells attained on 60% porosity Ti6Al4V discs. In vivo experiments showed good incorporation of bone into the porous scaffolds of the DMLS dental implant, resulting in a higher pull-out strength. In summary, we introduced a new design concept by augmenting the implant with a longitudinal weight-bearing strut to achieve the ideal combination of high strength and low elastic modulus; our results showed that there is a chance to reach the balance of both biologic and mechanical demands.

Technetium-99m methylene diphosphonate (Tc-99m MDP) whole-body bone scintigraphy (BS) has been widely used for detecting bone metastases. The aim of this study is to investigate the diagnostic accuracy of BS in detecting skeletal metastases for hepatocellular carcinoma (HCC) patients. In addition, the anatomic distribution of the metastatic bone lesions and the prognoses of the HCC patients are also analyzed. Methods: We retrospectively reviewed BS results of 179 consecutive HCC patients from January 2005 to December 2006 in our institution. The false negative (FN) rate, sensitivity, and specificity of BS were evaluated by patient-based and region-based analyses. Results: A total of 59 patients (33.0%) were confirmed of bone metastases. A total of 25 of these 59 patients (46.3%) had at least one lesion categorized as BS FN, and the bone metastatic status for 10 patients (17.0%) was underestimated by BS. The most observed metastatic site was spine while the most observed sites with FN of BS were the lower extremity. In total, there were 122 metastatic regions and 33 regions (27.0%) were FN of BS. Patients without any metastases survived significantly longer than any of other groups with metastases. Conclusion: High FN rate of Tc-99m MDP BS in detecting metastatic bone lesions for HCC patients was observed. In our opinion, careful history taking, meticulous examination, and a high index of suspicion are important for HCC patients with unexplained progressive pain in the musculoskeletal system. Even with negative results from Tc-99m MDP BS, the possibility of skeletal metastases cannot be indiscriminately excluded.

Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes. Specifically, non-tenogenic gene expression, adipogenic potential, cell migration rate, filamentous actin expression, and the activation of signaling pathways were analyzed in tenocytes treated with high glucose, followed by the presence or absence of mechanical stretch. We analyzed tenocyte phenotype in vivo by immunohistochemistry using an STZ (streptozotocin)-induced long-term diabetic mouse model. High glucose-treated tenocytes expressed higher levels of the adipogenic transcription factors PPARγ and C/EBPs. PPARγ was also highly expressed in diabetic tendons. In addition, increased adipogenic differentiation and decreased cell migration induced by high glucose implicated a fibroblast-to-adipocyte phenotypic change. By applying mechanical stretch to tenocytes in high-glucose conditions, adipogenic differentiation was repressed, while cell motility was enhanced, and fibroblastic morphology and gene expression profiles were strengthened. In part, these effects resulted from a stretch-induced activation of ERK (extracellular signal-regulated kinases) and a concomitant inactivation of Akt. Our results show that mechanical stretch alleviates the augmented adipogenic transdifferentiation potential of high glucose-treated tenocytes and helps maintain their fibroblastic characteristics. The alterations induced by high glucose highlight possible pathological mechanisms for diabetic tendinopathy. Furthermore, the beneficial effects of mechanical stretch on tenocytes suggest that an appropriate physical load possesses therapeutic potential for diabetic tendinopathy.

Various kinds of three-dimensional (3D) scaffolds have been designed to mimic the biological spontaneous bone formation characteristics by providing a suitable microenvironment for osteogenesis. In view of this, a natural bone-liked composite scaffold, which was combined with inorganic (hydroxyapatite, Hap) and organic (type I collagen, Col) phases, has been developed through a self-assembly process. This 3D porous scaffold consisting of a c-axis of Hap nanocrystals (nHap) aligning along Col fibrils arrangement is similar to natural bone architecture. A significant increase in mechanical strength and elastic modulus of nHap/Col scaffold is achieved through biomimetic mineralization process when compared with simple mixture of collagen and hydroxyapatite method. It is suggested that the self-organization of Hap and Col produced in vivo could also be achieved in vitro. The oriented nHap/Col composite not only possesses bone-like microstructure and adequate mechanical properties but also enhances the regeneration and reorganization abilities of bone tissue. These results demonstrated that biomimetic nHap/Col can be successfully reconstructed as a bone graft substitute in bone tissue engineering.

INTRODUCTION: Treatment for osteoporosis commonly includes the use of bisphosphonates. Serious side effects of these drugs are caused by the inhibition of bone resorption as a result of osteoclast apoptosis. Treatment using calcitonin along with bisphosphonates overcomes these side-effects in some patients. Calcitonin is known to inhibit bone resorption without reducing the number of osteoclasts and is thought to prolong osteoclast survival through the inhibition of apoptosis. Further understanding of how calcitonin inhibits apoptosis could prove useful to the development of alternative treatment regimens for osteoporosis. This study aimed to analyze the mechanism by which calcitonin influences osteoclast apoptosis induced by a bisphosphate analog, sintered dicalcium pyrophosphate (SDCP), and to determine the effects of co-treatment with calcitonin and SDCP on apoptotic signaling in osteoclasts. METHODS: Isolated osteoclasts were treated with CT, SDCP or both for 48 h. Osteoclast apoptosis assays, pit formation assays, and tartrate-resistant acid phosphatase (TRAP) staining were performed. Using an osteoporosis rat model, ovariectomized (OVX) rats received calcitonin, SDCP, or calcitonin + SDCP. The microarchitecture of the fifth lumbar trabecular bone was investigated, and histomorphometric and biochemical analyses were performed. RESULTS: Calcitonin inhibited SDCP-induced apoptosis in primary osteoclast cultures, increased Bcl-2 and Erk activity, and decreased Mcl-1 activity. Calcitonin prevented decreased osteoclast survival but not resorption induced by SDCP. Histomorphometric analysis of the tibia revealed increased bone formation, and microcomputed tomography of the fifth lumbar vertebrate showed an additive effect of calcitonin and SDCP on bone volume. Finally, analysis of the serum bone markers CTX-I and P1NP suggests that the increased bone volume induced by co-treatment with calcitonin and SDCP may be due to decreased bone resorption and increased bone formation. CONCLUSIONS: Calcitonin reduces SDCP-induced osteoclast apoptosis and increases its efficacy in an in vivo model of osteoporosis.