[The Effects of the Question Prompt List on Usefulness, Satisfaction and Anxiety in Patients With Terminal Cancer: A Meta-Analysis].

BACKGROUND: Difficulties and anxiety caused by poor communication between patients with terminal cancer and their caregivers and medical teams are common in clinical practice. This may lead to uncertainty and fear of treatment, affecting the progress of treatment and achievement of hospice-care goals. The results of prior research indicate that using a question prompt list to promote shared decision-making can improve communication between medical care providers and patients. PURPOSE: This study was developed to explore the effectiveness of using question prompt lists in communications with terminal cancer patients and their families in clinical settings in Taiwan. METHODS: A systematic review of the literature using a meta-analysis research design was conducted in this study. Cochrane Risk of Bias Tool 2 was used to assess literature quality. The selected keywords were used to search six databases, including the English-language PubMed, Cochrane Library, Embase, EBSCOhost, and MEDLINE databases and the Chinese-language Airiti Library database. RevMen 5.4 software (the latest version released by the Nordic Cochrane Center in September 2020) was used for data analysis. RESULTS: Applying the question prompt list was found to significantly increase the number of questions asked (MD = 2.45, p = .01) and the usefulness (SMD = 0.25, p = .02). However, no significant changes in consultation time (MD = 4.49, p = .11), satisfaction (MD = 0.08, p = .91), or anxiety (SMD = 0.06, p = .62) were found. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results support that simplifying and focusing the topics of each chapter and theme of the question prompt list based on time of use may allow the list to be used effectively in combination with family meetings in clinical practice and to be focused based on patient, caregiver, and family needs to facilitate more-productive discussions. This will allow meetings to better facilitate therapeutic relationships and patient and caregiver participation in treatment plans. An external communication coach may be added in the future to help patients and caregivers clarify needs and concerns and improve the effectiveness of consultations. As questioning skills are important to empowering patients, a question prompt list for patients with terminal cancer should be developed. The results of this study may be used to guide the practice of healthcare providers and referenced in caregiver in-service education.

Effects of Mobile Application Program (App)-Assisted Health Education on Preventive Behaviors and Cancer Literacy among Women with Cervical Intraepithelial Neoplasia.

OBJECTIVE: This study aimed (1) to study the effects of health education on preventive behaviors and cancer literacy among women with cervical intraepithelial neoplasia (CIN); (2) to compare the effects of mobile application program (App)-assisted health education with traditional book-form health education. PARTICIPANTS: A total of 132 women ages 20 to 69 years women. METHODS: This prospective longitudinal study enrolled 132 CIN women who were evaluated three times. Propensity score matching was used by controlling subjects' age strata, body mass index, education level, occupation, and type of surgery. RESULTS: The influences of various educational tools were investigated. Four domains were assessed, including health behavior, attitude towards behavior change, self-efficacy of behavior, and cervical cancer (CCa) literacy. Significant improvements in behavior change and CCa literacy due to a health education program were observed (p ≤ 0.002). The App combined with a traditional booklet had the highest score for behavior change and was significantly greater than the booklet-only learning (p = 0.002). The App-assisted form, either App alone or combined with booklet, had a significantly better impact on health promotion when compared to the booklet alone (p = 0.045 and 0.005, respectively). App-only learning had the highest score of CCa literacy (p = 0.004). CONCLUSION: Health education interventions can have positive effects in terms of change of behavior and CCa literacy. App-assisted learning could be used as a supportive technology, and App learning alone or combined with a traditional booklet may be an innovative model of clinical health promotion for women with CIN.

Prescription Patterns of Wu Lin San Concentrated Extract Product for Cystitis in Taiwan: A Population-Based Study.

The indications for the concentrated extract product (CEP) of Wu Lin San (WLS) are urethritis, cystitis, and gonorrhea. In clinical settings, WLS is combined with other CEPs used. However, there are no prescribed guidelines of CEPs in Taiwan. In this study, we would establish the CEP-prescribed applications of WLS for cystitis according to the clinical prescription patterns and ancient traditional medicine books. The prescription patterns of WLS were analyzed from the National Health Insurance Research Database of Taiwan for the period from 2000 to 2015. The results show that WLS was most frequently prescribed for cystitis (17.12% of a total prescriptions), and its prescribed dosage was 3∼5 g per day. Among them, 62.53% were for patients >40 years, and 72.45% were for women. Moreover, prescription patterns of WLS for cystitis were divided into 4 types: Type 1, WLS combined with Pa Cheng San (PCS) and Ti Tang Tang (29.75%); Type 2, WLS combined with PCS and dandelion (13.89%); Type 3, WLS combined with PCS and Tao Ho Cheng Chi Tang (6.63%); and Type 4, WLS combined with PCS (2.75%). According to lectures, review revealed the following principles of WLS application. WLS only should be adopted for simple heat strangury, while Type 4 should be applied for excess heat and dampness strangury. For patients with heat strangury coupled with an early-stage blood amassment pattern in lower jiao (abdomen), Type 3 could be administered. Type 2 should be used for heat strangury accompanied by dampness toxicity with infection. By contrast, Type 1 should be applied to patients with severe blood stasis. The application principles of WLS with other CEPs could serve as a reference for cystitis treatment in clinical settings.

Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrPC signaling.

Forkhead box protein C1 (FOXC1) is known to regulate developmental processes in the skull and brain. Methods: The unique multipotent arachnoid-pia stem cells (APSCs) isolated from human and mouse arachnoid-pia membranes of meninges were grown as 3D spheres and displayed a capacity for self-renewal. Additionally, APSCs also expressed the surface antigens as mesenchymal stem cells. By applying the FOXC1 knockout mice and mouse brain explants, signaling cascade of FOXC1-STI-1-PrPC was investigated to demonstrate the molecular regulatory pathway for APSCs self-renewal. Moreover, APSCs implantation in stroke model was also verified whether neurogenic property of APSCs could repair the ischemic insult of the stroke brain. Results: Activated FOXC1 regulated the proliferation of APSCs in a cell cycle-dependent manner, whereas FOXC1-mediated APSCs self-renewal was abolished in FOXC1 knockout mice (FOXC1-/- mice). Moreover, upregulation of STI-1 regulated by FOXC1 enhanced cell survival and self-renewal of APSCs through autocrine signaling of cellular prion protein (PrPC). Mouse brain explants STI-1 rescues the cortical phenotype in vitro and induces neurogenesis in the FOXC1-/- mouse brain. Furthermore, administration of APSCs in ischemic brain restored the neuroglial microenvironment and improved neurological dysfunction. Conclusion: We identified a novel role for FOXC1 in the direct regulation of the STI-1-PrPC signaling pathway to promote cell proliferation and self-renewal of APSCs.

In Vitro and In Vivo Anti-Osteoarthritis Effects of 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-Glucoside from Polygonum Multiflorum.

Polygonum multiflorum Thunb. is a traditional herbal medicine that is rich in polyphenols. The major compound, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside (THSG) has many pharmacological activities, such as antioxidative and free radical-scavenging properties, and the abilities to reduce hyperlipidemia, prevent lipid peroxidation, and protect the cardiovascular system. In this study, the anti-osteoarthritis (OA) effects of THSG were explored using in vitro and in vivo models. THSG inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production and inducible NO synthase (iNOS) and cyclooxygenase-2 expressions by lipopolysaccharide-stimulated RAW 264.7 cells. On the other hand, THSG inhibited PGE2 production and iNOS and matrix metalloproteinase-13 expressions by interleukin-1ß-stimulated primary rat chondrocytes. Through a mono-iodoacetate-induced rat OA model assay, THSG reduced paw edema and improved the weight-bearing distribution. Therefore, THSG has anti-inflammatory activity and could be applied as a lead compound for the development as an OA drug.

The incidence and factors of hip fractures and subsequent morbidity in Taiwan: An 11-year population-based cohort study.

Hip fractures are a major problem to elder population, but subsequent morbidity is unclear about environmental factors and socioeconomic conditions. The study aims to investigate the incidence of hip fractures treated by the surgery; to compare the sequelae and temporal trends of hip fractures; to evaluate the seasonal effects in the subsequent short-term and long-term morbidities after hip fractures. A cohort study design is conducted using national health research datasets between 2000 and 2010. The ICD-9-CM diagnostic codes were utilized to investigate the incidence of hip fractures and the corresponding treatments. Hierarchical modeling was used to analyze the factors associated with various types of hip fractures. The results indicated that females had a lower incidence in the 30-44 age group, but a significantly higher incidence than males among those aged 60 years or older (adjusted rates 232.1 vs. 100.3 per 100,000 persons, p<0.001). The incidence of hip fractures in the low-income group showed no significant difference compared to that in the general population. There was a temporal trend of a 8.6% increase in the incidence of all types of hip fractures over the period of 2000-2010. A summer-winter variation is observed among the elderly. Hip fractures and subsequent morbidity are increasing in Taiwan's aging society. Older age, female gender, and time periods were independent risk factors for subsequent morbidities after surgical treatment. The result of this study is useful to the healthcare policy makers and to raise the public awareness of hip fractures.

Tumor-associated NADH oxidase (tNOX)-NAD+-sirtuin 1 axis contributes to oxaliplatin-induced apoptosis of gastric cancer cells.

Oxaliplatin belongs to the platinum-based drug family and has shown promise in cancer treatment. The major mechanism of action of platinum compounds is to form platinum-DNA adducts, leading to DNA damage and apoptosis. Accumulating evidence suggests that they might also target non-DNA molecules for their apoptotic activity. We explored the effects of oxaliplatin on a tumor-associated NADH oxidase (tNOX) in gastric cancer lines. In AGS cells, we found that the oxaliplatin-inhibited tNOX effectively attenuated the NAD+/NADH ratio and reduced the deacetylase activity of an NAD+-dependent sirtuin 1, thereby enhancing p53 acetylation and apoptosis. Similar results were also observed in tNOX-knockdown AGS cells. In the more aggressive MKN45 and TMK-1 lines, oxaliplatin did not inhibit tNOX, and induced only minimal apoptosis and cytotoxicity. However, the downregulation of either sirtuin 1 or tNOX sensitized TMK-1 cells to oxaliplatin-induced apoptosis. Moreover, tNOX-depletion in these resistant cells enhanced spontaneous apoptosis, reduced cyclin D expression and prolonged the cell cycle, resulting in diminished cancer cell growth. Together, our results demonstrate that oxaliplatin targets tNOX and SIRT1, and that the tNOX-NAD+-sirtuin 1 axis is essential for oxaliplatin-induced apoptosis.

Retrospective one-million-subject fixed-cohort survey of utilization of emergency departments due to traumatic causes in Taiwan, 2001-2010.

BACKGROUND: Epidemiological study was needed to evaluate trends in emergency department (ED) utilization that could be taken into account when making policy decisions regarding the delivery and distribution of medical resources. METHODS: A retrospective fixed-cohort study of emergency medical utilization from 2001 to 2010 was performed based on one-million people sampled in 2010 in Taiwan. Focusing on traumatic cases, the annual incidences in various groups split according to sex and age were calculated, and further information regarding location of trauma and type of trauma was obtained. RESULTS: In 2010, significantly greater proportions of male and younger subjects were visitors to EDs with a traumatic injury. During 2001-2010, the number of both traumatic cases and non-traumatic cases presenting at EDs significantly increased (average annual percentage change, AAPC 4.7 and 3.6, respectively) and a significantly greater direct medical cost associated with traumatic cases than non-traumatic cases was noted. Focusing on traumatic cases, most of these cases were directed to highest-level hospitals, accounting for 73.5-78.8 % of all traumatic cases, with a significant AAPC of 5.6. The traumatic ED visit annual incidence in males was 58.63 in 2001, which significantly increased to 69.35 per 1000 persons in 2010 (AAPC 1.5); and in females was 38.96 in 2001, which significantly increased to 50.73 per 1000 persons in 2010 (AAPC 2.5). Most of the traumatic cases treated in EDs were minor injuries, such as contusion with the skin intact, open wound of the upper limbs, open wound of the head, neck, or trunk, and other superficial injury (accounting for about 60 % of all cases). The traumatic categories of sprains/strains of joints and adjacent muscles, fractures of upper limbs, fractures of lower limbs, and fractures of the spine/trunk required greater medical resources and significantly positive AAPC values (4.3, 4.0, 4.5 and 6.8, respectively). CONCLUSIONS: Increased ED utilization due to traumatic causes, as assessed by the annual number of cases and incidence, average direct medical cost and highest-level hospital utilization, was observed from 2001 to 2010. Orthopedic-related injuries, including soft tissue trauma of extremities and various fractures, were the categories with the greatest increase in incidence.

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1).

Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.

Capsaicin Inhibited Aggressive Phenotypes through Downregulation of Tumor-Associated NADH Oxidase (tNOX) by POU Domain Transcription Factor POU3F2.

Capsaicin has been reported to preferentially inhibit the activity of tumor-associated NADH oxidase (tNOX), which belongs to a family of growth-related plasma membrane hydroquinone oxidases in cancer/transformed cells. The inhibitory effect of capsaicin on tNOX is associated with cell growth attenuation and apoptosis. However, no previous study has examined the transcriptional regulation of tNOX protein expression. Bioinformatic analysis has indicated that the tNOX promoter sequence harbors a binding motif for POU3F2, which is thought to play important roles in neuronal differentiation, melanocytes growth/differentiation and tumorigenesis. In this study, we found that capsaicin-mediated tNOX downregulation and cell migration inhibition were through POU3F2. The protein expression levels of POU3F2 and tNOX are positively correlated, and that overexpression of POU3F2 (and the corresponding upregulation of tNOX) enhanced the proliferation, migration and invasion in AGS (human gastric carcinoma) cells. In contrast, knockdown of POU3F2 downregulates tNOX, and the cancer phenotypes are affected. These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis.

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.

Update on a tumor-associated NADH oxidase in gastric cancer cell growth.

Gastric cancer is one of the most common human malignancies, and its prevalence has been shown to be well-correlated with cancer-related deaths worldwide. Regrettably, the poor prognosis of this disease is mainly due to its late diagnosis at advanced stages after the cancer has already metastasized. Recent research has emphasized the identification of cancer biomarkers in the hope of diagnosing cancer early and designing targeted therapies to reverse cancer progression. One member of a family of growth-related nicotinamide adenine dinucleotide (NADH or hydroquinone) oxidases is tumor-associated NADH oxidase (tNOX; ENOX2). Unlike its counterpart CNOX (ENOX1), identified in normal rat liver plasma membranes and shown to be stimulated by growth factors and hormones, tNOX activity purified from rat hepatoma cells is constitutively active. Its activity is detectable in the sera of cancer patients but not in those of healthy volunteers, suggesting its clinical relevance. Interestingly, tNOX expression was shown to be present in an array of cancer cell lines. More importantly, inhibition of tNOX was well correlated with reduced cancer cell growth and induction of apoptosis. RNA interference targeting tNOX expression in cancer cells effectively restored non-cancerous phenotypes, further supporting the vital role of tNOX in cancer cells. Here, we review the regulatory role of tNOX in gastric cancer cell growth.

A Review of Barriers to Minorities' Participation in Cancer Clinical Trials: Implications for Future Cancer Research.

To enhance nurses' awareness and competencies in practice and research by reporting the common barriers to participation of minorities in cancer clinical trials and discussing facilitators and useful strategies for recruitment. Several databases were searched for articles published in peer reviewed journals. Some of the barriers to minorities' participation in clinical trials were identified within the cultural social-context of cancer patients. The involvement of community networking was suggested as the most effective strategy for the recruitment of minorities in cancer clinical trials. Using culturally sensitive approaches to enhance ethnic minorities' participation is important for advancing cancer care and eliminating health disparities. Awareness of barriers and potential facilitators to the enrollment of ethnic minority cancer patients may contribute to enhancing nurses' competencies of recruiting ethnic minorities in nursing research, playing efficient roles in cancer clinical trials team, and providing culturally competent quality care.

Synthesis and Characterization of 4,11-Diaminoanthra[2,3-b]furan-5,10-diones: Tumor Cell Apoptosis through tNOX-Modulated NAD(+)/NADH Ratio and SIRT1.

A series of new 4,11-diaminoanthra[2,3-b]furan-5,10-dione derivatives with different side chains were synthesized. Selected 2-unsubstituted derivatives 11-14 showed high antiproliferative potency on a panel of mammalian tumor cell lines including multidrug resistance variants. Compounds 11-14 utilized multiple mechanisms of cytotoxicity including inhibition of Top1/Top2-mediated DNA relaxation, reduced NAD(+)/NADH ratio through tNOX inhibition, suppression of a NAD(+)-dependent sirtuin 1 (SIRT1) deacetylase activity, and activation of caspase-mediated apoptosis. Here, for the first time, we report that tumor-associated NADH oxidase (tNOX) and SIRT1 are important cellular targets of antitumor anthracene-9,10-diones.

Sirtuin 1 (SIRT1) Deacetylase Activity and NAD⁺/NADH Ratio Are Imperative for Capsaicin-Mediated Programmed Cell Death.

Capsaicin is considered a chemopreventive agent by virtue of its selective antigrowth activity, commonly associated with apoptosis, against cancer cells. However, noncancerous cells possess relatively higher tolerance to capsaicin, although the underlying mechanism for this difference remains unclear. Hence, this study aimed to elucidate the differential effects of capsaicin on cell lines from lung tissues by addressing the signal pathway leading to two types of cell death. In MRC-5 human fetal lung cells, capsaicin augmented silent mating type information regulation 1 (SIRT1) deacetylase activity and the intracellular NAD(+)/NADH ratio, decreasing acetylation of p53 and inducing autophagy. In contrast, capsaicin decreased the intracellular NAD(+)/NADH ratio, possibly through inhibition of tumor-associated NADH oxidase (tNOX), and diminished SIRT1 expression leading to enhanced p53 acetylation and apoptosis. Moreover, SIRT1 depletion by RNA interference attenuated capsaicin-induced apoptosis in A549 cancer cells and autophagy in MRC-5 cells, suggesting a vital role for SIRT1 in capsaicin-mediated cell death. Collectively, these data not only explain the differential cytotoxicity of capsaicin but shed light on the distinct cellular responses to capsaicin in cancerous and noncancerous cell lines.

Emergency visits among end-of-life cancer patients in Taiwan: a nationwide population-based study.

BACKGROUND: An increased number of emergency visits at the end of life may indicate poor-quality cancer care. The study aimed to investigate the prevalence and utilization of emergency visits and to explore the reasons for emergency department (ED) visits among cancer patients at the end of life. METHODS: A retrospective cohort study was performed by tracking one year of ambulatory medical service records before death. Data were collected from the cancer dataset of Taiwan's National Health Insurance Research Database (NHIRD). RESULTS: A total of 32,772 (19.2%) patients with malignant cancer visited EDs, and 23,883 patients died during the study period. Of these, the prevalence of emergency visits in the mortality group was 81.5%, and their ED utilization was significantly increased monthly to the end of life. The most frequent types of cancer were digestive and peritoneum cancers (34.8%), followed by breast cancer (17.7%) and head and neck cancers (13.3%). Older patients, males, and those diagnosed with metastases, respiratory or digestive cancer were more likely to use ED services at the end of life. Use of an ED service in the nearest community hospital to replace medical centers for dying cancer patients would be more acceptable in emergency situations. CONCLUSIONS: Our study provided population-based evidence related to ED utilization. An understanding of the reasons for such visits could be useful in preventing overuse of ED visits to improve the quality of end-of-life care.

Epidemiology of hospitalized traumatic pelvic fractures and their combined injuries in Taiwan: 2000-2011 National Health Insurance data surveillance.

BACKGROUND: From the viewpoint of prehospital emergency medicine, a greater proportion of pelvic fractures not of a life-threatening status but combined with other injuries need more comprehensive recognition. METHODS: A 12-year nationwide health database of inpatients was reviewed. All cases diagnosed as pelvic fractures were enrolled. The associated injuries classified into 20 categories were further analyzed. RESULTS: During 2000-2011, the hospitalized incidence of pelvic fractures in Taiwan ranged from 17.17 to 19.42 per 100,000, and an increasing trend with age was observed. The mean case-fatality rate was 1.6% for females and 2.1% for males; male patients with pelvic fractures had a significantly higher risk of death than female patients after adjusting for other covariates. 74.2% of these cases were combined with other injuries. The most common associated injuries in an identified body region were other orthopedic fractures of the lower limbs (21.50%), spine/trunk (20.97%), or upper limbs (18.18%), followed by significant head injuries (17.59%), intra-abdominal injuries (11.00%), and thoracic injuries (7.20%). CONCLUSION: The incidence of hospitalized pelvic fractures in Taiwan was low and the case-fatality rate was lower than those of other countries. Concurrently, coexistence of major combined injuries with pelvic fractures was easily treated at medical centers.

Extensive evaluations of the cytotoxic effects of gold nanoparticles.

BACKGROUND: Many in vitro studies have revealed that the interference of dye molecules in traditional nanoparticle cytotoxicity assays results in controversial conclusions. The aim of this study is to establish an extensive and systematic method for evaluating biological effects of gold nanoparticles in mammalian cell lines. METHODS: We establish the cell-impedance measurement system, a label-free, real-time cell monitoring platform that measures electrical impedance, displaying results as cell index values, in a variety of mammalian cell lines. Cytotoxic effects of gold nanoparticles are also evaluated with traditional in vitro assays. RESULTS: Among the six cell lines, gold nanoparticles induce a dose-dependent suppression of cell growth with different levels of severity and the suppressive effect of gold nanoparticles was indirectly associated with their sizes and cellular uptake. Mechanistic studies revealed that the action of gold nanoparticles is mediated by apoptosis induction or cell cycle delay, depending on cell type and cellular context. Although redox signaling is often linked to the toxicity of nanoparticles, in this study, we found that gold nanoparticle-mediated reactive oxygen species generation was not sustained to notably modulate proteins involved in antioxidative defense system. CONCLUSION: The cell-impedance measurement system, a dye-free, real-time screening platform, provides a reliable analysis for monitoring gold nanoparticle cytotoxicity in a variety of mammalian cell lines. Furthermore, gold nanoparticles induce cellular signaling and several sets of gene expression to modulate cellular physical processes. GENERAL SIGNIFICANCE: The systematic approach, such as cell-impedance measurement, analyzing the toxicology of nanomaterials offers convincing evidence of the cytotoxicity of gold nanomaterials.

Epidemiological survey of orthopedic joint dislocations based on nationwide insurance data in Taiwan, 2000-2005.

BACKGROUND: The epidemiology of acute orthopedic dislocations is poorly understood. A nationwide database provides a valuable resource for examining this issue in the Taiwanese population. METHODS: A 6-year retrospective cohort study of 1,000,000 randomly-sampled beneficiaries from the year 2005 was used as the original population. Based on the hospitalized and ambulatory data, the concomitant ICD9-CM diagnosis codes and treatment codes were evaluated and classified into 8 and 3 major categories, respectively. The cases matching both inclusive criteria of dislocation-related diagnosis codes and treatment codes were defined as incident cases. RESULTS: During 2000-2005, the estimated annual incidence (per 100,000 population) of total orthopedic dislocations in Taiwan was 42.1 (95%CI: 38.1-46.1). The major cause of these orthopedic dislocations was traffic accidents (57.4%), followed by accident falls (27.5%). The annual incidence dislocation by location was shoulder, 15.3; elbow, 7.7; wrist, 3.5; finger, 4.6; hip, 5.2; knee, 1.4; ankle, 2.0; and foot, 2.4. Approximately 16% of shoulder dislocations occurred with other concomitant fractures, compared with 17%, 53%, 16%, 76% and 52%, respectively, of dislocated elbow, wrist, hip, knee, and ankle cases. Including both simple and complex dislocated cases, the mean medical cost was US$612 for treatment of a shoulder dislocation, $504 for the elbow, $1,232 for the wrist, $1,103 for the hip, $1,888 for the knee, and $1,248 for the ankle. CONCLUSIONS: In Taiwan, three-quarters of all orthopedic dislocations were of the upper limbs. The most common complex fracture-dislocation was of the knee, followed by the wrist and the ankle. Those usually needed a treatment combined with open reduction of fractures and resulted in a higher direct medical expenditure.