Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Tse C[original query] |
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Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2023 In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected. |
Monitoring Different Social Media Platforms to Report Unplanned School Closures Due to Wildfires in California, October and December 2017
Buchanan BM , Evans HI , Chukwudebe NP , Duncan EA , Yin J , Adhikari BB , Zhou X , Tse ZTH , Chowell G , Meltzer MI , Fung IC . Disaster Med Public Health Prep 2022 17 1-7 OBJECTIVE: Researchers at the Centers for Disease Control and Prevention monitor unplanned school closure (USC) reports through online systematic searches (OSS) to assist public health emergency responses. We counted the additional reports identified through social media along with OSS to improve USC monitoring. METHODS: Facebook and Twitter data of public-school districts and private schools in counties affected by California wildfires in October and December of 2017 and January of 2018 were retrieved. We computed descriptive statistics and performed multivariable logistic regression for both OSS and social media data. RESULTS: Among the 362 public-school districts in wildfire-affected counties, USCs were identified for 115 (32%) districts, of which OSS identified 104 (90%), Facebook, 59 (52%), and Twitter, 37 (32%). These data correspond to 4622 public schools, among which USCs were identified for 888 (19.2%) schools, of which OSS identified 722 (81.3%), Facebook, 496 (55.9%), and Twitter, 312 (35.1%). Among 1289 private schools, USCs were identified for 104 schools, of which OSS identified 47 (45.2%), Facebook, 67 (64.4%), and Twitter, 29 (27.9%). USC announcements identified via social media, in addition to those via OSS, were 11 public school districts, 166 public schools, and 57 private schools. CONCLUSION: Social media complements OSS as additional resources for USC monitoring during disasters. |
Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants.
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2022 28 (5) 1083-1094 The COVID-19 pandemic has demonstrated a clear need for high-throughput, multiplexed, and sensitive assays for detecting SARS-CoV-2 and other respiratory viruses as well as their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic CARMEN (mCARMEN), that combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel (RVP) to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants. |
Activated CD4+ T cells and CD14hiCD16+ monocytes correlate with antibody response following influenza virus infection in humans
Wong SS , Oshansky CM , Guo XZJ , Ralston J , Wood T , Reynolds GE , Seeds R , Jelley L , Waite B , Jeevan T , Zanin M , Widdowson MA , Huang QS , Thomas PG , Webby RJ , Turner N , Baker M , Grant C , McArthur C , Roberts S , Trenholmes A , Wong C , Taylor S , Thompson M , Gross D , Duque J , Haven K , Aley D , Muponisi P , Chand B , Chen Y , Plewes L , Sawtell F , Lawrence S , Cogcoy R , Smith J , Gravidez F , Ma M , Chamberlin S , Davey K , Knowles T , McLeish JA , Todd A , Bocacao J , Gunn W , Kawakami P , Walker S , Madge R , Moore N , Rahnama F , Qiao H , Tse F , Zibaei M , Korrapadu T , Optland L , Dela Cruz C , The Shivers Investigation Team . Cell Rep Med 2021 2 (4) 100237 The failure to mount an antibody response following viral infection or seroconversion failure is a largely underappreciated and poorly understood phenomenon. Here, we identified immunologic markers associated with robust antibody responses after influenza virus infection in two independent human cohorts, SHIVERS and FLU09, based in Auckland, New Zealand and Memphis, Tennessee, USA, respectively. In the SHIVERS cohort, seroconversion significantly associates with (1) hospitalization, (2) greater numbers of proliferating, activated CD4+ T cells, but not CD8+ T cells, in the periphery during the acute phase of illness, and (3) fewer inflammatory monocytes (CD14hiCD16+) by convalescence. In the FLU09 cohort, fewer CD14hiCD16+ monocytes during early illness in the nasal mucosa were also associated with the generation of influenza-specific mucosal immunoglobulin A (IgA) and IgG antibodies. Our study demonstrates that seroconversion failure after infection is a definable immunological phenomenon, associated with quantifiable cellular markers that can be used to improve diagnostics, vaccine efficacy, and epidemiologic efforts. |
Unplanned closure of public schools in Michigan, 2015-2016: Cross-sectional study on rurality and digital data harvesting
Jackson AM , Mullican LA , Tse ZTH , Yin J , Zhou X , Kumar D , Fung IC . J Sch Health 2020 90 (7) 511-519 BACKGROUND: For pandemic preparedness, researchers used online systematic searches to track unplanned school closures (USCs). We determine if Twitter provides complementary data. METHODS: Twitter handles of Michigan public schools and school districts were identified. All tweets associated with these handles were downloaded. USC-related tweets were identified using 5 keywords. Descriptive statistics and multivariable logistic regression were performed in R. RESULTS: Among 3469 Michigan public schools, 2003 maintained their own active Twitter accounts or belonged to school districts with active Twitter accounts. Of these 2003 schools, in 2015-2016 school year, at least 1 USC announcement was identified for 349 schools via the current method only, 678 schools via Twitter only, and 562 schools via both methods. No USC announcements were identified for 414 schools. Rural schools were less likely than city schools to have active Twitter coverage (adjusted relative risk [adjRR] = 0.3956, 95% confidence interval [CI] 0.3312-0.4671), and to announce USCs on Twitter (adjRR = 0.5692, 95% CI 0.4645-0.6823), but more likely to have USCs identified by the current method (adjRR = 1.4545, 95% CI 1.3545-1.5490). CONCLUSIONS: Each method identified USCs that were missed by the other. Our results suggested that identifying USCs on Twitter is complementary to the current method. |
Using Twitter to Track Unplanned School Closures: Georgia Public Schools, 2015-17.
Ahweyevu JO , Chukwudebe NP , Buchanan BM , Yin J , Adhikari BB , Zhou X , Tse ZTH , Chowell G , Meltzer MI , Fung IC . Disaster Med Public Health Prep 2020 15 (5) 1-5 OBJECTIVES: To aid emergency response, Centers for Disease Control and Prevention (CDC) researchers monitor unplanned school closures (USCs) by conducting online systematic searches (OSS) to identify relevant publicly available reports. We examined the added utility of analyzing Twitter data to improve USC monitoring. METHODS: Georgia public school data were obtained from the National Center for Education Statistics. We identified school and district Twitter accounts with 1 or more tweets ever posted ("active"), and their USC-related tweets in the 2015-16 and 2016-17 school years. CDC researchers provided OSS-identified USC reports. Descriptive statistics, univariate, and multivariable logistic regression were computed. RESULTS: A majority (1,864/2,299) of Georgia public schools had, or were in a district with, active Twitter accounts in 2017. Among these schools, 638 were identified with USCs in 2015-16 (Twitter only, 222; OSS only, 2015; both, 201) and 981 in 2016-17 (Twitter only, 178; OSS only, 107; both, 696). The marginal benefit of adding Twitter as a data source was an increase in the number of schools identified with USCs by 53% (222/416) in 2015-16 and 22% (178/803) in 2016-17. CONCLUSIONS: Policy-makers may wish to consider the potential value of incorporating Twitter into existing USC monitoring systems. |
Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017-2018.
Takashita E , Daniels RS , Fujisaki S , Gregory , Gubareva LV , Huang W , Hurt AC , Lackenby A , Nguyen HT , Pereyaslov D , Roe M , Samaan M , Subbarao K , Tse H , Wang D , Yen H-L , Zhang W , Meijer A . Antiviral Res 2020 175 104718-104718 The global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012-13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for the treatment of influenza virus infection in Japan and the United States. For this annual report, the susceptibilities of influenza viruses to NAIs and baloxavir were analyzed. A total of 15409 viruses, collected by World Health Organization (WHO) recognized National Influenza Centers and other laboratories between May 2017 and May 2018, were assessed for phenotypic NAI susceptibility by five WHO Collaborating Centers (CCs). The 50% inhibitory concentration (IC(50)) was determined for oseltamivir, zanamivir, peramivir and laninamivir. Reduced inhibition (RI) or highly reduced inhibition (HRI) by one or more NAIs was exhibited by 0.8% of viruses tested (n = 122). The frequency of viruses with RI or HRI has remained low since this global analysis began (2012-13: 0.6%; 2013-14: 1.9%; 2014-15: 0.5%; 2015-16: 0.8%; 2016-17: 0.2%). PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23G/K/R, PA A36V, PA A37T, PA I38F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions. Five of them were included in phenotypic baloxavir susceptibility analysis by two WHO CCs and IC(50) values were determined. The PA variant viruses showed 6-17-fold reduced susceptibility to baloxavir. Overall, in the 2017-18 period the frequency of circulating influenza viruses with reduced susceptibility to NAIs or baloxavir was low, but continued monitoring is important. |
One hypervirulent clone, sequence type 283, accounts for a large proportion of invasive Streptococcus agalactiae isolated from humans and diseased tilapia in Southeast Asia.
Barkham T , Zadoks RN , Azmai MNA , Baker S , Bich VTN , Chalker V , Chau ML , Dance D , Deepak RN , van Doorn HR , Gutierrez RA , Holmes MA , Huong LNP , Koh TH , Martins E , Mehershahi K , Newton P , Ng LC , Phuoc NN , Sangwichian O , Sawatwong P , Surin U , Tan TY , Tang WY , Thuy NV , Turner P , Vongsouvath M , Zhang D , Whistler T , Chen SL . PLoS Negl Trop Dis 2019 13 (6) e0007421 BACKGROUND: In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence. Before 2015 ST283 had only been reported from twenty humans in Hong Kong and two in France, and from one fish in Thailand. We hypothesised that ST283 was causing region-wide infection in Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: We performed a literature review, whole genome sequencing on 145 GBS isolates collected from six Southeast Asian countries, and phylogenetic analysis on 7,468 GBS sequences including 227 variants of ST283 from humans and animals. Although almost absent outside Asia, ST283 was found in all invasive Asian collections analysed, from 1995 to 2017. It accounted for 29/38 (76%) human isolates in Lao PDR, 102/139 (73%) in Thailand, 4/13 (31%) in Vietnam, and 167/739 (23%) in Singapore. ST283 and its variants were found in 62/62 (100%) tilapia from 14 outbreak sites in Malaysia and Vietnam, in seven fish species in Singapore markets, and a diseased frog in China. CONCLUSIONS: GBS ST283 is widespread in Southeast Asia, where it accounts for a large proportion of bacteraemic GBS, and causes disease and economic loss in aquaculture. If human ST283 is fishborne, as in the Singapore outbreak, then GBS sepsis in Thailand and Lao PDR is predominantly a foodborne disease. However, whether transmission is from aquaculture to humans, or vice versa, or involves an unidentified reservoir remains unknown. Creation of cross-border collaborations in human and animal health are needed to complete the epidemiological picture. |
How did Ebola information spread on twitter: broadcasting or viral spreading
Liang H , Fung IC , Tse ZTH , Yin J , Chan CH , Pechta LE , Smith BJ , Marquez-Lameda RD , Meltzer MI , Lubell KM , Fu KW . BMC Public Health 2019 19 (1) 438 BACKGROUND: Information and emotions towards public health issues could spread widely through online social networks. Although aggregate metrics on the volume of information diffusion are available, we know little about how information spreads on online social networks. Health information could be transmitted from one to many (i.e. broadcasting) or from a chain of individual to individual (i.e. viral spreading). The aim of this study is to examine the spreading pattern of Ebola information on Twitter and identify influential users regarding Ebola messages. METHODS: Our data was purchased from GNIP. We obtained all Ebola-related tweets posted globally from March 23, 2014 to May 31, 2015. We reconstructed Ebola-related retweeting paths based on Twitter content and the follower-followee relationships. Social network analysis was performed to investigate retweeting patterns. In addition to describing the diffusion structures, we classify users in the network into four categories (i.e., influential user, hidden influential user, disseminator, common user) based on following and retweeting patterns. RESULTS: On average, 91% of the retweets were directly retweeted from the initial message. Moreover, 47.5% of the retweeting paths of the original tweets had a depth of 1 (i.e., from the seed user to its immediate followers). These observations suggested that the broadcasting was more pervasive than viral spreading. We found that influential users and hidden influential users triggered more retweets than disseminators and common users. Disseminators and common users relied more on the viral model for spreading information beyond their immediate followers via influential and hidden influential users. CONCLUSIONS: Broadcasting was the dominant mechanism of information diffusion of a major health event on Twitter. It suggests that public health communicators can work beneficially with influential and hidden influential users to get the message across, because influential and hidden influential users can reach more people that are not following the public health Twitter accounts. Although both influential users and hidden influential users can trigger many retweets, recognizing and using the hidden influential users as the source of information could potentially be a cost-effective communication strategy for public health promotion. However, challenges remain due to uncertain credibility of these hidden influential users. |
Uptake and safety of Hepatitis B vaccination during pregnancy: A Vaccine Safety Datalink study
Groom HC , Irving SA , Koppolu P , Smith N , Vazquez-Benitez G , Kharbanda EO , Daley MF , Donahue JG , Getahun D , Jackson LA , Tse Kawai A , Klein NP , McCarthy NL , Nordin JD , Sukumaran L , Naleway AL . Vaccine 2018 36 (41) 6111-6116 INTRODUCTION: Hepatitis B virus (HBV) infection acquired during pregnancy can pose a risk to the infant at birth that can lead to significant and lifelong morbidity. Hepatitis B vaccine (HepB) is recommended for anyone at increased risk for contracting HBV infection, including pregnant women. Limited data are available on the safety of HepB administration during pregnancy. OBJECTIVES: To assess the frequency of maternal HepB receipt among pregnant women and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. METHODS: We examined a retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live birth outcomes from 2004 through 2015. Eligible pregnancies in women aged 12-55years who were continuously enrolled from 6months pre-pregnancy to 6weeks postpartum in VSD integrated health systems were included. We compared pregnancies with HepB exposure to those with other vaccine exposures, and to those with no vaccine exposures. High-risk conditions for contracting HBV infection were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were also evaluated according to maternal HepB exposure status. RESULTS: Among over 650,000 pregnancies in the study period, HepB was administered at a rate of 2.1 per 1000 pregnancies (n=1399), commonly within the first 5weeks of pregnancy. Less than 3% of the HepB-exposed group had a high-risk ICD-9 code indicating need for HepB; this was similar to the rate among HepB unvaccinated groups. There were no significant associations between HepB exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, low birthweight or small for gestational age infants. CONCLUSIONS: Most women who received maternal HepB did not have high-risk indications for vaccination. No increased risk for the adverse events that were examined were observed among women who received maternal HepB or their offspring. |
High-throughput, simultaneous quantitation of hemoglobin adducts of acrylamide, glycidamide, and ethylene oxide using UHPLC-MS/MS
Yang M , Frame T , Tse C , Vesper HW . J Chromatogr B Analyt Technol Biomed Life Sci 2018 1086 197-205 Ethylene oxide (EO), acrylamide (AA) and glycidamide (GA) exposures are associated with mammary tumors in animals. Currently available information about human exposure to these chemicals is limited creating the need for analytical methods to assess their exposure. We developed a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantitate hemoglobin (Hb) N-terminal valine adducts of AA (HbAA), GA (HbGA), and EO (HbEO) using modified Edman reaction. The limits of detection of this method were 3.9, 4.9 and 12.9 in pmol/g Hb for HbAA, HbGA and HbEO, respectively. The among-day and within-day precision for all analytes determined with three levels of quality control pools ranged from 2.2-13.0% in percent coefficient of variation (%CV). The accuracy determined by standard addition was between 94 and 111% among all analytes. The median HbAA, HbGA and HbEO values in 34 self-reported non-smokers were 64.9, 45.3 and 113.6pmol/g Hb and in 70 self-reported smokers were 127.8, 69.6 and 237.1pmol/g Hb, respectively. HbAA, HbGA, and HbEO were detectable in all samples suggesting that the described method is suitable for measuring hemoglobin adducts of AA, GA and EO in the general population. This high throughput method can process 148 samples in 8h. The HbEO/HbGA ratio appears independent of the HbAA levels in non-smokers and decreases with increasing HbAA concentration in smokers. This new method is suitable for measuring human exposure to AA, GA and EO and can provide further insight into the metabolism of these chemicals in humans. |
Contents, followers, and retweets of the Centers for Disease Control and Prevention's Office of Advanced Molecular Detection (@CDC_AMD) Twitter profile: Cross-sectional study
Fung IC , Jackson AM , Mullican LA , Blankenship EB , Goff ME , Guinn AJ , Saroha N , Tse ZTH . JMIR Public Health Surveill 2018 4 (2) e33 BACKGROUND: The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle's entire contents and all followers. OBJECTIVE: This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. METHODS: Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. RESULTS: Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies' accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD's tweets referred to the Office's website and their current research; 17.6% (135/768) referred to their scientists' publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. CONCLUSIONS: This study confirms CDC health communicators' experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. |
Protecting young children from tobacco smoke exposure: A pilot study of Project Zero Exposure
Rosen L , Guttman N , Myers V , Brown N , Ram A , Hovell M , Breysse P , Rule A , Berkovitch M , Zucker D . Pediatrics 2018 141 S107-s117 BACKGROUND: Tobacco smoke exposure (TSE) harms children, who are often "captive smokers" in their own homes. Project Zero Exposure is a parent-oriented, theory-based intervention designed to reduce child TSE. This paper reports on findings from the pilot study, which was conducted in Israel from 2013 to 2014. METHODS: The intervention consisted of motivational interviews, child biomarker and home air quality feedback, a Web site, a video, and self-help materials. The primary outcome was child TSE as measured by hair nicotine. Secondary outcome measures were air nicotine and particulate matter, parental reports of TSE, parental smoking behavior, and TSE child protection. A single-group pre- and posttest design was used. RESULTS: Twenty-six of the 29 recruited families completed the study. The intervention was feasible to implement and acceptable to participants. Among the 17 children with reliable hair samples at baseline and follow-up, log hair nicotine dropped significantly after the intervention (P = .04), hair nicotine levels decreased in 64.7% of children, and reductions to levels of nonexposed children were observed in 35.3% of children. The number of cigarettes smoked by parents (P = .001) and parent-reported child TSE declined (P = .01). Logistical issues arose with measurement of all objective measures, including air nicotine, which did not decline; home air particulate matter; and hair nicotine. CONCLUSIONS: A program based on motivational interviewing and demonstrating TSE and contamination to parents in a concrete and easily understandable way is a promising approach to protect children from TSE. Further research is needed to enhance current methods of measurement and assess promising interventions. |
Ultraperformance liquid chromatography tandem mass spectrometry method to determine formaldehyde hemoglobin adducts in humans as biomarker for formaldehyde exposure
Yang M , Ospina M , Tse C , Toth S , Caudill SP , Vesper HW . Chem Res Toxicol 2017 30 (8) 1592-1598 Formaldehyde (FA) is an environmental chemical classified as a human carcinogen. It is highly reactive and can bind covalently with hemoglobin (Hb) to produce Hb adducts. Measurement of these Hb adducts provides valuable information about exposure to this chemical. We developed a robust, ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantifying FA-Hb adducts in red blood cells. The method measures the FA-VHLTPEEK peptide after trypic digestion. The peptide is a FA adduct at the N-terminus of the beta chain of human Hb. Method mean (+/-SD) accuracy, determined by recovery in quality control and blank material was 103.2% +/- 8.11. The mean among-day and within-day coefficients of variation determined at three concentration levels (%CV) were 9.2% (range: 7.2-10.2%) and 4.9% (range 3.1-7.3%), respectively. The limit of detection was 3.4 nmol/g Hb. This method was applied to the analysis of 135 human blood samples, and FA-VHLTPEEK was detected in all study samples. FA-VHLTPEEK concentrations were not significantly different between smokers and nonsmokers. This work is the first validated UPLC-MS/MS method in which a FA peptide derived from a FA-Hb adduct could be used to monitor exposure to FA in population studies. |
Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in carbon nanotube-driven tumorigenesis
Luanpitpong S , Wang L , Stueckle TA , Tse W , Chen YC , Rojanasakul Y . Oncotarget 2014 5 (11) 3541-54 Cancer stem cells (CSCs) may represent targets for carcinogenic initiation by chemical and environmental agents. Recent studies have raised a concern over the potential carcinogenicity of carbon nanotubes (CNTs), one of the most commonly used engineered nanomaterials with asbestos-like properties. Here, we show that chronic (6-month) exposure of human lung epithelial cells to single-walled (SW) CNTs at the workplace-relevant concentration induced an emergence of lung CSCs, as indicated by the induction of CSC tumor spheres and side population (SP). These CSCs, which were found to overexpress tumor promoter caveolin-1 (Cav-1), displayed aggressive cancer phenotypes of apoptosis resistance and enhanced cell invasion and migration compared with their non-CSC counterpart. Using gene manipulation strategies, we reveal for the first time that Cav-1 plays an essential role in CSC regulation and aggressiveness of SWCNT-transformed cells partly through p53 dysregulation, consistent with their suggested role by microarray and gene ontology analysis. Cav-1 not only promoted tumorigenesis in a xenograft mouse model but also metastasis of the transformed cells to neighboring tissues. Since CSCs are crucial to the initiation and early development of carcinogenesis, our findings on CSC induction by SWCNTs and Cav-1 could aid in the early detection and risk assessment of the disease. |
Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells
Lohcharoenkal W , Wang L , Stueckle TA , Park J , Tse W , Dinu CZ , Rojanasakul Y . Front Physiol 2014 5 222 Rapid development and deployment of engineered nanomaterials such as carbon nanotubes (CNTs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their long-term effects which have not been well addressed. We demonstrated here that prolonged exposure of human mesothelial cells to single-walled CNT (SWCNT) induced neoplastic-like transformation as indicated by anchorage-independent cell growth and increased cell invasiveness. Such transformation was associated with an up-regulation of H-Ras and activation of ERK1/2. Downregulation of H-Ras by siRNA or inactivation of ERK by chemical inhibitor effectively inhibited the aggressive phenotype of SWCNT-exposed cells. Integrin alpha V and cortactin, but not epithelial-mesenchymal transition (EMT) transcriptional regulators, were up-regulated in the SWCNT-exposed cells, suggesting their role in the aggressive phenotype. Cortactin expression was shown to be controlled by the H-Ras/ERK signaling. Thus, our results indicate a novel role of H-Ras/ERK signaling and cortactin in the aggressive transformation of human mesothelial cells by SWCNT. |
Effect of age on the risk of fever and seizures following immunization with measles-containing vaccines in children
Rowhani-Rahbar A , Fireman B , Lewis E , Nordin J , Naleway A , Jacobsen SJ , Jackson LA , Tse A , Belongia EA , Hambidge SJ , Weintraub E , Baxter R , Klein NP . JAMA Pediatr 2013 167 (12) 1111-7 IMPORTANCE: The first dose of live attenuated measles-containing vaccines is associated with an increased risk of febrile seizures 7 to 10 days following immunization among 12- to 23-month-old children. The combination measles, mumps, rubella, and varicella vaccine is associated with a 2-fold increased risk of febrile seizures 7 to 10 days following immunization compared with the separately administered measles, mumps, and rubella and varicella vaccines. It is unknown whether the magnitude of these increased risks depends on age at immunization. OBJECTIVE: To examine the potential modifying effect of age on the risk of fever and seizures following immunization with measles-containing vaccines. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at 8 Vaccine Safety Datalink sites of a total of 840 348 children 12 to 23 months of age who had received a measles-containing vaccine from 2001 through 2011. EXPOSURES: Any measles-containing vaccines and measles-containing vaccines by type. MAIN OUTCOMES AND MEASURES: Fever and seizure events occurring during a 42-day postimmunization observation period. RESULTS: In the analysis of any measles-containing vaccines, the increased risk of seizures during the 7- to 10-day risk interval, using the remainder of the observation period as the control interval, was significantly greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable risk, 9.5 excess cases per 10 000 doses; 95% CI, 7.6-11.5) than among younger children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess cases per 10 000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization fever was significantly greater among older children than among younger children; however, its attributable risk was not. In the analysis of vaccine type, measles, mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in the risk of fever and 2-fold increase in the risk of seizures compared with measles, mumps, and rubella vaccine administered with or without varicella vaccine in both younger and older children. CONCLUSIONS AND RELEVANCE: Measles-containing vaccines are associated with a lower increased risk of seizures when administered at 12 to 15 months of age. Findings of this study that focused on safety outcomes highlight the importance of timely immunization of children with the first dose of measles-containing vaccines. |
Regulation of apoptosis by Bcl-2 cysteine oxidation in human lung epithelial cells
Luanpitpong S , Chanvorachote P , Stehlik C , Tse W , Callery PS , Wang L , Rojanasakul Y . Mol Biol Cell 2013 24 (6) 858-69 Hydrogen peroxide (H(2)O(2)) is a key mediator of oxidative stress known to be important in various cellular processes including apoptosis. Bcl-2 is an oxidative stress-responsive protein and a key regulator of apoptosis; however, the underlying mechanisms of oxidative regulation of Bcl-2 are not well understood. The present study investigated the direct effect of H(2)O(2) on Bcl-2 cysteine oxidation as a potential mechanism of apoptosis regulation. Exposure of human lung epithelial cells to H(2)O(2) induced apoptosis in concomitant with cysteine oxidation and down-regulation of Bcl-2. Inhibition of Bcl-2 oxidation by antioxidants or by site-directed mutagenesis of Bcl-2 at Cys158 and Cys229 abrogated the effects of H(2)O(2) on Bcl-2 and apoptosis. Immunoprecipitation and confocal microscopic studies showed that Bcl-2 interacts with MAP kinase ERK1/2 to suppress apoptosis and that such interaction is modulated by cysteine oxidation of Bcl-2. H(2)O(2)-induced Bcl-2 cysteine oxidation interferes with Bcl-2 and ERK1/2 interaction. Mutation of the cysteine residues inhibited the disruption of Bcl-2-ERK complex as well as the induction of apoptosis by H(2)O(2). Together, these results demonstrate the critical role of Bcl-2 cysteine oxidation in the regulation of apoptosis through ERK signaling. This new finding reveals crucial redox regulatory mechanisms that control the antiapoptotic function of Bcl-2. |
Effect of nonpayment for preventable infections in U.S. hospitals
Lee GM , Kleinman K , Soumerai SB , Tse A , Cole D , Fridkin SK , Horan T , Platt R , Gay C , Kassler W , Goldmann DA , Jernigan J , Jha AK . N Engl J Med 2012 367 (15) 1428-37 BACKGROUND: In October 2008, the Centers for Medicare and Medicaid Services (CMS) discontinued additional payments for certain hospital-acquired conditions that were deemed preventable. The effect of this policy on rates of health care-associated infections is unknown. METHODS: Using a quasi-experimental design with interrupted time series with comparison series, we examined changes in trends of two health care-associated infections that were targeted by the CMS policy (central catheter-associated bloodstream infections and catheter-associated urinary tract infections) as compared with an outcome that was not targeted by the policy (ventilator-associated pneumonia). Hospitals participating in the National Healthcare Safety Network and reporting data on at least one health care-associated infection before the onset of the policy were eligible to participate. Data from January 2006 through March 2011 were included. We used regression models to measure the effect of the policy on changes in infection rates, adjusting for baseline trends. RESULTS: A total of 398 hospitals or health systems contributed 14,817 to 28,339 hospital unit-months, depending on the type of infection. We observed decreasing secular trends for both targeted and nontargeted infections long before the policy was implemented. There were no significant changes in quarterly rates of central catheter-associated bloodstream infections (incidence-rate ratio in the postimplementation vs. preimplementation period, 1.00; P=0.97), catheter-associated urinary tract infections (incidence-rate ratio, 1.03; P=0.08), or ventilator-associated pneumonia (incidence-rate ratio, 0.99; P=0.52) after the policy implementation. Our findings did not differ for hospitals in states without mandatory reporting, nor did it differ according to the quartile of percentage of Medicare admissions or hospital size, type of ownership, or teaching status. CONCLUSIONS: We found no evidence that the 2008 CMS policy to reduce payments for central catheter-associated bloodstream infections and catheter-associated urinary tract infections had any measurable effect on infection rates in U.S. hospitals. (Funded by the Agency for Healthcare Research and Quality.). |
Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011
Tse A , Tseng HF , Greene SK , Vellozzi C , Lee GM . Vaccine 2012 30 (11) 2024-2031 In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit-risk framework to ensure that population health benefits are maximized. |
Carbon nanotubes induce malignant transformation and tumorigenesis of human lung epithelial cells
Wang L , Luanpitpong S , Castranova V , Tse W , Lu Y , Pongrakhananon V , Rojanasakul Y . Nano Lett 2011 11 (7) 2796-803 Carcinogenicity of carbon nanotubes is a major concern but has not been well addressed due to the lack of experimental models. Here, we show that chronic exposure to single-walled carbon nanotubes causes malignant transformation of human lung epithelial cells. The transformed cells induce tumorigenesis in mice and exhibit an apoptosis resistant phenotype characteristic of cancer cells. This study provides new evidence for carbon nanotube-induced carcinogenesis and indicates the potential role of p53 in the process. |
Disinfection and sterilization of prion-contaminated medical instruments
Belay ED , Schonberger LB , Brown P , Priola SA , Chesebro B , Will RG , Asher DM . Infect Control Hosp Epidemiol 2010 31 (12) 1304-6 In the February 2010 issue of the journal, | under "SHEA Guideline," Rutala and Weber1 | recommended | sterilization options for decontaminating neurosurgical instruments exposed to the infectious agents of transmissible | spongiform encephalopathies (TSE agents; prions). The recommendations of Rutala and Weber1 | are contrary to those | endorsed by many other experts in the field, including authors | of some studies cited in their article. Conflicting TSE decontamination protocols have been proposed in the past because | of concerns about the unusual resistance of infectivity to | conventional sterilization methods, the paucity of appropriate | laboratory and epidemiologic data, and the difficulties associated with conducting inactivation studies more relevant | to clinical settings. To address the inconsistent recommendations, the World Health Organization (WHO), in 1999, | convened an international consultation of prominent prion | disease researchers, including experts in agent inactivation, | biology, and epidemiology.2 | The consultation offered various | options appropriate for hospitals in developed and developing | countries, with a consensus recommendation to inactivate | prions, whenever possible, by means of immersion in 1-2 N | NaOH, followed by heating in a gravity displacement autoclave at 121°C for 30 minutes and cleaning and sterilization | by conventional means. Rutala and Weber's1 | option 1—initially cleaning the instruments and then autoclaving at 134°C | for 18 minutes—was viewed by the WHO consultants as the | least effective procedure and was accompanied by a warning | that it was likely to leave residual infectivity in some circumstances and should be used only in those clinical situations | where limited resources preclude using more stringent | options.2 |
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