Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

Gelatin methacrylate/carboxybetaine methacrylate hydrogels with tunable crosslinking for controlled drug release.

In this work, methacrylated gelatin (GelMA) based hydrogels were fabricated with carboxybetaine methacrylate (CBMA) to manipulate the properties of the gelatin-based hydrogels, since CBMA is a much smaller compound compared to gelatin. With the incorporation of CBMA, these hydrogels demonstrated better mechanical properties, a slower degradation rate, and a controlled drug release rate compared with the GelMA alone group. GelMA/CBMA hydrogels also showed good cell viability. As in the in vivo test, vascular endothelial growth factor (VEGF)-loaded GelMA/CBMA hydrogels displayed certain degrees of angiogenesis. These results indicate that GelMA/CBMA hydrogels are biocompatible, and the properties of GelMA/CBMA hydrogels can be easily tuned with the ratio of CBMA. These characteristics make the GelMA/CBMA hydrogel a promising material for drug delivery and tissue engineering.

CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

CCN family protein 2 (CCN2), also known as connective tissue growth factor, is a secreting protein that modulates multiple cellular events. We previously demonstrated the metastasis-suppressive effect of CCN2 in lung cancer cells. In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing cancer metastasis. CCN2 binds to the epidermal growth factor receptor (EGFR) and triggers ubiquitination by inhibiting the formation of the ß-pix/Cbl complex, resulting in the degradation of EGFR. Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular signal-regulated kinase but increases the expression of death-associated protein kinase, which leads to anoikis. Overall, our findings provide evidence validating the use of CCN2 as an anti-metastatic therapy in lung cancer patients, and prospect a potential therapeutic synergy between CCN2 and the anti-EGFR antibody for the treatment of lung cancer.

Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial.

BACKGROUND: Patients with dengue can experience a variety of serious complications including hypovolemic shock, thrombocytopenia, and bleeding. These problems occur as plasma viremia is resolving and are thought to be immunologically mediated. Early corticosteroid therapy may prevent the development of such complications but could also prolong viral clearance. METHODS: We performed a randomized, placebo-controlled, blinded trial of low-dose (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in Vietnamese patients aged 5-20 years admitted with dengue and fever for ≤72 hours, aiming to assess potential harms from steroid use during the viremic phase. Intention-to-treat analysis was performed using linear trend tests with a range of clinical and virological endpoints specified in advance. In addition to recognized complications of dengue, we focused on the are under the curve for serial plasma viremia measurements and the number of days after enrollment to negative viremia and dengue nonstructural protein 1 status. RESULTS: Between August 2009 and January 2011, 225 participants were randomized to 1 of the 3 treatment arms. Baseline characteristics were similar across the groups. All patients recovered fully and adverse events were infrequent. Aside from a trend toward hyperglycemia in the steroid recipients, we found no association between treatment allocation and any of the predefined clinical, hematological, or virological endpoints. CONCLUSIONS: Use of oral prednisolone during the early acute phase of dengue infection was not associated with prolongation of viremia or other adverse effects. Although not powered to assess efficacy, we found no reduction in the development of shock or other recognized complications of dengue virus infection in this study.

Faecal occult blood screening: knowledge, attitudes, and practice in four Hong Kong primary care clinics.

OBJECTIVES. To assess primary care patients for their awareness, knowledge, and attitude towards colorectal cancer and screening, to report on the uptake of faecal occult blood test screening and the results of screening, and explore predictors of screening uptake. DESIGN. Cross-sectional study. SETTING. Four primary care clinics in Hong Kong. PATIENTS. A total of 1664 patients aged 50 to 74 years attending the clinics in the period July 2006 to July 2007. MAIN OUTCOME MEASURES. Percentage of subjects who were aware that colorectal cancer is common and curable at an early stage, and who knew that faecal occult blood test or colonoscopy is useful for screening; relevant knowledge score; uptake rate of faecal occult blood testing; rate of testing positive; and factors predicting uptake. RESULTS. A total of 1645 questionnaires were collected. In all, 89% (95% confidence interval, 88-91%) were aware that colorectal cancer is common, 95% (94-96%) believed faecal occult blood test and colonoscopy are useful for screening, and 58% (56-61%) achieved a knowledge score of 50% or above. The uptake rate of the faecal occult blood test was 35%. Uptake was higher among those with a positive family history (odds ratio=1.57; 95% confidence interval, 1.08-2.27; P=0.02), those who were more aware that colorectal cancer is common (1.86; 1.29-2.69; P=0.001), and that colorectal cancer is potentially curable at an early stage (1.76; 1.32-2.36; P=0.0001). Rate of testing positive was 2.1% (95% confidence interval, 0.9-3.3%); no colorectal cancer was detected and the neoplasia detection rate (for cancers and adenomas) was 5.1 per 1000 subjects screened. CONCLUSIONS. Patients were aware that colorectal cancer is common in our community, and faecal occult blood test or colonoscopy is useful for screening. The uptake of screening was low, though relatively higher for those with a positive family history and greater awareness of the high frequency and potential for cure of colorectal cancer. Faecal occult blood test positivity rate was 2.1%, and neoplasia detection rate 5.1 per 1000 screened.

Biocompatibility of Fe(3)O(4) nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells.

In order to reveal the biocompatibility of Fe(3)O(4) nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 microg ml(-1)) to higher concentration (100 microg ml(-1)) using various human glia, human breast cancer and normal cell lines. Cytotoxicity tests for human glia (D54MG, G9T, SF126, U87, U251, U373), human breast cancer (MB157, SKBR3, T47D) and normal (H184B5F5/M10, WI-38, SVGp12) cell lines exhibited almost nontoxicity and reveal biocompatibility of Fe(3)O(4) nanoparticles in the concentration range of 0.1-10 microg ml(-1), while accountable cytotoxicity can be seen at 100 microg ml(-1). The results of our studies suggest that Fe(3)O(4) nanoparticles coated with bipolar surfactant tetramethylammonium 11-aminoundecanoate are biocompatible and promising for bio-applications such as drug delivery, magnetic resonance imaging and magnetic hyperthermia.

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma.

A comprehensive microarray analysis of hepatocellular carcinoma (HCC) revealed distinct synexpression patterns during intrahepatic metastasis. Recent evidence has demonstrated that synexpression group member genes are likely to be regulated by master control gene(s). Here we investigate the functions and gene regulation of the transcription factor SOX4 in intrahepatic metastatic HCC. SOX4 is important in tumor metastasis as RNAi knockdown reduces tumor cell migration, invasion, in vivo tumorigenesis and metastasis. A multifaceted approach integrating gene profiling, binding site computation and empirical verification by chromatin immunoprecipitation and gene ablation refined the consensus SOX4 binding motif and identified 32 binding loci in 31 genes with high confidence. RNAi knockdown of two SOX4 target genes, neuropilin 1 and semaphorin 3C, drastically reduced cell migration activity in HCC cell lines suggesting that SOX4 exerts some of its action via regulation of these two downstream targets. The discovery of 31 previously unidentified targets expands our knowledge of how SOX4 modulates HCC progression and implies a range of novel SOX4 functions. This integrated approach sets a paradigm whereby a subset of member genes from a synexpression group can be regulated by one master control gene and this is exemplified by SOX4 and advanced HCC.

Epidemiological study of diabetic retinopathy in a primary care setting in Hong Kong.

OBJECTIVES: To estimate the prevalence and risk factors of diabetic retinopathy in type 2 diabetic patients, and to investigate the difference in retinopathy progression in patients with normal fundi or established retinopathy at baseline and the risk factors implicated in the progression. DESIGN: Retrospective community-based study. SETTING: Ten primary care clinics in Hong Kong. PATIENTS: Type 2 diabetic patients; subsidiary analysis included subjects with more than one screening event. MAIN OUTCOME MEASURES: Patient demographics, baseline prevalence, and risk factors of diabetic retinopathy; progression of retinopathy in patients with normal fundi and established retinopathy at baseline, and the associated risk factors. RESULTS: A total of 6165 patients were recruited from January 1998 to May 2004. Primary analysis included 4423 patients with good-quality retinal photographs. The mean age of the patients was 60.36 years (standard deviation, 10.80 years; range, 28-94 years), the mean duration of diabetes was 4.71 years (standard deviation, 4.67 years; range, 0.1-40.6 years), and the mean level of glycated haemoglobin was 7.47% (standard deviation, 1.44%). The prevalence of retinopathy at baseline was 28.4%. Subsidiary analysis showed progression to sight-threatening retinopathy was more common in the group with baseline retinopathy than that without (7.9% vs 0.7%), and occurred at a faster rate (mean, 1.5 [range, 0.5-3.0] vs 2.0 [1.0-4.2] years). Logistic regression revealed that the level of glycated haemoglobin was positively associated with both the onset (P<0.001) and progression of retinopathy (P=0.03). CONCLUSION: Optimal glycaemic control is important for reducing sight-threatening retinopathy. Close observation is required for patients with established retinopathy as progression occurs more rapidly.

The prevalence of microalbuminuria among patients with type II diabetes mellitus in a primary care setting: cross-sectional study.

OBJECTIVES: To determine the prevalence of microalbuminuria among patients with type II diabetes mellitus in a primary care setting, and to study the association between various risk factors and the presence of microalbuminuria. DESIGN: Cross-sectional community-based study. SETTING: Four primary care clinics, Hong Kong. PATIENTS: All patients with type II diabetes mellitus who regularly attended the clinics between May 2002 and March 2003. MAIN OUTCOME MEASURES: Patients' demographic data, the proportion with microalbuminuria (measured using a spot urine test), and the association between this condition and risk factors for diabetic nephropathy (via correlation and multivariable logistic regression analysis). RESULTS: The mean age of the 1161 patients in the sample population was 58.0 years. The mean duration of diabetes mellitus was 5.7 years, and the mean level of glycated haemoglobin was 7.4%. A total of 13.4% of the patients had microalbuminuria. Having the condition was significantly associated with advanced age, female sex, poor glycaemic control, and coexisting hypertension in both correlation and regression analyses. No significant association with ever smoking was found. CONCLUSION: Early screening for incipient diabetic nephropathy and aggressive management of modifiable risk factors in a primary care setting may be important in optimising the renal outcome of patients with type II diabetes mellitus.

Rectal cancer mortality and total hardness levels in Taiwan's drinking water.

The possible association between the risk of rectal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (986 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and rectal cancer mortality. Odds ratio and 95% confidence intervals were 1.24 (1.01-1. 55) and 1.38 (1.10-1.73), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for rectal cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.

Effects of indoor environmental factors on risk for acute otitis media in a subtropical area.

The objective of this study was to examine the relationship between indoor environmental factors and acute otitis media in a subtropical area. A case-control study was performed using participants from a prevalence survey that included 219 school children with acute otitis media and 219 age- and gender-matched controls. The study was confined to 4164 primary school children aged 6-12 yr attending 8 primary schools in Kaohsiung rural municipalities who participated in a prevalence study of the health effects of an indoor environment. An acute otitis media case was defined as a child with acute symptoms (presenting with earache, fever, irritability, and/or discharge from the ear) diagnosed by a physician in the previous year. Controls selected from the same school did not have chronic or acute respiratory illness or an ear-related illness during the same period. Information regarding the home environment was obtained using a structured written questionnaire, completed by the parents of the children. Of the many indoor environmental factors included in this study, only living in a home with indications of dampness (mold, flooding, home dampness) showed an association with acute otitis media. It was concluded that dampness in the home is a new public health issue in subtropical areas.

Different regulation of the human thymidine kinase promoter in normal human diploid IMR-90 fibroblasts and HeLa cells.

Transcriptional activation of the human thymidine kinase (hTK) promoter plays an important role in the cell cycle control of thymidine kinase expression. Using the luciferase reporter cotransfection assay, we found that the activity of the hTK promoter in IMR-90 normal human diploid fibroblasts was increased by the constitutively over-expressed cyclin A or cyclin E but not by cyclin D, suggesting that the former two cyclins may act as positive regulators for the hTK promoter. The sequence responsible for the transcriptional activation by cyclin E was identified to be located between -133 and -92 of the hTK promoter. Regulation of the hTK promoter in HeLa cells appeared to be different from that in IMR-90 fibroblasts. Firstly, the hTK promoter in HeLa was already highly activated and could not be further activated by ectopically expressed cyclin A or E. Secondly, the -133 to -92 region of the hTK promoter was important for the promoter strength in HeLa cells but not in IMR-90 cells. The steady-state levels of cyclins A and E were readily detected in HeLa cells but not in normal IMR-90 fibroblasts. Based on these results, we propose that the cellular environment of the HeLa cell allows the hTK promoter to stay fully activated for transcription regardless of ectopically expressed cyclin A or E and that transcriptional activation of thymidine kinase gene is deregulated in these tumor cells.