An Investigation of the Differential Expression of Her2/neu Gene Expression in Normal Oral Mucosa, Epithelial Dysplasia, and Oral Squamous Cell Carcinoma in Taiwan

BackgroundHer2/neu was thought to be a proto-oncogene with sequence homology to epidermal growth factor receptor (EGFR). Its overexpression was seen in many cancers and referred to regimens of anticancer therapy. The aim of this study was to investigate whether the abnormal expression existed in oral carcinogenesis.MethodsImmunohistochemistry (IHC) was used to detect Her2/neu expression in normal oral mucosa (NOM) (n = 20), oral precancerous lesions of epithelial dysplasia (ED) (n = 20), and oral squamous cell carcinoma (OSCC) (n = 30). The association of clinicopathologic covariates of areca use, tumor size, neck lymph node metastasis, differentiation and stages of cancer with the expression of Her2/neu was examined. The significance of Neu immunoreactivity in different groups or with different covariates was investigated using Fisher's exact test.ResultsHer2/neu immunoreactivity was very low with Her2/neu(+) in 10% (2/20) of NOM cases and in 25% (5/20) of ED cases, respectively. The Her2/neu expression was high in OSCC cases, with 40% (12/30) of Her2/neu(+) and 10% (3/30) of Her2/neu(++). Significant difference was observed between NOM/ED and OSCC cases (p < 0.05). All clinicopathologic covariates showed no significant relation to the expression of Her2/neu in OSCC cases.ConclusionThese findings suggested a dynamic change in Her2/neu expression during the development of OSCC. The overexpression of Her2/neu can be used as a marker in distinguishing NOM/ED from OSCC

Induction of Apoptosis and Cell Cycle Blockade by Helichrysetin in A549 Human Lung Adenocarcinoma Cells

Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent

Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support

Introduction: Extracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission. Methods: Fifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6–20, Area 6–40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated. Results: Patients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment. Conclusions: MSsE provides additional prognostic information in patients receiving ECLS. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0548-3) contains supplementary material, which is available to authorized users

COVID-19 Antibody Surveillance Among Healthcare Workers in A Non-COVID designated Cardiology Centre

BACKGROUND: Reports on healthcare worker antibody response to COVID-19 infection are scarce. We aim to determine theCOVID-19 antibody prevalence among healthcare workers in a cardiology centre and the relationship between case definitioncriteria with the COVID-19 antibody result. METHODS: Convenience sampling was applied. Healthcare workers in SarawakHeart Centre (SHC) cardiology, radiology, and emergency unit were recruited. A survey form on clinical symptoms and closecontact history was distributed. HEALGEN COVID-19 IgG/IgM rapid test was performed using serum/ whole blood specimen.Staff with positive COVID-19 antibody results were referred to the infectious disease specialist for assessment. RESULTS: Atotal of 310 staff were screened. 220(71%) were female, and the mean age was 36±7.7 years old. 46(14.8%) staff reported havingclinical symptoms at some stage from the end of January 2020 to the time of this surveillance. Number of staff who had a historyof overseas travel, close contact with confirmed COVID-19 patients, or had visited places with identified COVID-19 clusterswere 4(1.3%), 24(7.7%) and 24(7.7%) respectively. There were 14 staff (4.5%) with positive tests positive, 2 for IgM, and 12for IgG. All those with positive antibody were subsequently tested negative with RT-PCR test. The history of having clinicalsymptoms and exposure to COVID-19 cluster area were independently associated with a positive IgG result. CONCLUSION:The application of COVID-19 antibody serology rapid tests could determine true exposure of staff to the infection and allowus to reassess existing measures of infection control within the hospital

Clinical Outcomes and Predictors of Improved Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction due to Non-Ischemic Cardiomyopathy

Background: Left ventricular ejection fraction (LVEF) improvement is the cornerstone of LV reverse remodelling. It prognosticates heart failure with reduced ejection fraction (HFrEF). There is limited data on the clinical factors that predict LVEF improvement among non-ischemic cardiomyopathy (NICM) patients in Malaysia. Objective: To determine the 3-year outcomes and predictors of LVEF improvement in patients with (NICM) and HFrEF. Materials &amp; Methods: We recruited patients with NICM and HFrEF (LVEF &lt;40%) between 2016 and 2018. NICM was defined as HF with 1) normal coronary arteries or 2) any coronary artery stenosis not involving the proximal left anterior descending artery (LAD) and without transmural fibrosis in the LAD territory from cardiac magnetic resonance (CMR) imaging to account for the impaired LVEF. Clinical and imaging parameters were assessed using logistic regression statistics to determine the predictors of LVEF improvement. LVEF improvement is defined as a recovery of EF to &gt; 40% with at least a 10-point increment from baseline. The clinical outcomes at three year were 1) change in NYHA class and 2) composite of all-cause mortality, unscheduled clinic or emergency department visits, readmission and/or ventricular arrhythmia. Results: 43 patients were recruited. The mean duration of follow-up and echocardiographic assessment interval were 46 and 23 months, respectively. The cohort had a mean age of 46±13 years, and were mostly male (72%). More patients had NYHA 1 at the end of the study (37% vs 86%). 11 patients (25%) recorded composite outcomes. 62.8% had LVEF improvement. Patients with LVEF improvement had a lower incidence of late gadolinium enhancement (51.7% vs 85.7%, odds 5.6 ,p=0.045) and midwall fibrosis on CMR (18.5% vs 62.5%, odds 7.3, p=0.003). LVEF improvement did not affect the functional NYHA recovery (92% vs 81%, p=0.28). Patients with less LVEF improvement had higher incidence of composite outcome (18.5% vs 37.5%, p=0.168). Other characteristics were not significantly different between the groups. Conclusion: Patients with NICM and LVEF improvement had lower composite outcome. Absence of late gadolinium enhancement, particularly midwall fibrosis was an independant predictor of LVEF improvement. This underscores the importance of CMR tissue characterisation to refine the prognostication of NICM patients

Prognostic Value of Leucocyte Telomere Length in Acute Myocardial Infarction

Introduction: Leucocyte telomere length (LTL) has been described as a marker of biological age, endothelial dysfunction and atherosclerosis. The association between LTL and clinical characteristics of Asian patients, and their outcomes following acute myocardial infarction (AMI) have been inconclusive. Objective: To investigate the relationship between LTL and developing AMI, the association of LTL with inpatient and 30-day mortality, and the comparison to LTL with established AMI risk scores in predicting these outcomes. Methodology: 100 patients aged 30-70 years admitted with an AMI to a tertiary referral center between May-Oct 2017 were enrolled; these were matched with 100 non-AMI ('healthy') controls for gender and age (+/- 1 year). Clinical data was obtained prospectively; inpatient and 30-day outcomes documented. LTL was reflected by a well described variable called a tis ratio (TSR). The TSR was measured at enrolment using a quantitative PCR-based methods (qPCR) and results blinded to the clinician

Characterizing and Prognosticating Heart Failure with Improved Ejection Fraction Using NT-proBNP, Growth Differentiation Factor 15 and Global Longitudinal Strain

Background: Heart failure with improved ejection fraction (HFiEF) is a novel heart failure (HF) subgroup. There are sparse data on using NT-proBNP, growth differentiation factor 15 (GDF15) and global longitudinal strain (GLS) to characterize and prognosticate HFiEF patients. Objectives: (1) To determine the level and correlation between NT-proBNP, GDF-15 and GLS in HFiEF patients. (2) To examine the correlation of each marker with NYHA, MAGGIC prognostic score, HF etiologies, comorbidities status, degree of LVEF/ LV end-diastolic diameter change from baseline and diastolic dysfunction. (3) To look for association of each marker with follow-up LVEF change and 1-year composite mortality or HF events outcome. Materials & Methods: This was a cross-sectional observational study in Sarawak Heart Centre HF clinic. 53 HfiEF patients who had NT-proBNP and GDF15 tests performed were selected. This cohort had no HF events in the past 6 months during the blood tests. Clinical characteristics, echocardiography parameters, and 1-year composite clinical outcome were analyzed retrospectively. Results: The mean age of the cohort was 52 years old and 81% were male. The cohort was highly comorbid (hypertension 71%; diabetes 45.3%; AF 17.3%). Most of the patients (87%) were asymptomatic by NYHA (I) and low rate of composite outcome was observed, 5.7%. The mean NT-proBNP, GDF-15, GLS were 357 pg/ml, 1572 pg/ml, and -12.1% respectively. There were significant moderate correlation between GDF15 with NT-proBNP (r=0.414) and NT-proBNP with GLS (r=-0.351). Higher NT-proBNP and GDF15 levels were associated with poorer MAGGIC prognostic scores (r=0.549, 0.41 respectively). NT-proBNP was the only marker associated with a higher degree of LVEF improvement compare to baseline echocardiography. NT-proBNP was also related to severe diastolic echo parameters. Hypertension and diabetes were strongly associated with higher elevated GDF15 levels. The lower mean GLS level was significantly associated with the presence of composite outcome (-6.45% vs -12.47%, p=0.0). Patients with NT-proBNP levels below the median cutoff had favourable follow-up LVEF improvement (+9.73%, p=0.035). Conclusion: In our HFiEF study cohort, NT-proBNP best correlate and prognosticate future LV remodelling. GDF15 was closely related to systemic illnesses such as diabetes. The role of GLS in our HFiEF cohort remains uncertain

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Baseline characteristics of participants in the Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program

OBJECTIVE: The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program is a diabetes prevention trial comparing the diabetes conversion rate at 3 years between the intervention group, which receives the incentivized lifestyle intervention program with stepwise addition of metformin, and the control group, which receives the standard of care. We describe the baseline characteristics and compare Pre-DICTED participants with other diabetes prevention trials cohort. RESEARCH DESIGN AND METHODS: Participants were aged between 21 and 64 years, overweight (body mass index (BMI) ≥23.0 kg/m2), and had pre-diabetes (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)). RESULTS: A total of 751 participants (53.1% women) were randomized. At baseline, mean (SD) age was 52.5 (8.5) years and mean BMI (SD) was 29.0 (4.6) kg/m2. Twenty-three per cent had both IFG and IGT, 63.9% had isolated IGT, and 13.3% had isolated IFG. Ethnic Asian Indian participants were more likely to report a family history of diabetes and had a higher waist circumference, compared with Chinese and Malay participants. Women were less likely than men to meet the physical activity recommendations (≥150 min of moderate-intensity physical activity per week), and dietary intake varied with both sex and ethnicity. Compared with other Asian diabetes prevention studies, the Pre-DICTED cohort had a higher mean age and BMI. CONCLUSION: The Pre-DICTED cohort represents subjects at high risk of diabetes conversion. The study will evaluate the effectiveness of a community-based incentivized lifestyle intervention program in an urban Asian context.Peer reviewe

Human SCARB2-Mediated Entry and Endocytosis of EV71

Enterovirus (EV) 71 infection is known to cause hand-foot-and-mouth disease (HFMD) and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2) has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2) to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pH-dependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pH-dependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus