Activation of the renin–angiotensin–aldosterone system (RAAS) results in vasoconstriction, muscular (vascular and cardiac) hypertrophy and fibrosis. Established arterial stiffness and cardiac ...dysfunction are key factors contributing to subsequent cardiovascular and renal complications. Blockade of RAAS has been shown to be beneficial in patients with hypertension, acute myocardial infarction, chronic systolic heart failure, stroke and diabetic renal disease. An aggressive approach for more extensive RAAS blockade with combination of two commonly used RAAS blockers ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) yielded conflicting results in different patient populations. Combination therapy is also associated with more side effects, in particular hypotension, hyperkalaemia and renal impairment. Recently published ONTARGET study showed ACEI/ARB combination therapy was associated with more adverse effects without any increase in benefit. The Canadian Hypertension Education Program responded with a new warning: ‘Do not use ACEI and ARB in combination’. However, the European Society of Cardiology in their updated heart failure treatment guidelines still recommended ACEI/ARB combo as a viable option. This apparent inconsistency among guidelines generates debate as to which approach of RAAS inhibition is the best. The current paper reviews the latest evidence of isolated ACEI or ARB use and their combination in cardiovascular diseases, and makes recommendations for their prescriptions in specific patient populations.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and ...inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3′ untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-N-(3,5-difluorophenacetyl)-l-alanyl-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme.
The benefits of narrow band imaging (NBI) on enhancing colorectal adenoma detection remain questionable. We tested whether the new generation of NBI (190-NBI), which is twice as bright as the ...previous version, would improve adenoma detection when compared with high-definition white light (HD-WL) colonoscopy.
It was a randomized controlled trial with tandem colonoscopy. We recruited patients who underwent colonoscopy for symptoms, screening, or surveillance. Patients were randomized for the use of either 190-NBI or HD-WL on withdrawal. Tandem colonoscopy was performed by using the same assigned colonoscope and withdrawal method. Lesions detected on first-pass and second-pass examination were used for adenoma detection and miss rates, respectively. The primary outcomes were adenoma and polyp detection rates.
A total of 360 patients were randomized to undergo either 190-NBI or HD-WL colonoscopy. Both the adenoma and polyp detection rates were significantly higher in the 190-NBI group compared with the HD-WL group (adenoma: 48.3% vs. 34.4%, P=0.01; polyps: 61.1% vs. 48.3%, P=0.02). The mean number of polyps detected per patient was higher in the 190-NBI group (1.49% vs. 1.13, P=0.07). There was no significant difference in the adenoma miss rates between the two groups (21.8% vs. 21.2%). Multivariate analysis showed that the use of 190-NBI (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.10-3.12), withdrawal time (OR 1.29; CI 1.19-1.38), patient's age (OR 1.04; CI 1.01-1.06), and male gender (OR 2.38; CI 1.42-3.99) were associated with adenoma detection.
190-NBI colonoscopy was superior to the conventional HD-WL in detecting colorectal adenomas or polyps, but there was no significant difference in adenoma miss rates.
Social media use is widely accepted in higher education, connecting students’ learning with daily life. Considering the potential of social media to revolutionize the whole spectrum of teaching and ...learning, this study examines social media usage of business school students of different majors and their perception of social media as learning aids through a quantitative online survey guided by the 5E instructional model, with 423 valid responses from students majoring in accounting, finance, and economics. Results indicated that respondents perceived social media as influential in helping them access study-related information. It facilitated comprehensive learning, information access, information sharing, and student communication with instructors. Significant differences in perceptions of using social media as aids for business learning were found among students of different demographics, including gender, education level, and residence, but not quite for different majors. While various studies have examined the use of social media in education, scant studies focus on business school students under the lens of the 5E instructional model, especially Asians.
Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving ...rituximab-containing chemotherapy have not been well described.
HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered.
Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients.
A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.
Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–negative, antibody to hepatitis B core antigen (anti‐HBc)–positive patients after allogeneic hematopoietic stem cell ...transplantation (HSCT) has not been prospectively studied. HBsAg‐negative, anti‐HBc–positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg‐negative, anti‐HBc–positive, of whom 62 were recruited and monitored for a median of 48 (4‐104) weeks. The 2‐year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8‐100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft‐versus‐host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft‐versus‐host disease, compared with the remaining patient cohort, had a significantly lower 2‐year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. Conclusion: HBsAg‐negative, anti‐HBc–positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft‐versus‐host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451‐1461).
Principal component analysis of dry-bulb temperature, wet-bulb temperature and global solar radiation was considered, and a new climatic index (principal component
Z) determined for two emissions ...scenarios – low and medium forcing. Multi-year building energy simulations were conducted for generic air-conditioned office buildings in Harbin, Beijing, Shanghai, Kunming and Hong Kong, representing the five major architectural climates in China. Regression models were developed to correlate the simulated monthly heating and cooling loads and building energy use with the corresponding
Z. The coefficient of determination (
R
2) was largely within 0.78–0.99, indicating strong correlation. A decreasing trend of heating load and an increasing trend of cooling load due to climate change in future years were observed. For low forcing, the overall impact on the total building energy use would vary from 4.2% reduction in severe cold Harbin (heating-dominated) in the north to 4.3% increase in subtropical Hong Kong (cooling-dominated) in the south. In Beijing and Shanghai where heating and cooling are both important, the average annual building energy use in 2001–2100 would only be about 0.8% and 0.7% higher than that in 1971–2000, respectively.
Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of ...detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9-95.8%; Sensitivity: 55.5-77.8%; Specificity: 91.5-98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.
Mobile devices not only bring convenience to aspects of life but also change people’s behaviour in their daily lives, in particular reading. While most of the studies focus on reading books, there ...are few systematic publications primarily focusing on electronic periodicals, especially comparing the different needs of patrons from different faculties. Through an online questionnaire, the authors explored whether and how university patrons of the University of Hong Kong changed their reading behaviour of e-periodicals in the context of mobile devices. Six reading patterns were investigated: reading frequency, types of periodicals, preference of mobile devices, reading time spent, reading time slot and reading location. The authors purposefully compare subjects selected from three faculties (Education, Engineering and Science) to examine whether research and learning requirements affect their behaviours. The analysis found that reading patterns did indeed change after patrons adopted mobile devices to read periodicals. There are also some statistically significant differences among the faculties investigated, reflecting their different information needs. The findings can help academic libraries review their periodical subscription policies and reading promotion schemes to satisfy various patrons’ needs.
An artificial neural network (ANN) model was developed for office buildings with daylighting for subtropical climates. A total of nine variables were used as the input parameters – four variables ...were related to the external weather conditions (daily average dry-bulb temperature, daily average wet-bulb temperature, daily global solar radiation and daily average clearness index), four for the building envelope designs (solar aperture, daylight aperture, overhang and side-fins projections), and the last variable was day type (i.e. weekdays, Saturdays and Sundays). There were four nodes at the output layer with the estimated daily electricity use for cooling, heating, electric lighting and total building as the output. Building energy simulation using EnergyPlus was conducted to generate daily building energy use database for the training and testing of ANNs. The Nash–Sutcliffe efficiency coefficient for the ANN modelled cooling, heating, electric lighting and total building electricity use was 0.994, 0.940, 0.993, and 0.996, respectively, indicating excellent predictive power. Error analysis showed that lighting electricity use had the smallest errors, from 0.2% under-estimation to 3.6% over-estimation, with the coefficient of variation of the root mean square error ranging from 3% to 5.6%.
PDF
