Frailty and Other Factors Associated With Early Outcomes in Middle-to Older Age Trauma Patients: A Prospective Cohort Study.

OBJECTIVES: To prospectively investigate associations of frailty and other predictor variables with functional recovery and health outcomes in middle-aged and older patients with trauma. DESIGN: Single-center prospective cohort study. SETTING: Emergency department of Wan Fang Hospital in Taiwan. PARTICIPANTS: Trauma patients aged 45 and older. MEASUREMENTS: Frailty was assessed with the Clinical Frailty Scale (CFS). Injury mechanisms, pre-existing diseases, and fracture locations were recorded at baseline. The primary outcome was functional recovery assessed using the Barthel Index (BI). Secondary outcomes were new care needs, unscheduled return visits, and falls 3 months postinjury. RESULTS: A total of 588 participants were included in the final analysis. For every one-point increase in the CFS, the multivariable-adjusted odds ratio (OR, 95% confidence interval [CI]) of failure to retain the preinjury BI was 1.34 (1.16-1.55); associations were consistent across levels of age and injury severities. Significant joint associations of frailty and age with poor functional recovery were observed. CFS was also associated with new care needs (OR for every one-point increase, 1.36, 95% CI, 1.17-1.58), unscheduled return visits (OR 1.26, 95% CI, 1.04-1.51), and falls (OR 1.23, 95% CI, 1.01-1.51). Other variables associated with failure to retain preinjury BI included road traffic accident and presence of hip fracture. CONCLUSION: Frailty was significantly associated with poor functional and health outcomes regardless of injury severity in middle-aged and older patients with trauma. Injury mechanisms and fracture locations were also significant predictors of functional recovery postinjury.

Prediction of posttraumatic functional recovery in middle-aged and older patients through dynamic ensemble selection modeling.

Introduction: Age-specific risk factors may delay posttraumatic functional recovery; complex interactions exist between these factors. In this study, we investigated the prediction ability of machine learning models for posttraumatic (6 months) functional recovery in middle-aged and older patients on the basis of their preexisting health conditions. Methods: Data obtained from injured patients aged ≥45 years were divided into training-validation (n = 368) and test (n = 159) data sets. The input features were the sociodemographic characteristics and baseline health conditions of the patients. The output feature was functional status 6 months after injury; this was assessed using the Barthel Index (BI). On the basis of their BI scores, the patients were categorized into functionally independent (BI >60) and functionally dependent (BI ≤60) groups. The permutation feature importance method was used for feature selection. Six algorithms were validated through cross-validation with hyperparameter optimization. The algorithms exhibiting satisfactory performance were subjected to bagging to construct stacking, voting, and dynamic ensemble selection models. The best model was evaluated on the test data set. Partial dependence (PD) and individual conditional expectation (ICE) plots were created. Results: In total, nineteen of twenty-seven features were selected. Logistic regression, linear discrimination analysis, and Gaussian Naive Bayes algorithms exhibited satisfactory performances and were, therefore, used to construct ensemble models. The k-Nearest Oracle Elimination model outperformed the other models when evaluated on the training-validation data set (sensitivity: 0.732, 95% CI: 0.702-0.761; specificity: 0.813, 95% CI: 0.805-0.822); it exhibited compatible performance on the test data set (sensitivity: 0.779, 95% CI: 0.559-0.950; specificity: 0.859, 95% CI: 0.799-0.912). The PD and ICE plots showed consistent patterns with practical tendencies. Conclusion: Preexisting health conditions can predict long-term functional outcomes in injured middle-aged and older patients, thus predicting prognosis and facilitating clinical decision-making.

Association between short-term air pollution exposure and traumatic intracranial hemorrhage: pilot evidence from Taiwan.

Introduction: The detrimental effects of air pollution on the brain are well established. However, few studies have examined the effect of air pollution on traumatic brain injury (TBI). This pilot study evaluated the association between short-term air pollution exposure and traumatic intracranial hemorrhage (TIH). Methods: Hospital data of patients with TBI following road traffic accidents were retrospectively collected from the electronic medical records at five trauma centers in Taiwan between 1 January and 31 December 2017. TIH was employed as an outcome measure. All road accident locations were geocoded, and air quality data were collected from the nearest monitoring stations. Air pollutants were entered into five multivariable models. A sensitivity analysis was performed on patients who are vulnerable to suffering TBI after road accidents, including motorcyclists, bicyclists, and pedestrians. Results: Among 730 patients with TBI, 327 had TIH. The ages of ≥65 [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.85-5.70], 45-64 (OR, 2.61; 95% CI, 1.64-4.15), and 25-44 (OR, 1.79; 95% CI, 1.13-2.84) years were identified as significant risk factors in the multivariable analysis. In the best-fit multivariable model, exposure to higher concentrations of particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) was associated with an elevated TIH risk (OR, 1.50; 95% CI, 1.17-1.94). The concentration of nitrogen oxides (NOX) did not increase the risk of TIH (OR, 0.45; 95% CI, 0.32-0.61). After categorizing the air pollution concentration according to quartile, the trend tests in the multivariate model showed that the concentrations of PM2.5 and NOX were significant (p = 0.017 and p < 0.001, respectively). There was a negative borderline significant association between temperature and TIH risk (OR, 0.75; 95% CI, 0.56-1.00, p = 0.05). Notably, the single-vehicle crash was a significant risk factor (OR, 2.11; 95% CI, 1.30-3.42) for TIH. Discussion: High PM2.5 concentrations and low temperatures are risk factors for TIH in patients with TBI. High NOX concentrations are associated with a lower TIH risk.

Environmental Factors Associated with Severe Motorcycle Crash Injury in University Neighborhoods: A Multicenter Study in Taiwan.

University neighborhoods in Taiwan have high-volume traffic, which may increase motorcyclists' risk of injury. However, few studies have analyzed the environmental factors affecting motorcycle crash injury severity in university neighborhoods. In this multicenter cross-sectional study, we explored the factors that increase the severity of such injuries, especially among young adults. We retrospectively connected hospital data to the Police Traffic Accident Dataset. Areas within 500 m of a university were considered university neighborhoods. We analyzed 4751 patients, including 513 with severe injury (injury severity score ≥ 8). Multivariate analysis revealed that female sex, age ≥ 45 years, drunk driving, early morning driving, flashing signals, and single-motorcycle crashes were risk factors for severe injury. Among patients aged 18-24 years, female sex, late-night and afternoon driving, and flashing signals were risk factors. Adverse weather did not increase the risk. Time to hospital was a protective factor, reflecting the effectiveness of urban emergency medical services. Lifestyle habits among young adults, such as drunk driving incidents and afternoon and late-night driving, were also explored. We discovered that understanding chaotic traffic in the early morning, flashing signals at the intersections, and roadside obstacles is key for mitigating injury severity from motorcycle crashes in university neighborhoods.

Foraging for the Optimal Dressing Scaffold to Carry Adipose-Derived Stromal/Progenitor Cells for Cell Therapy.

In our daily plastic surgery practice, we have seen many chronic wounds that need new biotechnology to help and improve wound healing. Stem cells play a crucial role in regenerative medicine. Many pre-clinical researches had reported the beneficial paracrine effects of stem cell therapy for chronic wounds. Cell-friendly scaffolds may provide the protection and three-dimensional space required for adherence of stem cells, thus allowing these stem cells to proliferate and differentiate for treatment purpose. A successful scaffold may enhance the effects of stem cell therapy. In this presented series, the authors attempted to identify the most suitable scaffolds from several commercially available wound dressings that could sustain adipose-derived stromal/progenitor cells (ADSCs) survival. Therefore, we isolated ADSCs containing the green fluorescent protein (GFP) from GFP transgenic rats. The GFP (+) ADSCs and their progenies could be easily observed using a fluorescence microscope. Moreover, we analyzed the cytokines secreted in condition medium (CM) to understand the activities of ADSCs in various dressings. Our results showed that the foam dressings, hydrofiber, chitosan, and alginate plus carboxymethylcellulose were identified as the most suitable dressing materials. Higher concentrations of transforming growth factor beta (TGF-ß) and vascular endothelial growth factor (VEGF) were observed 48 h after loading them with GFP (+) ADSCs. Therefore, multiple topical cell therapy using ADSCs can be performed by applying suitable dressing scaffolds without repeated needle injections to deliver the stem cells into the wound bed. Based on their fluorescence property, the GFP (+) ADSCs can also possibly be used for testing biocompatibility of medical materials in the future.

Association of Air Pollution and Weather Factors with Traffic Injury Severity: A Study in Taiwan.

Exposure to air pollutants may elevate the injury severity scores (ISSs) for road traffic injuries (RTIs). This multicenter cross-sectional study aimed to investigate the associations between air pollution, weather conditions, and RTI severity. This retrospective study was performed in Taiwan in 2018. The location of each road traffic accident (RTA) was used to determine the nearest air quality monitoring and weather station, and the time of each RTA was matched to the corresponding hourly air pollutant concentration and weather factors. Five multiple logistic regression models were used to compute the risk of sustaining severe injury (ISS ≥ 9). Of the 14,973 patients with RTIs, 2853 sustained severe injury. Moderate or unhealthy air quality index, higher exposure to particulate matter ≤2.5 µm in diameter, bicyclists or pedestrians, greater road width, nighttime, and higher temperature and relative humidity were significant risk factors for severe injury. Exposure to nitrogen oxide and ozone did not increase the risk. Auto occupants and scene-to-hospital time were the protective factors. Sensitivity analyses showed consistent results between air pollutants and the risk of severe injury. Poor air quality and hot and humid weather conditions were associated with severe RTIs. Active commuters were at higher risk of sustaining severe RTI.

Effects of the COVID-19 Pandemic on Treatment Efficiency for Traumatic Brain Injury in the Emergency Department: A Multicenter Study in Taiwan.

The coronavirus disease 2019 (COVID-19) pandemic has impacted emergency department (ED) practice, including the treatment of traumatic brain injury (TBI), which is commonly encountered in the ED. Our study aimed to evaluate TBI treatment efficiency in the ED during the COVID-19 pandemic. A retrospective observational study was conducted using the electronic medical records from three hospitals in metropolitan Taipei, Taiwan. The time from ED arrival to brain computed tomography (CT) and the time from ED arrival to surgical management were used as measures of treatment efficiency. TBI treatment efficiencies in the ED coinciding with a small-scale local COVID-19 outbreak in 2020 (P1) and large-scale community spread in 2021 (P2) were compared against the pre-pandemic efficiency recorded in 2019. The interval between ED arrival and brain CT was significantly shortened during P1 and P2 compared with the pre-pandemic interval, and no significant delay between ED arrival and surgical management was found, indicating increased treatment efficiency for TBI in the ED during the COVID-19 pandemic. Minimizing viral spread in the community and the hospital is vital to maintaining ED treatment efficiency and capacity. The ED should retain sufficient capacity to treat older patients with serious TBI during the COVID-19 pandemic.

Butein induces cellular senescence through reactive oxygen species-mediated p53 activation in osteosarcoma U-2 OS cells.

Butein is a flavonoid isolated from various medicinal plants. It is known to have different biological activities including anti-inflammation, anti-adipogenesis, and anti-angiogenesis. In the study, we demonstrated the anti-proliferative effect of butein in human osteosarcoma U-2 OS cells. Our data showed that butein significantly suppressed the viability and colony formation ability of U-2 OS cells. Further experiments revealed butein exposure resulted in a cell cycle arrest at S and G2/M phase in U-2 OS cells. Importantly, we found that butein activated the tumor suppressor p53, and trigged a p53-dependent senescence in U-2 OS cells. Knockdown of p53 suppressed the senescence and rescued the viability in butein-treated U-2 OS cells. Furthermore, we observed that butein exposure significantly enhanced reactive oxygen species (ROS) levels in U-2 OS cells. Co-administration of the ROS inhibitor NAC largely abolished the up-regulated p53 protein level, and rescued the suppressed viability and colony formation ability in butein-exposed U-2 OS cells. Taken together, our data proposed the increased ROS by butein exposure activated p53, and the activated p53 was involved in the anti-proliferative effect of butein via inducing senescence in U-2 OS cells. This report suggests that butein is a promising candidate for cancer therapy against osteosarcoma.

Acute chorioamnionitis complicated with symmetrical peripheral gangrene.

OBJECTIVE: Symmetrical peripheral gangrene (SPG) is an uncommon but important clinical syndrome. We present a case of acute chorioamnionitis complicated with SPG. CASE REPORT: A 33-year-old female (gravida 5, para 2) was admitted with preterm premature rupture of membranes (PPROM) at 20 weeks and four days of gestation. She received cervical cerclage four days ago. Seven days after the diagnosis of PPROM, she developed fever, tachypnea and tachycardia. Termination of pregnancy was decided for clinical diagnosis of sepsis. After the abortus was born, gangrene change on the nose was noticed. Afterwards, this patient developed acrocyanosis of extremities. SPG developed following sepsis with intravascular disseminated coagulation (DIC). After intensive care, the patient underwent hyperbaric oxygen therapy and fasciectomy of the left forearm. CONCLUSION: We suggest awareness of SPG associated with acute chorioamnionitis. Early recognition of SPG, multidisciplinary care, and treatment of its underlying conditions are the mainstays of management.

Rider factors associated with severe injury after a light motorcycle crash: A multicentre study in an emerging economy setting.

OBJECTIVE: In Taiwan, light motorcycles (LMCs) with cylinder capacities between 50 and 250 cc are widely used for daily commute. These vehicles are operated in a mixed traffic environment and prohibited on highways. In light of increasing motorcycle casualties, we conducted a multicentre study to analyse rider factors affecting injury severity. METHODS: Riders hospitalised upon LMC crashes were contacted. Information on demographics, comorbidities, and riding behaviours was collected through questionnaires and linked to hospital data. The injury severity score (ISS) and length of hospitalisation (LOH) were used as injury severity measures. RESULTS: In total, 725 patients (mean age: 37.7 years; 64% men) completed their questionnaires. Multivariate analysis results showed that age ≥ 65 years, half-face helmets, protective clothing, collisions with a bus/truck or car, and fatigue riding were risk factors for having an ISS of ≥9. Age ≥ 65 years; motorcycle crashes ≥2 times in the previous year; anaemia; rural crashes; half-face helmets; protective boots; collisions with a bus/truck, car, or a stationary object; alcohol/stimulating refreshment consumption; and fatigue riding were risk factors for increased LOH. A protective factor was individuals working in commerce. Collisions with opening car doors caused low risks of having an ISS of ≥9 and a short LOH. CONCLUSION: Certain factors were significantly associated with riders' injury severity and related medical resource consumption. Because of differences in the power output, use, and riding environment, risk factors for severe injuries in LMC crashes are dissimilar from those for heavy motorcycles (cylinder capacities > 250 cc) in developed countries and deserve more attention for injury prevention. Further in-depth evaluation of significant factors based on this study's results can yield valuable information to reduce severe injuries after LMC crashes in countries and areas with a high dependency on motorcycles, even considering the popularity of electric motorcycles.

Improving the timeliness and accuracy of injury severity data in road traffic accidents in an emerging economy setting.

Road traffic injuries (RTIs) are among the leading causes of injury and fatality worldwide. RTI casualties are continually increasing in Taiwan; however, because of a lack of an advanced method for classifying RTI severity data, as well as the fragmentation of data sources, road traffic safety and health agencies encounter difficulties in analyzing RTIs and their burden on the healthcare system and national resources. These difficulties lead to blind spots during policy-making for RTI prevention and control. After compiling classifications applied in various countries, we summarized data sources for RTI severity in Taiwan, through which we identified data fragmentation. Accordingly, we proposed a practical classification for RTI severity, as well as a feasible model for collecting and integrating these data nationwide. This model can provide timely relevant data recorded by medical professionals and is valuable to healthcare providers. The proposed model's pros and cons are also compared to those of other current models.

Compressive radial neuropathy by a synovial cyst during pregnancy: A clinical case report.

RATIONALE: Compressive radial neuropathy by a synovial cyst in the radial tunnel during pregnancy is a rare occurrence. The management of radial nerve compression caused by a synovial cyst in a pregnant patient is a surgical dilemma owing to the fetal and maternal risks of treatment. PATIENT CONCERNS AND DIAGNOSIS: A 37-year-old pregnant woman presented with progressive forearm pain at the gestational age of 12 weeks. A cyst was identified via musculoskeletal ultrasound and magnetic resonance imaging examinations in the radiocapitellar joint causing radial compressive neuropathy. INTERVENTIONS: After regional nerve block and surgical removal of the cyst, the patient's forearm pain was alleviated without neurological deficits. OUTCOME: symptoms from nerve compression were improved after surgical treatment LESSONS:: This report illustrates the case of a pregnant woman presenting a compressive neuropathy by an enlarged cyst possibly due to the unbalance of growth factors during pregnancy. With proper diagnosis and timely surgical intervention, such patients can achieve good neurologic recovery without maternal or fetal complications.

A Modified Pull-out Wire Technique for Acute Mallet Fracture of the Finger.

BACKGROUND: A variety of surgical techniques for treating mallet fracture finger has been reported with different outcomes and complications. However, the optimal procedure remains controversial. This study describes surgical outcomes of mallet fractures of the finger with distal phalanx treated by modified pull-out wire fixation with Kirschner wire (K-wire) stabilization of the DIP joint in hyperextension. MATERIALS AND METHODS: 30 patients who had mallet fracture finger injuries (Doyle's classification type IVC) with DIP joint subluxation between January 2009 and January 2015 were included in this study. The mean age was 28 years (range 18-50 years), and the mean duration of followup was 8 months (range 6-12 months). Outcome assessments included the skin necrosis, wire tract infection, bony union, and extension lag. We measured the pinch strength test at 8 weeks and 12 weeks postoperatively and graded the clinical results using Crawford's criteria. RESULTS: All fractures united after surgery. There was no iatrogenic fracture fragmentation, marginal skin necrosis, wire tract infection, and nail deformity. The mean extension lag was 1.8° (range 0°-17°) through goniometer, 24 of 30 patients had 0° of extension lag. The pinch strength measured at 8 weeks and 12 weeks was 79% and improved to 91%, respectively, compared with uninjured opposite finger. According to Crawford's criteria, 24 patients were classified as excellent, 3 were good, and 3 were fair. No poor result in this study. CONCLUSION: Our modified pull-out wire fixation over a button and K-wire stabilization of DIP joint in hyperextension is a reliable surgical method for treating acute mallet fracture finger and DIP joint volar subluxation.

JNK Inactivation Induces Polyploidy and Drug-Resistance in Coronarin D-Treated Osteosarcoma Cells.

Inhibition of proliferating cells is a critical strategy for cancer therapy. In this study, we demonstrated that coronarin D, a natural component extracted from the rhizomes of Hedychium coronarium, significantly suppressed the proliferation of osteosarcoma cells. The treatment with coronarin D resulted in the activation of caspase-3 and apoptosis. This treatment induced the accumulation of cyclin B1 and DNA condensation indicating the treated osteosarcoma cells were arrested in mitotic phase. Furthermore, the treatment with coronarin D increased the levels of phosphorylated c-Jun NH2-terminal kinase (JNK) in human osteosarcoma cells. Pretreatment with JNK inhibitor blocked the accumulation of cyclin B1 and DNA condensation, resulting the accumulation of tetraploid cells in coronarin D-treated osteosarcoma HOS cells, indicating JNK inactivation blocked the mitotic entry and arrested cells in the 4 N state. After adaptation, the arrested tetraploid cells continued to duplicate their DNA resulting in polyploidy. Interestingly, when the arrested mitotic cells induced by coronarin D were treated with JNK inhibitor, the accumulated cyclin B1 and DNA condensation were immediately eliminated. These arrested 4 N cells loss the ability to undergo cytokinesis, and ultimately continued to duplicate DNA upon prolonged arrest resulting in the production of polyploid populations. JNK inactivation, either by the pretreatment with JNK inhibitor or the treatment with JNK inhibitor in coronarin D-induced mitotic cells, both caused resistance to coronarin D-induced cell death. Taken together, our findings indicate that coronarin D induces the apoptosis and mitosis arrest in human osteosarcoma cells. JNK has a crucial role in coronarin D-induced mitosis arrest and apoptosis. We hypothesize that functional evaluation of JNK may produce more specific and effective therapies in coronarin D-related trail for treatment of human osteosarcoma.

Carnosol-Induced ROS Inhibits Cell Viability of Human Osteosarcoma by Apoptosis and Autophagy.

Carnosol is an anti-oxidant and anti-inflammatory compound from rosemary. In this paper, we investigated antitumor activity of carnosol against human osteosarcoma cells. We found the viability of human osteosarcoma MG-63 cells was significantly decreased in the presence of carnosol (cell viabilities: 17.2% for 20[Formula: see text]µg/ml of CS vs. 100% for control, [Formula: see text]). Carnosol induced apoptosis and cell cycle arrest in a dose-dependent manner in MG-63 cells. Furthermore, carnosol exposure increased the levels of reactive oxygen species (ROS). The pre-treatment of NAC, the ROS scavenger, blocked the inhibition of cell viability in the carnosol treatment, indicating that ROS is important in the antiproliferation effect. Moreover, we demonstrated that carnosol significantly induced autophagy and co-administration of autophagy inhibitor reduced the antiproliferating effect of carnosol. This result exhibited the cytotoxic effect of autophagy induced by carnosol in MG-63 cells. Interestingly, the treatment of NAC decreased carnosol-induced autophagy. Collectively, these data indicate that carnosol suppresses the viability of human osteosarcoma MG-63 cells by upregulation of apoptosis and autophagy, which are both mediated by ROS. Thus, carnosol might serve as a potential therapeutic agent against osteosarcoma.

Methyl Protodioscin Induces Apoptosis in Human Osteosarcoma Cells by Caspase-Dependent and MAPK Signaling Pathways.

Methyl protodioscin (MPD), a furostanol saponin derived from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), has been shown to exhibit broad bioactivities such as anti-inflammation and antitumor activities. Here, we explored the molecular mechanisms by which MPD induced apoptosis in MG-63 cells. The data showed that MPD significantly suppressed cell growth (cell viabilities: 22.5 ± 1.9% for 8 µM MPD versus 100 ± 1.4% for control, P < 0.01) and enhanced cell apoptosis. The exposure to MPD resulted in a significant induction of reactive oxygen species, loss of mitochondrial membrane potential, and activation of caspase-9 and caspase-3 (P < 0.01, all cases). Furthermore, treatment with MPD increased the levels of phosphorylated JNK and p38 MAPK and markedly decreased the levels of phosphorylated ERK in MG-63 cells. Co-administration of the JNK-specific antagonist, the p38-specific antagonist, or the caspase antagonist (P < 0.05, all cases) has reversed the apoptotic effects in MPD treatment. We also found that exposure to MPD resulted in a significant reduction in the protein level of anti-apoptotic proteins Bcl-2, survivin, and XIAP (P < 0.05, all cases). In conclusion, our results indicate that MPD induces apoptosis of human osteosarcoma MG-63 cells, at least in part, by caspase-dependent and MAPK signaling pathways.

Combined Use of Zoledronic Acid Augments Ursolic Acid-Induced Apoptosis in Human Osteosarcoma Cells through Enhanced Oxidative Stress and Autophagy.

Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of human osteosarcoma MG-63 cells through enhanced oxidative stress and apoptosis. Interestingly, an inhibitor of osteoclast-mediated bone resorption, zoledronic acid (ZOL), also a third-generation nitrogen-containing bisphosphonate, is effective in the treatment of bone metastases in patients with various solid tumors. In this present study, we found that UA combined with ZOL to significantly suppress cell viability, colony formation, and induce apoptosis in two lines of human osteosarcoma cells. The pre-treatment of the antioxidant had reversed the oxidative stress and cell viability inhibition in the combined treatment, indicating that oxidative stress is important in the combined anti-tumor effects. Moreover, we demonstrated that ZOL combined with UA significantly induced autophagy and co-administration of autophagy inhibitor reduces the growth inhibitory effect of combined treatment. Collectively, these data shed light on the pathways involved in the combined effects of ZOL and UA that might serve as a potential therapy against osteosarcoma.

Ursolic Acid Triggers Apoptosis in Human Osteosarcoma Cells via Caspase Activation and the ERK1/2 MAPK Pathway.

Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, has been shown to trigger apoptosis in several lines of tumor cells in vitro. We found that treatment with UA suppressed the viability of human osteosarcoma MG-63 cells and induced cell cycle arrest at sub-G1 and G2/M phases. Furthermore, exposure to UA induced intracellular oxidative stress and collapse of mitochondrial membrane permeability, resulting in the subsequent activation of apoptotic caspases 8, 9, and 3 as well as PARP cleavage, and ultimately apoptosis in MG-63 cells. Moreover, protein analysis of mitogen-activated protein kinase (MAPK)-related protein expression showed an increase in activated ERK1/2, JNK, and p38 MAPK in UA-treated MG-63 cells. In addition, UA-induced apoptosis was significantly abolished in MG-63 cells that had been pretreated with inhibitors of caspase 3, 8, and 9 and ERK1/2. Furthermore, UA-treated MG-63 cells also exhibited an enhancement in Bax/Bcl-2 ratio, whereas anti-apoptotic XIAP and survivin were down-regulated. Taken together, we provide evidence demonstrating that UA mediates caspase-dependent and ERK1/2 MAPK-associated apoptosis in osteosarcoma MG-63 cells.

First Fall-Related Injuries Requiring Hospitalization Increase the Risk of Recurrent Injurious Falls: A Nationwide Cohort Study in Taiwan.

OBJECTIVES: Recurrent falls not only have risk factors different from those of single falls but also have less favorable outcomes. The aim of our study was to determine the association between the injury characteristics of a first fall and the likelihood of recurrent injurious falls in a cohort of hospitalized patients. METHODS: We designed a nationwide retrospective cohort study and selected hospitalized patients who had injurious falls between 2001 and 2010. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of recurrent injurious falls requiring hospitalization in the following year on the basis of the patients' demographic characteristics, comorbidities, and the characteristics of injuries from the first injurious fall requiring hospitalization. RESULTS: Among the 504 512 patients hospitalized for injurious falls, 19 442 experienced recurrent injurious falls requiring hospitalization. The 1-year incidence of recurrent injurious falls requiring hospitalization was 3.85%. The incidence density was the highest within the 3-month period after the first injurious fall. The risk of recurrent injurious falls among patients aged 40 to 64, 65 to 74, and ≥ 75 years increased progressively (HR: 2.11, 95% confidence interval [CI]: 1.90-2.34; HR: 2.80, 95% CI: 2.51-3.11; and HR: 3.80, 95% CI: 3.42-4.23, respectively). The length of hospitalization (LOH) ≥ 15 or ≥ 31 days (HR: 1.39, 95% CI: 1.30-1.48; and HR: 1.59, 95% CI: 1.43-1.77, respectively) and injury to the head (HR: 1.59, 95% CI: 1.53-1.65) or spine (HR: 1.66, 95% CI: 1.59-1.74) were also found to be major risk factors. CONCLUSIONS: Our findings show that the LOH and head and spine injuries are associated with an increased risk of recurrent injurious falls leading to hospitalization. The risk of recurrent injurious falls requiring hospitalization increased significantly among adults older than 40 years. We suggest further research on the effects of injury characteristics associated with the first injurious fall requiring hospitalization and resultant anatomical damages on the risk of recurrent injurious falls requiring hospitalization. High-risk patients should receive tailored rehabilitation addressing their respective injuries within 3 months after hospital discharge.

Dodecyl gallate induces apoptosis by upregulating the caspase-dependent apoptotic pathway and inhibiting the expression of anti-apoptotic Bcl-2 family proteins in human osteosarcoma cells.

Dodecyl gallate (DG) is a gallic acid ester that has been shown to inhibit tumor growth. The aim of this study was to investigate the mechanism by which DG induces antiproliferative and apoptotic effects in MG-63 human osteosarcoma cells. Dose- and time-dependent cytotoxic effects of DG were determined using an MTT assay. The results showed that the half-maximal inhibitory concentration (IC50) of DG in MG-63 cells was 31.15 µM at 24 h, 10.66 µM at 48 h, and 9.06 µM at 72 h. Flow cytometric analysis demonstrated that exposure to 20 and 40 µM DG resulted in an increase in the sub-G1 phase population and in S-phase cell cycle arrest. Furthermore, western blot analysis of apoptosis-related protein expression revealed an increase in the activation of caspases 8 and 3, cleavage of poly (ADPribose) polymerase (PARP), and disruption of mitochondrial membrane permeability was measured by flow cytometry. An increase in the Bax/Bcl-2 ratio and a decrease in the expression of inhibitor of apoptosis protein (IAP) family members, namely X-linked inhibitor of apoptosis protein and survivin, were also observed following DG treatment. These data provide insight into the molecular mechanisms governing the ability of DG to induce apoptosis in human osteosarcoma cells in vitro.