Search

ObjectiveThis meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety.MethodsSeveral major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods.ResultsSeven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17-0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10-1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: -2.94s, 95%CI: -10.28-4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time.ConclusionThe use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion.

Objective: This meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety. Methods: Several major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods. Results: Seven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17–0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10–1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: −2.94s, 95%CI: −10.28–4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time. Conclusion: The use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion. [ABSTRACT FROM AUTHOR]

COVID-19 arrived in the United States in early 2020, with cases quickly being reported in many states including Pennsylvania. Many statistical models have been proposed to understand the trends of the COVID-19 pandemic and factors associated with increasing cases. While Poisson regression is a natural choice to model case counts, this approach fails to account for correlation due to spatial locations. Being a contagious disease and often spreading through community infections, the number of COVID-19 cases are inevitably spatially correlated as locations neighboring counties with a high COVID-19 case count are more likely to have a high case count. In this analysis, we combine generalized estimating equations (GEEs) for Poisson regression, a popular method for analyzing correlated data, with a semivariogram to model daily COVID-19 case counts in 67 Pennsylvania counties between March 20, 2020 to January 23, 2021 in order to study infection dynamics during the beginning of the pandemic. We use a semivariogram that describes the spatial correlation as a function of the distance between two counties as the working correlation. We further incorporate a zero-inflated model in our spatial GEE to accommodate excess zeros in reported cases due to logistical challenges associated with disease monitoring. By modeling time-varying holiday covariates, we estimated the effect of holiday timing on case count. Our analysis showed that the incidence rate ratio was significantly greater than one, 6-8 days after a holiday suggesting a surge in COVID-19 cases approximately one week after a holiday.

Introduction Individuals with special health care needs continue to experience difficulties with accessing regular dental care. This has largely been due to clinicians feeling they lack the training and experience to manage their needs. The aim of this study was to determine whether working closely with specialists in special need dentistry influenced the willingness of clinicians to treat patients with special needs. Materials and methods Semi-structured interviews were conducted with specialists and clinicians involved in these mentoring initiatives. Qualitative thematic analysis was used to determine perspectives towards how this additional support influenced their willingness to treat individuals with special needs. Results The views of all participants towards these supports were positive with clinicians feeling it not only offered them opportunities to learn from the specialists, but also increased their willingness to treat individuals with special needs and the timeliness and quality of care they were able to provide. Likewise, despite some concerns about the inappropriate use of specialist support, the specialists felt these mentoring relationships offered many benefits including improving timely access to care and ensuring individuals were able to receive appropriate care. Conclusions Mentoring provided by specialists in special needs dentistry improved the willingness of clinicians to provide care for individuals with special health care needs. Supports such as these are likely to be crucial to overcoming concerns of clinicians about their ability to manage the needs of these individuals and begin to address a significant barrier to access of care for individuals with special health care needs.

ObjectivesThis study establishes age- and sex-specific reference values for fat mass index (FMI), lean mass index (LMI), appendicular LMI (aLMI), and body fat distribution indices including Android/Gynoid % fat ratio and Trunk/Limb % fat ratio in multi-ethnic Singaporean adults.MethodsA population-based cross-sectional study using dual-energy X-ray absorptiometry (Hologic Discovery Wi) was carried out to measure whole body and regional fat and lean mass in community-dwelling adults. A total of 537 adults (57.5% women), aged from 21 to 90 years, were recruited from the large north-eastern residential town of Yishun. Age- and sex-specific percentile reference values were generated for FMI, LMI, aLMI, Android/Gynoid % fat ratio and Trunk/Limb % fat ratio using the Lambda-Mu-Sigma method. The relationship between the parameters and age were assessed through the Pearson's correlation coefficient.ResultsAll parameters demonstrated significant correlation with age (p < 0.05) for both men and women, except for LMI in women, with the strength of r ranging from 0.12 (weak correlation) to 0.54 (strong correlation). LMI (r = -0.45) and appendicular LMI (r = -0.54) were negatively associated with age in men while none (r = -0.06) to weak correlation (r = -0.14) were shown in women for the same parameters respectively. The Android/Gynoid % fat ratio and Trunk/Limb % fat ratio were positively related to age for both men (r = 0.37 & 0.43, p < 0.001) and women (r = 0.52 & 0.48, p < 0.001).ConclusionWe have established DXA-based body composition reference data for the Singapore adult population. These reference data will be particularly useful in geriatric, obesity and oncology clinics, enabling the prescription of appropriate therapy to individuals at risk of morbidity from unfavorable body composition phenotypes. It also adds on to the limited reference database on Southeast Asian body composition.

As the most common type of neurodegenerative diseases (NDDs), Alzheimer's disease (AD) is thought to be caused mainly by the excessive aggregation of β-amyloid protein (Aβ). However, a growing number of studies have found that reactive oxygen species (ROS) play a key role in the onset and progression of AD. The present study aimed to probe the neuroprotective effect of high-frequency low-intensity pulsed electric field (H-LIPEF) for SH-SY5Y cells against hydrogen peroxide (H2O2) and Aβ-induced cytotoxicity. By looking in a systematic way into the frequency- and amplitude-dependent neuroprotective effect of pulsed electric field (PEF), the study finds that H-LIPEF at 200 Hz produces the optimal protective effect for SH-SY5Y cells. The underlying mechanisms were confirmed to be due to the activation of extracellular signal-regulated kinase (ERK) pathway and the downstream prosurvival and antioxidant proteins. Because the electric field can be modified to focus on specific area in a non-contact manner, the study suggests that H-LIPEF holds great potential for treating NDDs, whose effect can be further augmented with the administering of drugs or natural compounds at the same time.

This experimental study aimed to compare the internal fit (marginal fit and internal discrepancy) of metal crowns fabricated by traditional casting and digital methods (computer numerically controlled (CNC) milling and three-dimensional [3D] printing). Thirty standard master abutment models were fabricated using a 3D printing technique with digital software. Metal crowns were fabricated by traditional casting, CNC milling, and 3D printing. The silicon replica method was used to measure the marginal and internal fit. A thin layer of low-viscosity polyvinyl siloxane material was placed inside each crown and on the die (like a seat) until the material was set. Replicas were examined at four reference points under a microscope: the central pit (M1), cusp tip (M2), axial wall (M3), and margin (M4). The measured data were analyzed using a one-way analysis of variance (ANOVA) to verify statistical significance, which was set at p < 0.05. In the traditional casting group, the minimum distance measured was at M3 (90.68 ± 14.4 μm) and the maximum distance measured was at M1 (145.12 ± 22 μm). In the milling group, the minimum distance measured was at M3 (71.85 ± 23.69 μm) and the maximum distance measured was at M1 (108.68 ± 10.52 μm). In the 3D printing group, the minimum distance measured was at M3 (100.59 ± 9.26 μm) and the maximum distance measured was at M1 (122.33 ± 7.66 μm). The mean discrepancy for the traditional casting, CNC milling, and 3D printing groups was 120.20, 92.15, and 111.85 μm, respectively, showing significant differences (P < 0.05). All three methods of metal crown fabrication, that is, traditional casting, CNC milling, and 3D printing, had values within the clinically acceptable range. The marginal and internal fit of the crown was far superior in the CNC milling method.

In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p

BackgroundSarcopenia and obesity are reportedly associated with risk of cognitive decline, and sarcopenic obesity (SO) heightens the risk, but the evidence is sparse and inconclusive. This study aimed to examine the association between SO and cognitive impairment.MethodsA total of 542 community-dwelling adults aged between 21 and 90 years were recruited. All participants were assessed for body composition (dual X-ray absorptiometry), handgrip strength (HGS), gait speed (GS), and cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status). Sarcopenia was defined by the presence of low appendicular lean mass index (ALMI) and low HGS or low GS according to the 2019 Asian Working Group for Sarcopenia criteria, and obesity was defined based on the upper two quintiles of fat mass index (FMI).ResultsSarcopenia alone or in combination with obesity were not significantly associated with cognitive impairment after controlling for confounding variables. Obesity on its own was significantly associated with greater odds of impaired attention (OR: 2.05, 95%CI 1.12-3.82). Low ALMI was not associated, but low HGS, slow GS, and high FMI were individually associated with cognitive impairment: low HGS and immediate memory (OR: 1.91, 95% CI 1.04-3.49); low GS and immediate memory (OR: 2.17, 95% CI 1.26-3.72); high FMI and attention (OR: 2.06, 95% CI 1.22-3.51). Co-occurring high FMI with either low HGS or slow GS exacerbated the observed odds of global and domain-specific (attention, visuospatial) cognitive impairment.ConclusionsLean mass is not relevant, whereas muscle strength and physical performance or adiposity are relevant in defining sarcopenia or sarcopenic obesity in terms of their cognitive impacts.

BackgroundThe U.S. has experienced an unprecedented number of orders to shelter in place throughout the ongoing COVID-19 pandemic. We aimed to ascertain whether social distancing; difficulty with daily activities; and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of the nation's first shelter-in-place orders (SIPO) among individuals living in the seven affected counties in the San Francisco Bay Area.MethodsWe conducted an online, cross-sectional social media survey from March 14 -April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area versus elsewhere in the U.S.ResultsIn this non-representative sample, the percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty obtaining hand sanitizer, medications, and in particular respondents reported increased difficulty obtaining food in the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the announcement.ConclusionThis study characterizes early changes in attitudes, behaviors, and difficulties. As states and localities implement, rollback, and reinstate shelter-in-place orders, ongoing efforts to more fully examine the social, economic, and health impacts of COVID-19, especially among vulnerable populations, are urgently needed.

Most existing cancer treatments involve high-cost chemotherapy and radiotherapy, with major side effects, prompting effort to develop alternative treatment modalities. It was reported that the combination of thermal-cycling hyperthermia (TC-HT) and phenolic compound exhibited a moderate cytotoxic effect against human pancreatic cancer PANC-1 cells. In this study, we investigate the efficacy of triple combination in PANC-1 cancer cells by adopting low-intensity pulsed electric field (LIPEF) to couple with TC-HT and CGA (chlorogenic acid). The study finds that this triple combination can significantly impede the proliferation of PANC-1 cells, with only about 20% viable cells left after 24h, whereas being non-toxic to normal cells. The synergistic activity against the PANC-1 cells was achieved by inducing G2/M phase arrest and apoptosis, which were associated with up-regulation of p53 and coupled with increased expression of downstream proteins p21 and Bax. Further mechanism investigations revealed that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by the reduced level of Bcl-2, mitochondrial dysfunction, and sequential activation of caspase-9 and PARP. Also, we found that the triple treatment led to the increase of intracellular reactive oxygen species (ROS) production. Notably, the triple treatment-induced cytotoxic effects and the elevated expression of p53 and p21 proteins as well as the increased Bax/Bcl-2 ratio, all could be alleviated by the ROS scavenger, N-acetyl-cysteine (NAC). These findings indicate that the combination of CGA, TC-HT, and LIPEF may be a promising modality for cancer treatment, as it can induce p53-dependent cell cycle arrest and apoptosis through accumulation of ROS in PANC-1 cells.

Neurodegenerative diseases (NDDs) are becoming a major threat to public health, according to the World Health Organization (WHO). The most common form of NDDs is Alzheimer's disease (AD), boasting 60-70% share. Although some debates still exist, excessive aggregation of β-amyloid protein (Aβ) and neurofibrillary tangles has been deemed one of the major causes for the pathogenesis of AD. A growing number of evidences from studies, however, have suggested that reactive oxygen species (ROS) also play a key role in the onset and progression of AD. Although scientists have had some understanding of the pathogenesis of AD, the disease still cannot be cured, with existing treatment only capable of providing a temporary relief at best, partly due to the obstacle of blood-brain barrier (BBB). The study was aimed to ascertain the neuroprotective effect of thermal cycle hyperthermia (TC-HT) against hydrogen peroxide (H2O2) and Aβ-induced cytotoxicity in SH-SY5Y cells. Treating cells with this physical stimulation beforehand significantly improved the cell viability and decreased the ROS content. The underlying mechanisms may be due to the activation of Akt pathway and the downstream antioxidant and prosurvival proteins. The findings manifest significant potential of TC-HT in neuroprotection, via inhibition of oxidative stress and cell apoptosis. It is believed that coupled with the use of drugs or natural compounds, this methodology can be even more effective in treating NDDs.

ObjectiveTo assess the associations of the Assessment of Spondyloarthritis International Society Health Index (ASAS HI) with gender and other factors in patients with ankylosing spondylitis (AS).MethodsFrom November 2017 to October 2018, we measured the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the ASAS HI score for AS patients at the Taichung Veterans General Hospital. After adjusting for disease activity (ASDAS-erythrocyte sedimentation rate [ESR], ASDAS- C-reactive protein [CRP], BASDAI+ESR or BASDAI+CRP), mSASSS and other potential confounders including medications, comorbidities, and laboratory data, any associations between gender and the sum score of ASDAS HI were assessed using multiple linear regression analysis, as well as any associations between gender and an ASAS HI score >5 using multivariable logistic regression analysis.ResultsA total of 307 AS patients (62 [20.2%] females, mean age 46.4 years [S.D. 13.3], mean symptom duration 20.6 years [S.D. 12.1]) were included. Multiple linear regression analysis showed that the male gender was significantly associated with a lower ASAS HI (B = -1. 91, 95% confidence interval [CI], -2.82--1.00, p 5 than females (odds ratio = 0.15, 95% CI, 0.07-0.36, p ConclusionThis single-center, cross-sectional study revealed that a higher ASAS HI score was significantly associated with female gender and higher disease activity measures.

While systemic corticosteroids quicken patient recovery during acute exacerbations of COPD, they also have many adverse effects. The optimal duration of corticosteroid administration remains uncertain. We performed a systematic review and meta-analysis to compare patient outcomes between short- (≤7 days) and long- (>7 days) corticosteroid regimens in adults with acute exacerbations of COPD. MEDLINE, EMBASE, CENTRAL, and hand searches were used to identify eligible studies. Risk of bias was assessed using the Cochrane RoB 2.0 tool and ROBINS-I. Data were summarized as ORs (odds ratios) or MDs (mean differences) whenever possible and qualitatively described otherwise. A total of 11532 participants from eight RCTs and three retrospective cohort studies were included, with 1296 from seven RCTs and two cohort studies eligible for meta-analyses. Heterogeneity was present in the methodology and settings of the studies. The OR (using short duration as the treatment arm) for mortality was 0.76 (95% CI = 0.40–1.44, n = 1055). The MD for hospital length-of-stay was -0.91 days (95% CI = -1.81–-0.02 days, n = 421). The OR for re-exacerbations was 1.31 (95% CI = 0.90–1.90, n = 552). The OR for hyperglycemia was 0.90 (95% CI = 0.60–1.33, n = 423). The OR for infection incidence was 0.96 (95% CI = 0.59–1.156, n = 389). The MD for one-second forced expiratory volume change was -18.40 mL (95% CI = -111.80–75.01 mL, n = 161). The RCTs generally had low or unclear risks of bias, while the cohort studies had serious or moderate risks of bias. Our meta-analyses were affected by imprecision due to insufficient data. Some heterogeneity was present in the results, suggesting population, setting, and treatment details are potential prognostic factors. Our evidence suggests that short-duration treatments are not worse than long-duration treatments in moderate/severe exacerbations and may lead to considerably better outcomes in milder exacerbations. This supports the current GOLD guidelines. Trial registration: Our protocol is registered in PROSPERO: CRD42023374410. [ABSTRACT FROM AUTHOR]

Hyperthermia (HT) has shown feasibility and potency as an anticancer therapy. Administration of HT in the chemotherapy has previously enhanced the cytotoxicity of drugs against pancreatic cancer. However, the drugs used when conducting these studies are substantially conventional chemotherapeutic agents that may cause unwanted side effects. Additionally, the thermal dosage in the treatment of cancer cells could also probably harm the healthy cells. The purpose of this work was to investigate the potential of the two natural polyphenolic compounds, epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), as heat synergizers in the thermal treatment of the PANC-1 cells. Furthermore, we have introduced a unique strategy entitled the thermal cycling-hyperthermia (TC-HT) that is capable of providing a maximum synergy and minimal side effect with the anticancer compounds. Our results demonstrate that the combination of the TC-HT and the CGA or EGCG markedly exerts the anticancer effect against the PANC-1 cells, while none of the single treatment induced such changes. The synergistic activity was attributed to the cell cycle arrest at the G2/M phase and the induction of the ROS-dependent mitochondria-mediated apoptosis. These findings not only represent the first in vitro thermal synergistic study of natural compounds in the treatment of pancreatic cancer, but also highlight the potential of the TC-HT as an alternative strategy in thermal treatment.

Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.

BackgroundCritically-ill surgical patients are at higher risk for sarcopenia, which is associated with worse survival. Sarcopenia may impair the respiratory musculature, which can subsequently influence the outcome of ventilator weaning. Although there are a variety of weaning parameters predictive of weaning outcomes, none have tried to incorporate "muscle strength" or "sarcopenia". The aim of the current study was to explore the association between sarcopenia and difficult-to-wean (DtW) in critically-ill surgical patients. The influence of sarcopenia on ICU mortality was also analyzed.MethodsNinety-six patients undergoing mechanical ventilation in the surgical intensive care unit (ICU) were enrolled. Demographic data and weaning parameters were recorded from the prospectively collected database, and the total psoas muscle area (TPA) was determined at the level of the 3rd lumbar vertebra by computed tomography. Sarcopenia was defined by previously established cut-off points and its influence on clinical outcomes was examined. Receiver operating characteristic (ROC) curve analysis was conducted to investigate the predictive capability of TPA and weaning parameters for predicting weaning outcomes.ResultsThe median age of the studied patients was 73 years. Thirty patients (31.3%) were sarcopenic and 30 (31.3%) were defined as DtW. Eighteen patients (18.8%) had ICU mortality. Multivariate logistic regression analyses revealed that sarcopenia was an independent risk factor for DtW and ICU mortality. The area under the ROC curve (AUC) of TPA for predicting successful weaning was 0.727 and 0.720 in female and male patients, respectively. After combining TPA and conventional weaning parameters, the AUC for DtW increased from 0.836 to 0.911 and from 0.835 to 0.922 in female and male patients, respectively.ConclusionSarcopenia is an independent risk factor for DtW and ICU mortality. TPA has predictive value when assessing weaning outcomes and can be used as an effective adjunct predictor along with conventional weaning parameters.

BackgroundCardiovascular events are the leading cause of perioperative complications among patients undergoing noncardiac surgery. However, the role of echocardiography for preoperative cardiac risk stratification prior to major noncardiac surgery is still controversial.MethodsThis retrospective study included a total of 1453 patients (51% male; age, 67 ± 16) who underwent intermediate- or high-risk major abdominal surgery or orthopedic surgery at two medical centers in South Taiwan between February 2013 and June 2016. All patients underwent preoperative transthoracic echocardiography (TTE). All of the included patients were followed up for 56 days after surgery. The primary endpoints were major adverse events (MAEs), i.e., all-cause mortality and major adverse cardiovascular-cerebral events (MACCEs).ResultsA total of 35 patients (2.4%) reached the primary endpoint: 24 patients (1.6%) died, and 17 patients (1.2%) had MACCEs. Patients with postsurgery MAEs had higher average E/e' values, a lower Left ventricular (LV) ejection fraction, and higher prevalence of significant mitral regurgitation (MR) and moderate-advanced chronic kidney disease (CKD). Multivariate analysis showed that the modified Lee index and significant MR were independent prognostic predictors of MAEs.ConclusionPreoperative identification of significant MR on TTE is associated with increased MAEs at 56 days compared with that predicted by the modified Lee index alone in patients undergoing intermediate- or high-risk noncardiac surgery.

BackgroundBreast cancer is one of the most common malignancies among women. However, there remains no consensus in current literature on the incidence of autoimmune diseases among breast cancer patients. The purpose of this study was to evaluate the risks of major autoimmune diseases (MAD) including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and dermatomyositis (DMtis)/polymyositis (PM) in female breast cancer patients.MethodsUsing the Taiwanese National Health Insurance Research Database (NHIRD) records from 2003 to 2013, we identified newly-diagnosed female breast cancer patients and randomly selected females without breast cancer in the period 2007 to 2013 into a control group. We matched the two cohorts using a 1:4 ratio based on age, and the year of index date for comparison of the risk of major autoimmune diseases. We estimated and compared the relative risks of autoimmune diseases in female breast cancer patients and females without breast cancer.ResultsA total of 54,311 females with breast cancer and 217,244 matched females without breast cancer were included in this study. For SLE, the incidence rates were 2.3 (breast cancer group) vs. 10.0 (control group) per 100,000 women years; for RA rates were 19.3 (breast cancer group) vs. 42.7 (control group) per 100,000 women years; and for SS rates were 20.5 (breast cancer group) vs. 38.2 (control group) per 100,000 women years. After adjusting for potential confounders, the hazard ratios (95% confidence intervals) for female breast cancer patients vs. control group were 0.04 (0.01-0.24) for SLE; 0.03 (0.02-0.04) for RA; and 0.21 (0.09-0.48) for SS.ConclusionFemale breast cancer patients had lower risks of SLE, RA and SS when compared to female individuals without breast cancer. However, there was no significant difference in the risk of developing DMtis/PM between both groups.

BACKGROUND AND AIM:Hepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD. METHODS:A real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation. RESULTS:The sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0-1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3-81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis. CONCLUSIONS:PrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors.

Static magnetic field (SMF) has shown some possibilities for cancer therapies. In particular, the combinational effect between SMF and anti-cancer drugs has drawn scientists' attentions in recent years. However, the underlying mechanism for the drug-specific synergistic effect is far from being understood. Besides, the drugs used are all conventional chemotherapy drugs, which may cause unpleasant side effects. In this study, our results demonstrate for the first time that SMF could enhance the anti-cancer effect of natural compound, capsaicin, on HepG2 cancer cells through the mitochondria-dependent apoptosis pathway. We found that the synergistic effect could be due to that SMF increased the binding efficiency of capsaicin for the TRPV1 channel. These findings may provide a support to develop an application of SMF for cancer therapy. The present study offers the first trial in combining SMF with natural compound on anti-cancer treatment, which provides additional insight into the interaction between SMF and anti-cancer drugs and opens the door for the development of new strategies in fighting cancer with minimum cytotoxicity and side effects.

PURPOSE:This study evaluated the outcomes of hepatocellular carcinoma (HCC) patients with small normal liver volume (NLV) treated with proton beam therapy (PBT) and introduced estimated standard liver volume (eSLV) as a new constraint. MATERIALS AND METHODS:HCC patients with NLV < 800 cm3 and no distant metastasis who received treatment in our proton center were included. The doses of PBT were mainly 72.6 Gray equivalents (GyE) in 22 fractions and 66 GyE in 10 fractions according to tumor locations. The Urata equation was used to calculate eSLV. RESULTS:Twenty-two patients were treated between November 2015 and December 2016. The 1-year progression-free and overall survival rates were 40.4% and 81.8%, respectively. The 1-year in-field failure-free rate was 95.5%. NLV ranged from 483.9 to 795.8 cm3 (median = 673.8 cm3), eSLV ranged from 889.3 to 1290.0 cm3 (median = 1104.5 cm3), and the resulting NLV/eSLV ratio ranged from 44.3 to 81.2% (median = 57.7%). Non-irradiated liver volume (NILV) ranged from 232.9 to 531.6 cm3 (median = 391.2 cm3). The NILV/eSLV ratio ranged from 21.2 to 48.0% (median = 33.3%). NLV in the patients who received 20% and an rV30/eSLV ratio of >30% are acceptable.

Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common hereditary ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure. However, the pathophysiology of heart disease in FA is non-vascular and there are conflicting data on HDL-cholesterol in FA. Two studies have shown a decrease in HDL-cholesterol compared with controls and two have shown there was no difference between FA and controls. One also showed that there was no difference in serum Apo-A-I levels in FA when compared with controls. Using a highly specific stable isotope dilution mass spectrometry-based assay, we demonstrated a 21.6% decrease in serum ApoA-I in FA patients (134.8 mg/dL, n = 95) compared with non-affected controls (172.1 mg/dL, n = 95). This is similar to the difference in serum ApoA-I levels between non-smokers and tobacco smokers. Knockdown of frataxin by > 70% in human hepatoma HepG2 cells caused a 20% reduction in secreted ApoA-I. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor caused a 200% increase in HMG-CoA in the control HepG2 cells with a similar increase in the frataxin knockdown HepG2 cells, back to levels found in the control cells. There was a concomitant 20% increase in secreted ApoA-I to levels found in the control cells that were treated with simvastatin. This study provides compelling evidence that ApoA-I levels are reduced in FA patients compared with controls and suggest that statin treatment would normalize the ApoA-I levels.

Cancer is one of the most troublesome diseases and a leading cause of death worldwide. Recently, novel treatments have been continuously developed to improve the disadvantages of conventional therapies, such as prodigious expenses, unwanted side effects, and tumor recurrence. Here, we provide the first non-invasive treatment that has combined epigallocatechin gallate (EGCG), the most abundant catechin in green tea, with a low strength pulsed electric field (PEF) and a low energy ultrasound (US). It has been observed that the cell viability of human pancreatic cancer PANC-1 was decreased approximately to 20% of the control after this combination treatment for 72 h. Besides, the combined triple treatment significantly reduced the high tolerance of HepG2 cells to the EGCG-induced cytotoxicity and similarly exhibited compelling proliferation-inhibitory effects. We also found the combined triple treatment increased the intracellular reactive oxygen species (ROS) and acidic vesicles, and the EGCG-induced inhibition of Akt phosphorylation was dramatically intensified. In this study, the apoptosis inhibitor Z-VAD-FMK and the autophagy inhibitor 3-MA were, respectively, shown to attenuate the anticancer effects of the triple treatment. This indicates that the triple treatment-induced autophagy was switched from cytoprotective to cytotoxic, and hence, cooperatively caused cell death with the apoptosis. Since the EGCG is easily accessible from the green tea and mild for a long-term treatment, and the non-invasive physical stimulations could be modified to focus on a specific location, this combined triple treatment may serve as a promising strategy for anticancer therapy.

OBJECTIVES:Although betel quid (BQ) is an established risk factor of head and neck cancer (HNC), insufficiencies exist in the literature regarding the dose-response, BQ types, HNC sites, and BQ cessation. The current study was conducted to fill these insufficiencies. MATERIALS AND METHODS:A hospital-based case-control study was conducted to evaluate the association between BQ and HNC. In-person interview was conducted to collect data on BQ chewing. The current analysis included 487 men newly diagnosed with HNC and 617 male controls who were frequency-matched to the cases by age. The association between BQ and HNC was assessed using multivariable unconditional logistic regression. RESULTS:Ever BQ chewing was associated with an increased HNC risk regardless of the BQ types. A non-linear positive association between BQ and HNC was observed, with a steep rise in HNC risk for the first 5 pack-years or 200,000 minutes of BQ consumption. Every year of BQ cessation was associated with a 2.9% reduction in HNC risk; however, the risk did not reduce to the level of non-BQ chewers even after 20 years of BQ cessation. Eliminating BQ chewing may prevent 51.6% of HNCs, 62.6% of oral cancers, and 41.3% of pharyngeal cancers in Taiwan. CONCLUSION:Our results supported the positive association between BQ and HNC. BQ cessation is effective in reducing HNC risk and should be encouraged. Because BQ cessation may not reduce the HNC risk to the level of non-BQ chewers, it is important to prevent the initiation of BQ chewing.

The Chinese version of the Continuity Assessment Record and Evaluation (CARE-C) item set was developed to facilitate the assessment of post-acute care (PAC) patients in Taiwan. Considering that the length of hospital stay (LOS) has a significant effect on the total healthcare cost, determining whether the CARE-C scores could predict the LOS of PAC patients is of great interest to the PAC providers.This prospective trial included PAC patients with stroke or central nervous system injuries. The demographic data and CARE-C scores were collected after admission and before discharge. A multivariable stepwise linear regression model was used to identify the predictors of the LOS using age, sex, tube placement status, CARE-C component scores at admission, and score differences between admission and discharge as independent variables.This study included 178 patients (66 women and 112 men), with a mean age of 61.9 ± 15.6 years. Indwelling urinary catheter placement status at admission (β = 0.241, p = 0.002) was a positive predictor of the LOS, whereas age (β = -0.189, p = 0.010), core transfer subscale score at admission (β = -0.176, p = 0.020), and difference in continence subscale score (β = -0.203, p = 0.008) were negative predictors of the LOS. The model explained 14% of the total variance.Indwelling urinary catheter placement status at admission, age, core transfer subscale score at admission, and difference in the CARE-C continence subscale score were identified as predictors of the LOS. The explanatory power of these predictors might be limited due to the regulations of Taiwan's National Health Insurance.

Rheumatoid arthritis (RA) is associated with a high risk of osteoporosis and fracture. Interleukin (IL)-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA) titers are inversely associated with bone mineral density (BMD). However, the differential effect of ACPA on bone turnover marker (BTM) and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ) treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP), and C-terminal cross-linking telopeptide of type I collagen (CTX) levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years) receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038). Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008). Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.

The presence of an intracranial aneurysm is contraindicated to recombinant tissue plasminogen activator (r-tPA) treatment for acute ischemic stroke. However, it is difficult to exclude asymptomatic intracranial aneurysms by using conventional, noncontrast head computed tomography (CT), which is the only neuroimaging suggested before r-tPA. Recent case reports and series have shown that administering r-tPA to patients with a pre-existing aneurysm does not increase the bleeding risk. However, Asians are known to have a relatively higher bleeding risk, and little evidence is available regarding the risk of using r-tPA on Asian patients with intracranial aneurysms.Medical records from the Shuang Ho hospital stroke registration between July 2010 and December 2014 were retrospectively reviewed, and 144 patients received r-tPA. Unruptured intracranial aneurysms were detected using CT, or magnetic resonance or conventional angiography after r-tPA. The primary and secondary outcomes were the difference in overall intracranial hemorrhage (ICH) and symptomatic ICH after r-tPA. The differences were analyzed using Fisher's exact or Mann-Whitney U tests, and p < 0.05 was defined as the statistical significance.A total of 144 patients were reviewed, and incidental unruptured intracranial aneurysms were found in 11 of them (7.6%). No significant difference was observed in baseline demographic data between the aneurysm and nonaneurysm groups. Among patients with an unruptured aneurysm, two had giant aneurysms (7.7 and 7.4 mm, respectively). The bleeding risk was not significant different between aneurysm group (2 out of 11, 18%) with nonaneurysm group (7 out of 133, 5.3%) (p = 0.14). None of the patients with an unruptured aneurysm had symptomatic ICH, whereas one patient without an aneurysm exhibited symptomatic ICH.The presence of an unruptured intracranial aneurysm did not significantly increase the risk of overall and symptomatic ICH in Taiwanese patients after they received r-tPA.

Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy.

BACKGROUND:Right ventricular (RV) function has been found to be a major factor of exercise capacity in patients with heart failure. However, the role of RV function in exercise capacity in healthy subjects has not been well studied. This study aims to validate the role of RV strain derived from speckle tracking echocardiography for exercise capacity for health check-up subjects. METHODS:This study prospectively recruited subjects from a routine health examination. All of them were symptom free. RV function represented by RV strain was derived from speckle tracking echocardiography in addition to traditional echocardiography parameters. Functional capacity was determined by a symptom limited treadmill exercise test with the Bruce protocol. RESULTS:Among 164 recruited subjects (age 52.2 ±9.2 years, 66.4% male), 32 subjects represented impaired functional capacity (MET

Gastric carcinoma is highly prevalent throughout the world. Understanding the pathogenesis of this disease will benefit diagnosis and resolution. Studies show that miRNAs are involved in the tumorigenesis of gastric carcinoma. An initial screening followed by subsequent validation identified that miR-376c is up-regulated in gastric carcinoma tissue and the plasma of patients with the disease. In addition, the urinary level of miR-376c is also significantly increased in gastric carcinoma patients. The plasma miR-376c level was validated as a biomarker for gastric carcinoma, including early stage tumors. The induction of miR-376c was found to enrich the proliferation, migration and anchorage-independent growth of carcinoma cells and, furthermore, the repression of the expression of endogenous miR-376c was able to reduce such oncogenic phenotypes. ARID4A gene is a direct target of miR-376c. Knockdown of endogenous ARID4A increased the oncogenicity of carcinoma cells, while ARID4A was found to be drastically down-regulated in tumor tissue. Thus, expression levels of miR-376c and ARID4A mRNA tended to be opposing in tumor tissue. Our results demonstrate that miR-376c functions by suppressing ARID4A expression, which in turn enhances the oncogenicity of gastric carcinoma cells. It seems likely that the level of miR-376c in plasma and urine could act as invaluable markers for the detection of gastric carcinoma.

The objective of this study is to determine the risk of tuberculosis (TB) disease in biologics users among rheumatoid arthritis (RA) patients in Taiwan from 2000 to 2015. This retrospective cohort study enrolled adult RA patients initiated on first biologics at Taichung Veterans General Hospital. TB risks were determined as hazard ratio (HR) with 95% confidence interval (CI) using cox regression. A total of 951 patients were recruited; etanercept (n = 443), adalimumab (n = 332), abatacept (n = 74), golimumab (n = 60), tocilizumab (n = 31) and tofacitinib (n = 11). Twenty-four TB cases were identified; 13 in etanercept and 11 in adalimumab group with the TB incidence rate of 889.3/ 100,000 and 1055.6/ 100,000 patient-years respectively. There was no significant difference in TB risk between adalimumab and etanercept users with an incidence rate ratio of 1.27 (p = 0.556 by Poisson model). Significant 2-year TB risk factors included elderly patient >65 year-old (HR: 2.72, 95% CI: 1.06-6.99, p = 0.037), history of TB (HR: 6.24, 95% CI: 1.77-22.00, p = 0.004) and daily glucocorticoid use ≥5mg (HR:5.01, 95% CI: 1.46-17.21, p = 0.010). Sulfasalazine treatment appeared to be protective (HR: 0.32, 95% CI: 0.11-0.97, p = 0.043). Risk management plan (RMP) for TB before initiation of biologics commenced in 2012. The 2-year TB risks after RMP was compared with that before 2012 (HR:0.67, 95% CI: 0.30-1.49, p = 0.323). Elderly RA patients with a history of previous TB infection and concomitant moderate dose glucocorticoid were at higher risk of TB disease. Concurrent sulfasalazine treatment appeared to be a protective factor against TB disease.

Gene flow between species may last a long time in plants. Reticulation inevitably causes difficulties in phylogenetic reconstruction. In this study, we looked into the genetic divergence and phylogeny of 20 Lilium species based on multilocus analyses of 8 genes of chloroplast DNA (cpDNA), the internally transcribed nuclear ribosomal DNA (nrITS) spacer and 20 loci extracted from the expressed sequence tag (EST) libraries of L. longiflorum Thunb. and L. formosanum Wallace. The phylogeny based on the combined data of the maternally inherited cpDNA and nrITS was largely consistent with the taxonomy of Lilium sections. This phylogeny was deemed the hypothetical species tree and uncovered three groups, i.e., Cluster A consisting of 4 taxa from the sections Pseudolirium and Liriotypus, Cluster B consisting of the 4 taxa from the sections Leucolirion, Archelirion and Daurolirion, and Cluster C comprising 10 taxa mostly from the sections Martagon and Sinomartagon. In contrast, systematic inconsistency occurred across the EST loci, with up to 19 genes (95%) displaying tree topologies deviating from the hypothetical species tree. The phylogenetic incongruence was likely attributable to the frequent genetic exchanges between species/sections, as indicated by the high levels of genetic recombination and the IMa analyses with the EST loci. Nevertheless, multilocus analysis could provide complementary information among the loci on the species split and the extent of gene flow between the species. In conclusion, this study not only detected frequent gene flow among Lilium sections that resulted in phylogenetic incongruence but also reconstructed a hypothetical species tree that gave insights into the nature of the complex relationships among Lilium species.

BACKGROUND: The current study evaluated the association between tea consumption and head and neck cancer (HNC) in Taiwan, where tea is a major agricultural product and a popular beverage. METHODS: Interviews regarding tea consumption (frequency, duration, and types) were conducted with 396 HNC cases and 413 controls. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with tea drinking, adjusted for sex, age, education, cigarette smoking, betel quid chewing, and alcohol drinking. RESULTS: A reduced HNC risk associated with tea drinking (OR for every cup per day = 0.96, 95% CI: 0.93-0.99; OR for ≧5 cups per day = 0.60, 95% CI: 0.39-0.94) was observed. The association was especially significant for pharyngeal cancer (OR for every cup per day = 0.93, 95% CI: 0.88-0.98; OR for ≧5 cups per day = 0.32, 95% CI: 0.16-0.66). A significant inverse association between HNC and tea consumption was observed particularly for green tea. CONCLUSIONS: This study suggests that tea drinking may reduce the risk of HNC. The anticancer property of tea, if proven, may offer a natural chemopreventive measure to reduce the occurrence of HNC.

BACKGROUND:There are racial and ethnic differences in the prevalence of gestational diabetes mellitus (GDM). Prior meta-analyses included small samples and very limited non-Caucasian populations. Studies to determine the relationship between transcription factor 7 like-2 (TCF7L2) rs7903146 polymorphism and risk of GDM in Hispanics/Latinos are recently available. The present meta-analysis was to estimate the impact of allele variants of TCF7L2 rs7903146 polymorphism on GDM susceptibility in overall population and racial/ethnic subgroups. METHODS:Literature was searched in multiple databases including PubMed, Web of Science, EMBASE (Ovid SP), Airiti Library, Medline Complete, and ProQuest up to July 2015. Allelic frequency for TCF7L2 rs7903146 polymorphism in GDM and control subjects was extracted and statistical analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0 statistical software. The association between TCF7L2 rs7903146 polymorphism and GDM risk was assessed by pooled odd ratios (ORs) using five gene models (dominant, recessive, homozygote, heterozygote, and allele). Stratified analysis based on race/ethnicity was also conducted. The between-study heterogeneity and contribution of each single study to the final result was tested by Cochran Q test and sensitivity analyses, respectively. Publication bias was evaluated using Egger's linear regression test. RESULTS:A total of 16 studies involving 4,853 cases and 10,631 controls were included in this meta-analysis. Significant association between the T-allele of rs7903146 and GDM risk was observed under all genetic models, dominant model (OR = 1.44, 95% CI = 1.19-1.74), recessive model (OR = 1.35, 95% CI = 1.08-1.70), heterozygous model (OR = 1.31, 95% CI = 1.12-1.53), homozygous model (OR = 1.67, 95% CI = 1.31-2.12), and allele model (OR = 1.31, 95% CI = 1.12-1.53). Stratified analysis by race/ethnicity showed a statistically significant association between rs7903146 polymorphism and susceptibility to GDM under homozygous genetic model (TT versus CC) among whites, Hispanics/Latinos and Asians. Sensitivity analysis showed that the overall findings were robust to potentially influential decisions of the 16 studies included. No significant evidence for publication bias was observed in this meta-analysis for overall studies and subgroup studies. CONCLUSIONS:This meta-analysis showed that the T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of GDM in overall population in white, Hispanic/Latino and Asian sub-groups. Asians with homozygous TT allele of rs7903146 polymorphism have highest risk of GDM (OR = 2.08) followed by Hispanics/Latinos (OR = 1.80) and whites (OR = 1.51). The highest and lowest frequency of T allele of rs7903146 was found in Malaysia and South Korea, respectively. Future studies are needed to profile genetic risk for GDM among high risk Asian and Pacific Islander subgroups.

Hypertensive disorder can cause cardiac deformities. Elastic characteristic parameters, like Young's modulus of elasticity (E) derived from a traditional cylindrical model, increase significantly with aging. However, the geometric and component changes of aging hearts because of chronic hypertension remain unknown. To better describe the effects, we propose an elliptical elastic and mathematical model to evaluate myocardial stiffness. Ninety-six hypertensive patients (HTNPos) (men: 59.3%; age ≥ 65 years: 20.8%) were enrolled and compared with normotensive controls (HTNNeg) (n = 47, 48.9%). HTNPos patients had a thicker interventricular septum in diastole (IVSd) (HTNPos: 0.96 ± 0.21 cm vs. HTNNeg: 0.77 ± 0.15; p = 0.005) and higher intracardiac pressure (e/e': 9.06 ± 4.85 cm vs. 7.76 ± 3.41; p = 0.01), especially the elderly (> 65 years) (IVSd: 1.03 ± 0.19 cm, e/e': 11.39 ± 1.99; p = 0.006 and 0.01, respectively). Nevertheless, the internal dimension decreased more significantly in the HTNPos rather than in the HTNNeg elderly (5.23 ± 0.46 vs. 4.74 ± 0.69 cm; p = 0.02). We found different directions of cardiac remodeling with normotensive and hypertensive loads. Different from the longitudinal and circumferential strain, E and Poisson's ratio (υ) are values that directly present the rigidity of myocardium. E was significantly higher in the elderly (8011.92 ± 2431.85 vs. 6052.43 ± 3121.50; p = 0.02), whereas υ was significantly higher in all HTNPos patients (0.73 ± 0.12 vs. 0.61 ± 0.07; p < 0.001). Because E and υ reflected the material changes of myocardium in the HTNPos elderly, the proposed elliptical mathematical heart model better describes the geometric deformity induced by aging and hypertension.

Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still's disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome.Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites.Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p

BACKGROUND: Although the relationship between allergy and cancer has been investigated extensively, the role of allergy in head and neck cancer (HNC) appears less consistent. It is not clear whether allergies can independently influence the risk of HNC in the presence of known strong environmental risk factors, including consumption of alcohol, betel quid, and cigarette. METHODS: THE CURRENT PAPER REPORTS RESULTS FROM: 1) an original hospital-based case-control study, which included 252 incident cases of HNC and 236 controls frequency-matched to cases on sex and age; and 2) a meta-analysis combining the results of the current case-control study and 13 previously published studies (9 cohort studies with 727,569 subjects and 550 HNC outcomes and 5 case-control studies with 4,017 HNC cases and 10,928 controls). RESULTS: In the original case-control study, we observed a strong inverse association between allergies and HNC [odds ratio = 0.41, 95% confidence interval (CI): 0.27-0.62]. The meta-analysis also indicated a statistically significant inverse association between HNC and allergies [meta-relative risk (RR) = 0.76, 95% CI: 0.63-0.91], particularly strong for allergic rhinitis (meta-RR = 0.55, 95% CI: 0.40-0.76). In addition, the inverse association between allergies and HNC was observed only among men (meta-RR = 0.67, 95% CI: 0.54-0.84) but not among women (meta-RR = 0.98, 95% CI: 0.81-1.18). CONCLUSIONS: These findings suggest that immunity plays an influential role in the risk of HNC. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are warranted to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help devise effective strategies to reduce and treat HNC.

Dendritic cell (DC) vaccines are a newly emerging immunotherapeutic approach for the treatment and prevention of cancer, but major challenges still remain particularly with respect to clinical efficacy. Engineering and optimization of adjuvant formulations for DC-based vaccines is one strategy through which more efficacious treatments may be obtained. In this study, we developed a new ex vivo approach for DC vaccine preparation. We evaluated two highly purified mixed polysaccharide fractions from the root of Astragalus membranaceus and Codonopsis pilosulae, named Am and Cp, for their use in enhancing the efficiency of a DC-based cancer vaccine against metastasis of 4T1 mammary carcinoma in mice. Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation. [Am+Cp]-treated DCs exhibited the strongest anti-4T1 metastasis activity in test mice. Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs. Bioinformatics analysis of the cytokine array data from treated DCs identified that [Am+Cp] is efficacious in activation of specific immune functions via mediating the expression of cytokines/chemokines involved in the recruitment and differentiation of defined immune cells. Biochemical analysis revealed that Am and Cp are composed mainly of polysaccharides containing a high level (70-95%) glucose residues, but few or no (< 1%) mannose residues. In summary, our findings suggest that the specific plant polysaccharides Am and Cp extracted from traditional Chinese medicines can be effectively used instead of bacterial LPS as a potent adjuvant in the formulation of a DC-based vaccine for cancer immunotherapies.

Interleukin (IL)-20 is a proinflammatory cytokine in the IL-10 family. IL-20 is associated with tumor promotion in the pathogenesis of oral, bladder, and breast cancer. However, little is known about the role of IL-20 in prostate cancer. We hypothesize that IL-20 promotes the growth of prostate cancer cells. Immunohistochemical staining showed that IL-20 and its receptors were expressed in human PC-3 and LNCaP prostate cancer cell lines and in prostate tumor tissue from 40 patients. In vitro, IL-20 upregulated N-cadherin, STAT3, vimentin, fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF-κB signals in PC-3 cells. We investigated the effects of anti-IL-20 monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor growth, suppressed tumor-mediated osteolysis, and protected bone mineral density after intratibial injection of prostate cancer cells. We conclude that IL-20 is involved in the cell migration, colony formation, and tumor-induced osteolysis of prostate cancer. Therefore, IL-20 might be a novel target for treating prostate cancer.

Trichomonas vaginalis is a protozoan parasite that occurs in the urogenital-vaginal tract and is the primary causative agent of trichomoniasis, a common sexually transmitted disease in humans. The aggregation of this protozoan tends to destroy epithelial cells and induce pathogenesis.This study cultured T. vaginalis and human cervical epithelial cells (Z172) under the same conditions in the experiments. Following co-culturing for ten hours, the protozoans became attached to Z172, such that the cells presented a round shape and underwent shrinkage. Time-lapse recording and flow cytometry on interacted Z172 revealed that 70% had been disrupted, 18% presented a necrosis-like morphology and 8% showed signs of apoptosis. Gene expression profiling revealed in the seven inflammatory Z172 genes as well as in T. vaginalis genes that code for adhesion proteins 65 and 65-1.These results suggest that cytopathogenic effects progress while Z172 is in contact with T. vaginalis, and the resulting morphological changes can be categorized as disruption.

The knowledge about short-term outcomes of nonagenarians undergoing surgery for hip fracture in Asian is limited.The patients with hip fractures who underwent hip hemiarthroplasty and open reduction with internal fixation (ORIF) for management during the period from 2008 to 2012 were identified and their medical record was retrospectively reviewed.During the study period, a total of 101 patients underwent surgery for management of hip fractures, and the age of patients ranged from 90 to 96 years. The sites of hip fracture were intertrochanteric (n = 57, 56.4%) and the neck of the femur (n = 44, 43.6%). Most of the patients had American Society of Anesthesiologists scores of 3(n = 55) or 4 (in 44 patients). 80.2% (n = 81) underwent the operation within one day after admission; however, there were 13 patients (12.9%) that underwent surgery 48 or more hours later. ORIF and hemiarthroplasty were performed for 63 (62.4%) and 38 (37.6%) patients, respectively. Overall, the 30-day and 1-year mortality rates were 9.9% (10/101) and 17.3% (13/75), respectively. Multivariate analysis showed that the 30-day mortality was significantly associated only with end-stage renal disease (ESRD) (Odds ratio, 11.13, 95% confidence interval, 1.275-97.881, P = .029).The short-term outcome of surgical management for Asian nonagenarians with hip fractures is favorable in selected patients.

The humanized monoclonal antibody-drug conjugate trastuzumab emtansine (T-DM1, Kadcyla) has been approved by the U.S. FDA to treat human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer. Despite its effectiveness in most patients, some are initially resistant or develop resistance. No biomarker of drug resistance to T-DM1 has been identified. Antibody-drug efficacy is associated with antibody internalization in the cell; therefore, cellular sensitivity of cells to the drug may be linked to cellular vesicle trafficking systems. Caveolin-1 is a 22 KD protein required for caveolae formation and endocytic membrane transport. In this study, the relationship between caveolin-1 expression and the chemosensitivity of HER-2-positive breast cancer cells to T-DM1 was investigated. Samples from 32 human breast cancer biopsy and normal tissue specimens were evaluated immunohistochemically for caveolin-1 expression. Caveolin-1 was shown to be expressed in 68% (22/32) of the breast cancer specimens. In addition, eight (72.7%, 8/11) HER-2 positive breast cancer specimens had a higher caveolin-1 expression than normal tissues. HER-2-positive BT-474 and SKBR-3 breast cancer cells that express low and moderate levels of caveolin-1, respectively, were treated with trastuzumab or its conjugate T-DM1. Cell viability and molecular localizations of caveolin-1, antibody and its conjugate were examined. Confocal microscopy showed that T-DM1 and caveolin-1 colocalized in SKBR-3 cells, which also were five times more sensitive to the conjugate in terms of cell survival than BT-474 cells, although T-DM1 also showed improved drug efficacy in BT-474 cells than trastuzumab treatment. Caveolin-1 expression in these lines was manipulated by transfection of GFP-tagged caveolin-1 or caveolin-1 siRNA. BT-474 cells overexpressing caveolin-1 were more sensitive to T-DM1 treatment than mock-transfected cells, whereas the siRNA-transfected SKBR-3 cells had decreased sensitivity to T-DM1 than mock-transfected SKBR-3 cells. The expression of caveolin-1 could mediate endocytosis and promote the internalization of T-DM1 into HER-2 positive cancer cells. Thus, caveolin-1 protein may be an effective predictor for determining the outcome of T-DM1 treatment in breast cancer patients.