[Association between circadian rhythm disorder and comorbidity of anxiety and depression in adolescents].

Adolescents are in a transition period from children to adults, during which they are prone to a variety of emotional disorders, with anxiety and depression being the most common disorders. Anxiety and depressive symptoms are highly correlated and the comorbidity of anxiety and depression is common. At the same time, the most prominent behavioral changes in adolescence are the emergence of getting up late and sleeping late, and the circadian rhythm begins to delay. Previous studies have shown that circadian rhythm is closely related to anxiety and depression, but the association between circadian rhythm disorder and comorbidity of anxiety and depression remains unclear. This article reviews the prevalence, association and potential biological mechanism of circadian rhythm disorder and comorbidity of anxiety and depression in adolescents, so as to provide a possible reference for the prevention and control of comorbidity of anxiety and depression in adolescents.

[Impact of interventional therapy on top of standard drug therapy on left ventricular structure and function in HFrEF patients complicating with middle aortic syndrome caused by Takayasu arteritis].

Objective: To evaluate the impact of interventional therapy on top of drug therapy on cardiac function and structure in heart failure with reduced ejection fraction (HFrEF) patients complicating with middle aortic syndrome caused by Takayasu arteritis (TA-MAS). Methods: It was a retrospective longitudinal study. The data of patients with TA-MAS and HFrEF, who received interventional therapy on top of drug therapy in Fuwai Hospital from January 2010 to September 2020, were collected and analyzed. Baseline clinical data (including demographic data, basic treatment, etc.) were collected through the electronic medical record system. Changes of indexes such as New York Heart Association (NYHA) classification, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) before and after therapy were analyzed. Results: A total of 10 patients were collected. There were 8 females in this patient cohort, age was (18.4±5.0) years and onset age was (15.3±5.0) years. All 10 patients received standard heart failure medication therapy in addition to hormone and/or immunosuppressive anti-inflammatory therapy, but cardiac function was not improved, so aortic balloon dilatation and/or aortic stenting were performed in these patients. The median follow-up was 3.3(1.3, 5.6) years. On the third day after interventional therapy, the clinical symptoms of the 10 patients were significantly improved, NYHA classfication was restored from preoperative Ⅲ/Ⅳ to Ⅱ at 6 months post intervention(P<0.05). Compared with preoperation, NT-proBNP (P=0.028), LVEDD (P=0.011) and LVMI (P=0.019) were significantly decreased, LVEF was significantly increased (P<0.001) at 6 months after operation. Compared with preoperation, NT-proBNP (P=0.016), LVEDD (P=0.023) and LVMI (P=0.043) remained decreased, LVEF remained increased (P<0.001) at 1 year after operation. Conclusion: Results from short and medium term follow-up show that interventional therapy on top of heart failure drug therpay can effectively improve left cardiac function and attenuate cardiac remodeling in patients with TA-MAS comorbid with HFrEF.

Religion and Cosmetics: Guidelines for Preparing Products Aimed at the Muslim World Based on the Interpretation of Halal Cosmetics in Malaysia.

The ingredients of cosmetic products are the mixture of chemical substances derived from natural or synthetic sources. The substances are used as either active (functional) or excipient (additional) ingredients. The source of origin of the ingredients is a critical point for the determination of halal status. Halal is an Arabic word that means things or actions that are permitted by the Islamic law. A halal product can be interpreted as something permissible for consumption by Muslims. Thus, the objective of this study was to understand the critical points for the differences between halal and general cosmetics, and their classifi cations. This study also identifies issues related to the safety of cosmetic ingredients that may affect the halal status of a cosmetic product. The method used was document and content analyses. The main documents that were analyzed include Malaysian Standard MS 2634:2019, Manual Procedure for Malaysia Halal Certification issued by the Department of Islamic Development Malaysia or Jabatan Kemajuan Islam Malaysia (JAKIM), and Guidelines for the Control of Cosmetic Products issued by the National Pharmaceutical Regulatory Agency under the Ministry of Health of Malaysia. This study finding describes four critical points of differences, namely, (i) ingredient, (ii) processing, (iii) safety, and (iv) ethics and responsibility. The classification of ingredients is based on the origin of ingredients, and the safety aspect can assist in the determination of halal status. This study suggested the integration between the origin of ingredients, and the safety and ethical aspects in the evaluation of halal cosmetic to better describe the practical aspect of halal-tayyib in cosmetics. The integration of safety and halal, and ethics and responsibility are suggested to better describe the practical aspect of halal-tayyib in cosmetics.

[Clinical experience in the diagnosis and treatment of aortic stenosis caused by Takayasu arteritis in pediatric patients].

Objective: To analyze the clinical features and summarize the experience on the diagnosis and treatment of aortic stenosis caused by Takayasu arteritis in pediatric patients. Methods: This study was a retrospective study. Five pediatric patients diagnosed as aortic stenosis caused by Takayasu arteritis in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2016 to August 2018 were included. The clinical features, methods of examination, treatment and outcome were analyzed. Results: There were 2 male and 3 female patients in this cohort. The age of onset ranged from 10 to 13 years. The main clinical symptoms were as follows: intermittent claudication and hypertension (5 patients), heart failure (3 patients). Three patients with heart failure were misdiagnosed with dilated cardiomyopathy in other hospitals. Except 1 patient died due to disease aggravation before operation, the other 4 patients received interventional therapy for severe heart failure or refractory hypertension on the basis of hormone anti-inflammatory treatment, including 2 patients treated with aortic balloon dilatation and 2 patients treated with aortic balloon dilatation and stent implantation. In post-operational follow-up, clinical symptoms and laboratory examination values of the 4 patients treated with interventional therapy were significantly improved. Conclusions: The clinical symptoms of pediatric patients with aortic stenosis caused by Takayasu arteritis mainly present with intermittent claudication, hypertension and heart failure. Aortic intervention strategy should be applied for pediatric patients with severe heart failure or refractory hypertension as early as possible.

[Effect of stenting for the proximal atherosclerotic extracranial vertebral artery stenosis].

Objective: To evaluate the effect of stenting for proximal atherosclerotic extracranial vertebral artery stenosis. Methods: A total of 204 proximal atherosclerotic extracranial vertebral artery stenosis patients underwent stent implantation at Fuwai Hospital were enrolled consecutively between August 2007 and June 2014 prospectively. Medical records were collected and the clinical results were obtained through outpatient and telephone follow up. Results: (1) The patients were (64.1±7.9) years old, and 179 were male (87.7%). (2) Stent implantation was performed on 210 proximal atherosclerotic extracranial vertebral artery stenosis lesions with 210 stents (156 on the left, 54 on the right), and 6 patients received both sides stent implantations. Technical success rate was 100%(210/210). The stenosis of the lesions was decreased from (85.1±6.4) % to (6.5±3.2) % after the stent implantation (P<0.01). (3) Three (1.5%) patients experienced transient ischemic attack during the procedure, and two (1.0%) patients suffered from minor posterior circulation ischemic strokes on the 2nd and 10th day after the procedure, respectively. (4)The median follow-up was 1.5 (0.8-2.5) years. Three(1.5%) patients died (two non-vacular deaths, and the other one due to sudden cardiac death). Three (1.5%) patients developed stroke (one case ipsilateral posterior circulation stroke, and two cases unrelated area stroke). Four (2.0%) patients experienced transient ischemic attack. One patient suffered nonfatal myocardial infraction. In-stent restenosis occurred in thirty nine (19.4%) patients, of which fourteen (35.9%) patients were totally occluded and four (10.3%) patients with symptomatic restenosis. Kaplan-Meier survival curve showed that the primary patency rate of the vertebral artery were 85.6%, 78.6%, 72.2% and 64.4% at 1, 2, 3 and 5 years, respectively. Conclusions: Stenting for proximal atherosclerotic extracranial vertebral artery stenosis is safe and feasible, with a good middle to long-term patency rate. However, further trials are required to validate the effective results found in this patients cohort.

Sequential Measurement of Intermodal Variability in Public Transportation PM2.5 and CO Exposure Concentrations.

A sequential measurement method is demonstrated for quantifying the variability in exposure concentration during public transportation. This method was applied in Hong Kong by measuring PM2.5 and CO concentrations along a route connecting 13 transportation-related microenvironments within 3-4 h. The study design takes into account ventilation, proximity to local sources, area-wide air quality, and meteorological conditions. Portable instruments were compacted into a backpack to facilitate measurement under crowded transportation conditions and to quantify personal exposure by sampling at nose level. The route included stops next to three roadside monitors to enable comparison of fixed site and exposure concentrations. PM2.5 exposure concentrations were correlated with the roadside monitors, despite differences in averaging time, detection method, and sampling location. Although highly correlated in temporal trend, PM2.5 concentrations varied significantly among microenvironments, with mean concentration ratios versus roadside monitor ranging from 0.5 for MTR train to 1.3 for bus terminal. Measured inter-run variability provides insight regarding the sample size needed to discriminate between microenvironments with increased statistical significance. The study results illustrate the utility of sequential measurement of microenvironments and policy-relevant insights for exposure mitigation and management.

Comparison of sources of variability in school age children exposure to ambient PM2.5.

School age children are particularly susceptible to exposure to ambient fine particle (PM2.5). To provide insight into factors affecting variability in ambient PM2.5 exposure, distributions of daily PM2.5 exposures for school age children are estimated for four seasons in three climatic zones of the United States using a stochastic microenvironmental exposure model, based on ambient concentration, air exchange rate, penetration factor, deposition rate, census data, meteorological data, and time pattern data. Estimated daily individual exposure varies largely among seasons, regions, and individuals. The mean ratio of ambient exposure to ambient concentration (Ea/Ca) ranges from 0.46 to 0.61 among selected regions and seasons, resulting from differences in air exchange rate. The individual Ea/Ca varies by a factor of 2 to 3 over a 95% frequency range among simulated children, resulting from variability in children's time patterns. These patterns are similar among age groups, but vary with the day of the week and outdoor temperature. Variability in exposure is larger between individuals than between groups. The high end ratio of the Ea/Ca, at the 95th percentile of inter-individual variability, is 30% to 50% higher than the mean Ea/Ca ratio. Results can be used to intepret and adjust exposure errors in epidemiology and to assist in development of exposure mitigation strategies.

RANKL inhibits cell proliferation by regulating MALAT1 expression in a human osteoblastic cell line hFOB 1.19.

Receptor activator of NF—κB ligand (RANKL), a TNF—related protein, is a key factor regulating bone metabolism. It has been well known that RANKL—mediated signaling regulates the formation, activation and survival of osteoclast in normal bone modeling and remodeling, and also plays an important role in a variety of pathologic conditions. However, there is no direct evidence about the effect of RANKL on osteoblast. Herein, we investigated whether RANKL had effect on cell proliferation in a normal human fetal osteoblastic cell line hFOB 1.19. MTT assay showed that RANKL inhibited hFOB 1.19 cells growth in a dose—dependent and time—dependent manner. Importantly, we found that RANKL induced the expression of a lncRNA, MALAT1, for the first time. Knockdown of RANK by siRNA blocked the induction of MALAT1 by RANKL. By infection with MALAT1 siRNA, MALAT1 knockdown reversed RANKL—induced cells growth inhibition and cell cycle arrest. In addition, MALAT1 also regulated OPG expression in hFOB 1.19 cells. In conclusion, RANKL, binding to its receptor RANK, inhibited cell proliferation via MALAT1 upregulation in osteoblast cells in vitro.

Assessment of the effect of population and diary sampling methods on estimation of school-age children exposure to fine particles.

Population and diary sampling methods are employed in exposure models to sample simulated individuals and their daily activity on each simulation day. Different sampling methods may lead to variations in estimated human exposure. In this study, two population sampling methods (stratified-random and random-random) and three diary sampling methods (random resampling, diversity and autocorrelation, and Markov-chain cluster [MCC]) are evaluated. Their impacts on estimated children's exposure to ambient fine particulate matter (PM2.5 ) are quantified via case studies for children in Wake County, NC for July 2002. The estimated mean daily average exposure is 12.9 µg/m(3) for simulated children using the stratified population sampling method, and 12.2 µg/m(3) using the random sampling method. These minor differences are caused by the random sampling among ages within census tracts. Among the three diary sampling methods, there are differences in the estimated number of individuals with multiple days of exposures exceeding a benchmark of concern of 25 µg/m(3) due to differences in how multiday longitudinal diaries are estimated. The MCC method is relatively more conservative. In case studies evaluated here, the MCC method led to 10% higher estimation of the number of individuals with repeated exposures exceeding the benchmark. The comparisons help to identify and contrast the capabilities of each method and to offer insight regarding implications of method choice. Exposure simulation results are robust to the two population sampling methods evaluated, and are sensitive to the choice of method for simulating longitudinal diaries, particularly when analyzing results for specific microenvironments or for exposures exceeding a benchmark of concern.

Comparative analyses of histone H3K9 trimethylations in the heart and spleen of normal humans.

The global features of trimethylations of histone 3 at lysine 9 (H3K9me3) have been well studied in recent years; however, most of these studies were performed in mammalian cell lines. In this study, we generated genome-wide maps of H3K9me3 of the human heart and spleen using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) technology. We examined the global patterns of H3K9me3 in both tissues and found that modifications were closely associated with tissue-specific expression, function, and development. In addition, we found that 169 genes displayed significant H3K9me3 differences between the heart and spleen. Among these genes, 64 were heart-H3K9me3-specific, 87 genes were spleen-H3K9me3-specific, and 18 were shared in both heart- and spleen-H3K9me3. In conclusion, we observed significant differences in H3K9me3 in the heart and spleen, which may help to explain epigenetic differences between these tissues. Such novel findings highlight the significance of H3K9me3 as a potential biomarker or promising target for epigenetic-based disease treatment.

The applied basic research of systemic lupus erythematosus based on the biological omics.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies directed against nuclear self-antigens and circulating immune complexes. This results in damages to various organs or systems, including skin, joints, kidneys and the central nervous system. Clinical manifestations of SLE could be diverse, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures and arthritis. The complicated pathogenesis and varied clinical symptoms of SLE pose great challenges in the diagnosis and monitoring of this disease. Unfortunately, the etiological factors and pathogenesis of SLE are still not completely understood. It is noteworthy that recent advances in our understanding of the biological omics and emerging technologies have been providing new tools in the analyses of SLE, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics and so on. In this article, we summarize our current knowledge in this field for a better understanding of the pathogenesis, diagnosis and treatment for SLE.

Increased serum N-terminal pro-B-type natriuretic peptide and left ventricle diastolic dysfunction in patients with hepatitis C virus infection.

Prior studies demonstrated that patients with hepatitis C virus (HCV) infection had higher plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, which may indicate the presence of a subclinical cardiac dysfunction. However, there are few data regarding the echocardiographic assessment in HCV-infected patients. The objectives of this study were to investigate changes in the left ventricle (LV) with echocardiography and to identify echocardiographic correlates of serum NT-proBNP levels in HCV-infected patients. Ninety HCV-infected patients and 90 age and gender-matched healthy controls were included. The level of serum NT-proBNP was higher in the patient group (P < 0.001). The proportion of patients whose serum NT-proBNP levels were higher than 125 pg/mL was greater than that of controls (15.56%vs 3.33%, P = 0.011). Echocardiography did not show any significant difference of cardiac structural abnormalities between groups. In the patient group, E, E' and E/A were lower, and E/E' was higher. The proportion of patients (13, 14.44%) with impaired diastolic filling (E/A ≤ 0.75; 0.75 < E/A < 1.5 and E/E' ≥ 10) was greater than that of the control group (3, 3.33%; P = 0.018). Simple regression analysis demonstrated a statistically significant linear correlation between NT-proBNP levels and left ventricular diastolic diameter (LVDd) (r = 0.178, P = 0.013), left ventricular posterior wall diastolic thickness (LVPWd) (r = 0.147, P = 0.023) and mitral E/E' (r = 0.414, P = 0.027). Independent correlates of NT-proBNP levels (R(2) = 0.34) were older age (ß' = 0.034, P = 0.011) and E/E' ratio (ß' = 0.026, P = 0.018). In conclusion, the combined analysis of NT-proBNP and echocardiography showed a possible subclinical left ventricular diastolic dysfunction as evidence of a pathogenic link between HCV and CVD.

Characterization of runoff from various urban catchments at different spatial scales in Beijing, China.

In order to investigate the characterization of runoff in storm sewer from various urban catchments, three monitoring systems at different spatial scales have been installed separately. They have been held since July 2010 in urban area of Beijing (China). The monitoring data revealed that chemical oxygen demand (COD), total suspended solids (TSS), total nitrogen (TN), total phosphorus (TP), and NH(3)-N values significantly exceed the Class V surface water quality standard developed by Ministry of Environmental Protection of the People's Republic of China (MEP). A surface solids buildup and wash off model for small watershed was adopted to analyze and discuss the process of a runoff pollutant discharge. More than a half of pollutant parameters presented a good fit to the model. However, a slightly worse-fit to the wash off model appeared in less than half of the data. Due to the influence of sewer sediments, sewer system characteristics, catchment characteristics, and other reasons, first flush was seldom observed in storm sewer runoff from these three survey areas. Meanwhile, the correlation between TSS and any other pollutant was analyzed according to cumulative load of pollutants in runoff events. An event mean concentrations (EMCs) approach was adopted to quantify the pollution of runoff. EMCs of various pollutants in storm sewer runoff between different rainfall events were slightly higher than the typical values observed in similar areas at home and abroad, according to other studies reported in literature. Based on quantitative analysis, it can be concluded that urban non-point source pollution is recognized as the major causes of quality deterioration in the receiving water bodies. This is after the point source pollution has been controlled substantially in Beijing. An integrated strategy, which combines centralized and decentralized control, along with the conditions of meteorology, hydrology, urban planning, existing drainage system, etc., will be an effective and economic approach to urban runoff pollution control.

[A lightweight multiscale target object detection network for melanoma based on attention mechanism manipulation].

OBJECTIVE: To propose a deep learning target detection model AM- YOLO that integrates coordinate attention and efficient attention mechanism. METHODS: Mosaic image enhancement and MixUp mixed-class enhancement were used for image preprocessing. In the target detection model YOLOv5s with One-Stage structure and modified backbone network and neck network, the maximum pooling layer of the spatial pyramid of the backbone network was replaced with a two-dimensional maximum pooling layer, and the coordinate attention mechanism and the efficient channel attention mechanism were integrated into the C3 module and the backbone network of the model, respectively. The improved model was compared with the unmodified YOLOv5s model, YOLOv3 model, YOLOv3-SPP model, and YOLOv3-tiny model for relevant algorithmic indicators in comparative experiments. RESULTS: The AM-YOLO model incorporating coordinate attention and efficient channel attention mechanism effectively improved the accuracy of melanoma recognition with also a reduced size of the model weight. This model showed significantly better performance than other models in terms of precision, recall rate and mean average precision, and its mean average precision for benign and malignant melanoma reached 92.8% and 87.1%, respectively. CONCLUSION: The deep learning-based target object detection algorithm model can be applied in recognition of melanoma targets.

Prevalence, Virulence Genes and Antimicrobial Resistance Profiles of Salmonella Serovars from Retail Beef in Selangor, Malaysia.

The aim of the present study was to investigate the prevalence of Salmonella spp., Salmonella Enteritidis and Salmonella Typhimurium in retail beef from different retail markets of Selangor area, as well as, to assess their pathogenic potential and antimicrobial resistance. A total of 240 retail beef meat samples (chuck = 60; rib = 60; round = 60; sirloin = 60) were randomly collected. The multiplex polymerase chain reaction (mPCR) in combination with the most probable number (MPN) method was employed to detect Salmonella spp., S. Enteritidis and S. Typhimurium in the meat samples. The prevalence of Salmonella spp., S. Enteritidis and S. Typhimurium in 240 beef meat samples were 7.50, 1.25, and 0.83%, respectively. The microbial loads of total Salmonella was found in the range of <3 to 15 MPN/g. Eight different serovars of Salmonella were identified among the 23 isolates, and S. Agona was the predominant serovar (26.09%). Interestingly, all the Salmonella isolates were resistant to penicillin, erythromycin and vancomycin, but the sensitivity was observed for tetracycline, gentamicin and amoxicillin/clavulanic acid. All 23 isolates were resistant to at least three antibiotics. Two S. Typhimurium isolates (8.70%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.56 which shown resistance to nine antibiotics. PCR analysis of virulence genes showed that all Salmonella isolates (100%) were positive for the invA gene. Meanwhile, pefA was only identified in S. Enteritidis and S. Typhimurium. The findings in this study indicate that retail beef products tested were widely contaminated with multi-drug resistant (MDR) Salmonella and various virulence genes are present among the isolated Salmonella serovars.

Comparison of the Microbiological Quality and Safety between Conventional and Organic Vegetables Sold in Malaysia.

Given the remarkable increase of public interest in organic food products, it is indeed critical to evaluate the microbiological risk associated with consumption of fresh organic produce. Organic farming practices including the use of animal manures may increase the risk of microbiological contamination as manure can act as a vehicle for transmission of foodborne pathogens. This study aimed to determine and compare the microbiological status between organic and conventional fresh produce at the retail level in Malaysia. A total of 152 organic and conventional vegetables were purchased at retail markets in Malaysia. Samples were analyzed for mesophilic aerobic bacteria, yeasts and molds, and total coliforms using conventional microbiological methods. Combination methods of most probable number-multiplex polymerase chain reaction (MPN-mPCR) were used to detect and quantify foodborne pathogens, including Escherichia coli O157:H7, Shiga toxin-producing E. coli (STEC), Listeria monocytogenes, Salmonella Typhimurium, and Salmonella Enteritidis. Results indicated that most types of organic and conventional vegetables possessed similar microbial count (P > 0.05) of mesophilic aerobic bacteria, yeasts and molds, and total coliforms. E. coli O157:H7 and S. Typhimurium were not detected in any sample analyzed in this study. Among the 152 samples tested, only the conventional lettuce and organic carrot were tested positive for STEC and S. Enteritidis, respectively. L. monocytogenes were more frequently detected in both organic (9.1%) and conventional vegetables (2.7%) as compared to E. coli O157:H7, S. Typhimurium, and S. Enteritidis. Overall, no trend was shown that either organically or conventionally grown vegetables have posed greater microbiological risks. These findings indicated that one particular type of farming practices would not affect the microbiological profiles of fresh produce. Therefore, regardless of farming methods, all vegetables should be subjected to appropriate post-harvest handling practices from farm to fork to ensure the quality and safety of the fresh produce.

Reactive oxygen species enhances the induction of inducible nitric oxide synthase by sphingomyelinase in RAW264.7 cells.

The sphingomyelin pathway, activated by stimuli, such as inflammatory cytokines, results in the formation of ceramide, a second messenger molecule. The purpose of the present study was to examine the mechanism by which macrophage-type nitric oxide synthase (NOS II) is induced by stimulation of the sphingomyelin pathway. When RAW264.7 cells were incubated with sphingomyelinase (SMase), nitrite production, NOS II activity, and NOS II mRNA were increased in a dose-dependent manner. Sphingosine, dihydrosphingosine, N-acetylsphingosine (C2-ceramide), and N-acylsphingosine (natural ceramide) had no effect on nitrite production, suggesting that signal molecules other than these were concomitantly produced by SMase treatment and required for NOS II induction. We then investigated the possible involvement of intracellular reactive oxygen species (ROS) in gene induction. SMase treatment increased the level of intracellular ROS, as assessed by flow cytometric analysis using a ROS-sensitive dye, dichlorofluorescin diacetate. Antioxidants, such as N-acetyl-l-cysteine and alpha-tocopherol, inhibited gene induction as well as nitrite production by SMase. These results suggest that activation of the sphingomyelin pathway induces gene expression and that the elevated ROS were somehow involved in this process.

p160 Bcr mediates platelet-derived growth factor activation of extracellular signal-regulated kinase in vascular smooth muscle cells.

BACKGROUND: The human Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene, which is causative for chronic myeloblastic leukemia. Because Bcr encodes a serine/threonine protein kinase, we studied its kinase activity and determined the role of Bcr in the PDGF signaling pathway to ERK1/2 activation and DNA synthesis in rat aortic smooth muscle cells (RASMCs). METHODS AND RESULTS: In RASMCs, platelet-derived growth factor-BB (PDGF) stimulated Bcr kinase activity, with a maximum at 1 minute. Because phosphatidylinositol 3'-kinase (PI3-K) is essential for Bcr/Abl leukemogenesis, we evaluated the role of mouse PDGF-beta-receptor binding sites for PI3-K (Y708, Y719) and for phospholipase C-gamma (Y977, Y989) in PDGF-mediated Bcr kinase activation. The mutant PDGF receptor Y708F/Y719F but not Y977F/Y989F showed significantly reduced Bcr kinase activity. To determine the role of Bcr in PDGF-mediated signal transduction events leading to ERK1/2 and its downstream Elk1 transcription activation, wild-type (WT) and kinase-negative (KN) Bcr were transiently expressed in RASMCs. Bcr WT enhanced, whereas Bcr KN inhibited, PDGF-stimulated ERK1/2 and Elk1 transcriptional activity. Overexpression of Bcr also enhanced PDGF-induced Ras/Raf-1 activity and DNA synthesis, but this regulation is independent of the kinase activity of Bcr. Finally, we found that Bcr expression was increased in the neointimal layer after balloon injury of rat carotid artery. CONCLUSIONS: These results demonstrated the importance of Bcr in PDGF-mediated events, such as activation of Ras, Raf-1, ERK1/2, and Elk1, and stimulation of DNA synthesis.

Risk perception is affected by modes of risk presentation among Singaporeans.

INTRODUCTION: Not much is known about how Singaporeans perceive and react to risk presentation. There is no consensus on whether the European Union guidelines for describing the risk of side effects are valid. This study investigated the effect of different modes of risk presentation on how Singaporeans perceive and react to medical risk. Furthermore, we investigated the practical usage of qualitative phrases, the European Union's adjectives in particular, in describing levels of risk. MATERIALS AND METHODS: A hypothetical situation about the risk of side effects of an influenza vaccine was presented in either a probability format (i.e., 5%; n = 42) or a frequency format (i.e., 1 out of 20; n = 43). The 2 versions of questionnaire were handed out in an alternate order to a convenience sample of 47 healthcare professionals and 38 university students. RESULTS: Respondents presented with a "5% risk" were more likely to describe the risk as "uncommon" or "rare", as compared to respondents presented with a risk of "one out of twenty" (P <0.01). Furthermore, the former showed more willingness to accept the influenza vaccine described in the hypothetical situation than in the latter, but this was not statistically different (67% versus 54%; P >0.1). CONCLUSIONS: Modes of risk presentation affect how people perceive risk, even among people who are highly educated.