Epicardial calcineurin-NFAT signals through Smad2 to direct coronary smooth muscle cell and arterial wall development

AIMS: Congenital coronary artery anomalies produce serious events that include syncope, arrhythmias, myocardial infarction, or sudden death. Studying the mechanism of coronary development will contribute to the understanding of the disease and help design new diagnostic or therapeutic strategies. Here, we characterized a new calcineurin-NFAT signalling which specifically functions in the epicardium to regulate the development of smooth muscle wall of the coronary arteries. METHODS AND RESULTS: Using tissue-specific gene deletion, we found that calcineurin-NFAT signals in the embryonic epicardium to direct coronary smooth muscle cell development. The smooth muscle wall of coronary arteries fails to mature in mice with epicardial deletion of calcineurin B1 (Cnb1), and accordingly these mutant mice develop cardiac dysfunction with reduced exercise capacity. Inhibition of calcineurin at various developmental windows shows that calcineurin-NFAT signals within a narrow time window at embryonic Day 12.5-13.5 to regulate coronary smooth muscle cell development. Within the epicardium, NFAT transcriptionally activates the expression of Smad2, whose gene product is critical for transducing transforming growth factor β (TGFβ)-Alk5 signalling to control coronary development. CONCLUSION: Our findings demonstrate new spatiotemporal and molecular actions of calcineurin-NFAT that dictate coronary arterial wall development and a new mechanism by which calcineurin-NFAT integrates with TGFβ signalling during embryonic development

The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities

BACKGROUND AND AIM: To evaluate the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients with unresectable huge hepatocellular carcinoma (HCC) unsuitable of other standard treatment option. METHODS: Between 2009 and 2011, 22 patients with unresectable huge HCC (≧10 cm) were treated with SBRT. dose ranged from 26 Gy to 40 Gy in five fractions. Overall survival (OS) and disease-progression free survival (DPFS) were determined by Kaplan-Meier analysis. Tumor response and toxicities were also assessed. RESULTS: After a median follow-up of 11.5 month (range 2–46 months). The objective response rate was achieved in 86.3% (complete response (CR): 22.7% and partial response (PR): 63.6%). The 1-yr. local control rate was 55.56%. The 1-year OS was 50% and median survival was 11 months (range 2–46 months). In univariate analysis, Child-Pugh stage (p = 0.0056) and SBRT dose (p = 0.0017) were significant factors for survival. However, in multivariate analysis, SBRT dose (p = 0.0072) was the most significant factor, while Child-Pugh stage of borderline significance. (p = 0.0514). Acute toxicities were mild and well tolerated. CONCLUSION: This study showed that SBRT can be delivered safely to huge HCC and achieved a substantial tumor regression and survival. The results suggest this technique should be considered a salvage treatment. However, local and regional recurrence remain the major cause of failure. Further studies of combination of SBRT and other treatment modalities may be reasonable

The incidence of symptomatic venous thromboembolism following hip fractures with or without surgery in Taiwan

AbstractBackgroundInformation on the incidence of venous thromboembolism (VTE) following hip fractures in Asia is rare. This study will investigate the epidemiology of symptomatic VTE in Taiwanese patients experiencing hip fractures.Methods and resultsWe used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≧45years) who experienced hip fractures from 1998 to 2007 and were followed up for 3months after the discharge. Logistic regression analysis determined the independent risk factors of symptomatic VTE after the fractures. We identified 134,034 patients (mean age: 76.2±9.7years; female: 57.8%) who experienced hip fractures, 83.2% of whom underwent hip surgery. The overall pharmacological thromboprophylaxis rate was 2.7%. The mean length of stay was 11.3±7.9days. The 3-month cumulative incidence of symptomatic VTE was 77 events per 10,000 persons. Multivariate analysis showed that previous DVT, previous PE, varicose veins, cancer, heart failure, renal insufficiency, and older age were independent risk factors of developing VTE.ConclusionsThe incidence of symptomatic VTE after hip fractures is low in Taiwan. Patients rarely received pharmacological thromboprophylaxis following hip fractures. Universal thromboprophylaxis for patients experiencing hip fractures was not necessary in Taiwan, but it should be considered in high-risk populations

Co-seismic signatures in magnetometer, geophone, and infrasound data during the Meinong Earthquake

This paper utilizes 10 stations of co-located seismometer, QuakeFinder/infrasound to observe co-seismic signatures triggered by the 6 February 2016 M 6.6 Meinong Earthquake. Each QuakeFinder system consists of a 3-axes induction magnetometer, an air conductivity sensor, a geophone, and temperature/relative humidity sensors. There are no obvious charges in the positive/negative ions, the temperature, and the humidity, while the magnetometer, the geophone, and infrasound data detect clear co-seismic signatures, similar to seismic waves recorded by seismometers. The magnetometers register high-frequency pulsations, like seismic waves, and superimpose with low-frequency variations, which could be caused by the magnetometer shaking/tilting and/or the underground water level change, respectively, upon the arrival of seismic waves. The spectrum centering around 2.0 Hz of the co-seismic geophone fluctuations is similar to that of the seismic waves. However, the energy of co-seismic geophone fluctuations (also magnetometer pulsations) yields an exponential decay to the distance of a station to the epicenter, while the energy of the seismic waves is inversely proportional to the square of the distance. This suggests that the mechanisms for detecting seismic waves of the QuakeFinder system and seismometers are different. In general, the geophone and magnetometer/infrasound system are useful to record high- and low-frequency seismic waves, respectively

Biomechanical investigation of flexor digitorum tendons in trigger finger patients using sonography

Trigger finger (TF) has generally been ascribed to primary changes in the first annular (A1) pulley. Repeated friction between the A1 pulley and flexor digitorum tendons could result in swelling of soft tissues, and thus it has been speculated that TF affects tendons’ biomechanical behaviors. However, the pathology mechanism related to these behaviors remains unclear. The purposes of this study are to understand (1) the variations in the morphologies of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) between normal fingers and TFs, (2) the differences in the biomechanical behaviors of the FDP and FDS between normal fingers and TFs in various finger flexion positions, and (3) the effect of various finger positions on the biomechanical behaviors of the FDP and FDS

戲劇教育介入於國小高年級學生性知識、性態度、性健康生活技能自我效能之效果探討一以南投縣國小為例

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REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT

Background. Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patientspecific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. Methods. A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. Results. Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. Conclusion. In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decisionmaking more accurately for those patients

Adjuvant chemotherapy and survival outcomes in rectal cancer patients with good response (ypT0-2N0) after neoadjuvant chemoradiotherapy and surgery: A retrospective nationwide analysis

BackgroundFor rectal cancer, it remains unclear how to incorporate tumor response to neoadjuvant chemoradiotherapy (nCRT) when deciding whether to give adjuvant chemotherapy. In this study, we aim to determinate the survival benefit of adjuvant chemotherapy for rectal cancer patients with good response (ypT0-2N0) after nCRT and surgery.MethodsThe study cohort included 720 rectal cancer patients who had good response (ypT0-2N0) after nCRT and surgery, who did or did not receive adjuvant chemotherapy between January 2007 and December 2017, from the Taiwan Cancer Registry and National Health Insurance Research database. The Kaplan–Meier method, log-rank tests, and Cox regression analysis were performed to investigate the effect of adjuvant chemotherapy on 5-year overall survival (OS) and disease-free survival (DFS).ResultsOf 720 patients, 368 (51.1%) received adjuvant chemotherapy and 352 (48.9%) did not. Patients who received adjuvant chemotherapy were more likely to be female, younger (≤ 65), with advanced clinical T (3-4)/N (1-2) classification and ypT2 classification. No significant difference in 5-year OS (p=0.681) or DFS (p=0.942) were observed by receipt of adjuvant chemotherapy or not. Multivariable analysis revealed adjuvant chemotherapy was not associated with better OS (adjusted hazard ratio [aHR], 1.03; 95% Confidence Interval [CI], 0.88-1.21) or DFS (aHR, 1.05; 95% CI, 0.89-1.24). Stratified analysis for OS and DFS found no significant protective effect in the use of adjuvant chemotherapy, even for those with advanced clinical T or N classification.ConclusionAdjuvant chemotherapy may be omitted in rectal cancer patients with good response (ypT0-2N0) after nCRT and surgery