Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 42 Records) |
Query Trace: Xiang N[original query] |
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Identification of CP77 as the third orthopoxvirus SAMD9L inhibitor with a unique specificity for a rodent SAMD9L (preprint)
Zhang F , Meng X , Townsend MB , Satheshkumar PS , Xiang Y . bioRxiv 2019 551556 Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but Chinese hamster ovary (CHO) cells are non-permissive for vaccinia virus (VACV). Here, we revealed a species-specific difference in host restriction factor SAMD9L as the cause for the restriction and identified orthopoxvirus CP77 as a unique inhibitor capable of antagonizing Chinese hamster SAMD9L (chSAMD9L). Two known VACV inhibitors of SAMD9 and SAMD9L (SAMD9&L), K1 and C7, can bind human and mouse SAMD9&L, but neither can bind chSAMD9L. CRISPR-Cas9 knockout of chSAMD9L from CHO cells removed the restriction for VACV, while ectopic expression of chSAMD9L imposed the restriction for VACV in a human cell line, demonstrating that chSAMD9L is a potent restriction factor for VACV. Contrary to K1 and C7, cowpox virus CP77 can bind chSAMD9L and rescue VACV replication in cells expressing chSAMD9L, indicating that CP77 is yet another SAMD9L inhibitor but has a unique specificity for chSAMD9L. Binding studies showed that the N-terminal 382 amino acids of CP77 were sufficient for binding chSAMD9L and that both K1 and CP77 target a common internal region of SAMD9L. Growth studies with nearly all OPXV species showed that the ability of OPXVs in antagonizing chSAMD9L correlates with CP77 gene status and that a functional CP77 ortholog was maintained in many OPXVs, including monkeypox virus. Our data suggest that species-specific difference in rodent SAMD9L poses a barrier for cross-species OPXV infection and that OPXVs have evolved three SAMD9L inhibitors with different specificities to overcome this barrier.IMPORTANCE Several OPXV species, including monkeypox virus and cowpox virus, cause zoonotic infection in humans. They are believed to use wild rodents as the reservoir or intermediate hosts, but the host or viral factors that are important for OPXV host range in rodents are unknown. Here, we showed that the abortive replication of several OPXV species in a Chinese hamster cell line was caused by a species-specific difference in the host antiviral factor SAMD9L, indicating that SAMD9L divergence in different rodent species poses a barrier for cross-species OPXV infection. While the Chinese hamster SAMD9L could not be inhibited by two previously identified OPXV inhibitors of human and mouse SAMD9L, it can be inhibited by cowpox virus CP77, indicating that OPXVs encode three SAMD9L inhibitors with different specificity. Our data suggest that OPXV host range in broad rodent species depends on three SAMD9L inhibitors with different specificities. |
Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore
Bassig BA , Shu XO , Sjödin A , Koh WP , Gao YT , Adams-Haduch J , Davis M , Wang R , Xiang YB , Engel LS , Purdue MP , Ji BT , Yang G , Jones RS , Langseth H , Hosgood HD , Grimsrud TK , Seow WJ , Wong JYY , Hu W , Chen D , Zheng W , Yuan JM , Lan Q , Rothman N . Int J Cancer 2020 146 (3) 839-849 Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; p(trend) = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; p(trend) = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association. |
Higher body mass index after intrapartum antibiotic exposure in children persists over 10-years
Sidell MA , Getahun D , Tartof SY , Xiang AH , Sharma AJ , Mukhopadhyay S , Puopolo KM , Schrag SJ , Kunani P , Koebnick C . Pediatr Obes 2023 18 (7) e13035 Exposure to intrapartum antibiotic prophylaxis to reduce perinatal group B streptococcal disease was associated with increased childhood body mass index (BMI) persisting to age 10 years compared to no exposure (Δ BMI at 10 years: vaginal delivery 0.14 kg/m(2) , caesarean 0.40 kg/m(2) ). |
Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 Delta and beyond.
Kwon HJ , Kosikova M , Tang W , Ortega-Rodriguez U , Radvak P , Xiang R , Mercer KE , Muskhelishvili L , Davis K , Ward JM , Kosik I , Holly J , Kang I , Yewdell JW , Plant EP , Chen WH , Shriver MC , Barnes RS , Pasetti MF , Zhou B , Wentworth DE , Xie H . iScience 2022 25 (12) 105507 Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2(nd) dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus in vitro and in vivo. By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3(rd) vaccine dose can boost antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections. |
Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors
Wu BC , Olivia NA , Tembo JM , He YX , Zhang YM , Xue Y , Ye CL , Lv Y , Li WJ , Jiang LY , Huo XX , Sun ZY , Chen ZJ , Qin JC , Li AY , Park CG , Klena JD , Ding HH , Chen T . J Med Microbiol 2021 70 (3) Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors. |
Vaccines work: a reason for celebration and renewed commitment.
Cohen AL , Patel MK , Cherian T . Lancet 2021 397 (10272) 351-353 With policy makers around the world considering how to allocate limited health budgets and individuals considering whether to accept vaccinations for themselves and their children, understanding the impact of vaccination has never been more important to inform those decisions. A modelling study by Xiang Li and colleagues in The Lancet reports that vaccination against ten common vaccine-preventable diseases (VPDs) reduced deaths by nearly half in low-income and middle-income countries between 2000 and 2019.1 Using demographic and vaccine coverage data, the authors compiled and analysed modelled VPD burden and vaccine impact estimates from 16 independent research groups. The main findings highlight the large impact of vaccination and how well the global immunisation community and caregivers have done in vaccinating children. Remarkably, this finding is likely to be an underestimate of the full impact of vaccination, and yet, at the same time, the global community is at risk of losing these gains.2 |
Intrapartum antibiotic exposure and body mass index in children
Koebnick C , Sidell MA , Getahun D , Tartof SY , Rozema E , Taylor B , Xiang AH , Spiller MW , Sharma AJ , Mukhopadhyay S , Puopolo KM , Schrag SJ . Clin Infect Dis 2021 73 (4) e938-e946 BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) reduce a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). METHODS: Retrospective cohort study of infants (n=223,431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For Cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using non-linear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding and childhood antibiotic exposure. RESULTS: In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P<0.0001 for all time points, Δ BMI at age 5 years 0.12 kg/m 2, 95% CI 0.07 to 0.16 kg/m 2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In Cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P<0.05 for 0.7-0.8 years, P<0.0001 for all other time points) compared to other antibiotics (Δ BMI at age 5 years 0.24 kg/m 2, 95% CI 0.14 to 0.34 kg/m 2). Breastfeeding did not modify these associations. CONCLUSION: GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health. |
Update: proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A ).
Smith DB , Izopet J , Nicot F , Simmonds P , Jameel S , Meng XJ , Norder H , Okamoto H , van der Poel WHM , Reuter G , Purdy MA . J Gen Virol 2020 101 (7) 692-698 In this recommendation, we update our 2016 table of reference sequences of subtypes of hepatitis E virus (HEV; species Orthohepevirus A, family Hepeviridae) for which complete genome sequences are available (Smith et al., 2016). This takes into account subsequent publications describing novel viruses and additional proposals for subtype names; there are now eight genotypes and 36 subtypes. Although it remains difficult to define strict criteria for distinguishing between virus subtypes, and is not within the remit of the International Committee on Taxonomy of Viruses (ICTV), the use of agreed reference sequences will bring clarity and stability to researchers, epidemiologists and clinicians working with HEV. |
Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates.
Gladstone RA , Lo SW , Goater R , Yeats C , Taylor B , Hadfield J , Lees JA , Croucher NJ , van Tonder AJ , Bentley LJ , Quah FX , Blaschke AJ , Pershing NL , Byington CL , Balaji V , Hryniewicz W , Sigauque B , Ravikumar KL , Almeida SCG , Ochoa TJ , Ho PL , du Plessis M , Ndlangisa KM , Cornick JE , Kwambana-Adams B , Benisty R , Nzenze SA , Madhi SA , Hawkins PA , Pollard AJ , Everett DB , Antonio M , Dagan R , Klugman KP , von Gottberg A , Metcalf BJ , Li Y , Beall BW , McGee L , Breiman RF , Aanensen DM , Bentley SD . Microb Genom 2020 6 (5) Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here. |
Room acoustic modeling and auralization at an indoor firing range
Murphy WJ , Xiang N . J Acoust Soc Am 2019 146 (5) 3868 Reverberation time measurements were conducted in the 21-lane indoor firing range at Wright Patterson Air Force Base. Long reverberation times resulted in poor speech transmission indices (STI) which required acoustical treatments within the range. After treatment, reverberation times were significantly reduced and STI was dramatically enhanced. Standard Sabine and Eyring models failed to accurately predict the reverberation times. A computer simulation of the range was developed to predict room acoustic conditions and auralize speech performance for perceptual evaluation in the range. |
Lessons from an active surveillance pilot to assess the pneumonia of unknown etiology surveillance system in China, 2016: the need to increase clinician participation in the detection and reporting of emerging respiratory infectious diseases
Xiang N , Song Y , Wang Y , Wu J , Millman AJ , Greene CM , Ding Z , Sun J , Yang W , Guo G , Wang R , Guo P , Ren Z , Gong L , Xu P , Zhou S , Lin D , Ni D , Feng Z , Li Q . BMC Infect Dis 2019 19 (1) 770 BACKGROUND: We sought to assess reporting in China's Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system's detection of respiratory infections of public health significance. METHODS: From February 29-May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians' awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting. |
Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data.
Jenkins MM , Almli LM , Pangilinan F , Chong JX , Blue EE , Shapira SK , White J , McGoldrick D , Smith JD , Mullikin JC , Bean CJ , Nembhard WN , Lou XY , Shaw GM , Romitti PA , Keppler-Noreuil K , Yazdy MM , Kay DM , Carter TC , Olshan AF , Moore KJ , Nascone-Yoder N , Finnell RH , Lupo PJ , Feldkamp ML , Nickerson DA , Bamshad MJ , Brody LC , Reefhuis J . Birth Defects Res 2019 111 (20) 1618-1632 BACKGROUND: The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case-control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens. METHODS: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA. RESULTS: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol. CONCLUSIONS: This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene-environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers. |
Identification of CP77 as the third orthopoxvirus SAMD9 and SAMD9L inhibitor with a unique specificity for a rodent SAMD9L
Zhang F , Meng X , Townsend MB , Satheshkumar PS , Xiang Y . J Virol 2019 93 (12) Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but Chinese hamster ovary (CHO) cells are non-permissive for vaccinia virus (VACV). Here, we revealed a species-specific difference in host restriction factor SAMD9L as the cause for the restriction and identified orthopoxvirus CP77 as a unique inhibitor capable of antagonizing Chinese hamster SAMD9L (chSAMD9L). Two known VACV inhibitors of SAMD9 and SAMD9L (SAMD9&L);, K1 and C7, can bind human and mouse SAMD9&L;, but neither can bind chSAMD9L. CRISPR-Cas9 knockout of chSAMD9L from CHO cells removed the restriction for VACV, while ectopic expression of chSAMD9L imposed the restriction for VACV in a human cell line, demonstrating that chSAMD9L is a potent restriction factor for VACV. Contrary to K1 and C7, cowpox virus CP77 can bind chSAMD9L and rescue VACV replication in cells expressing chSAMD9L, indicating that CP77 is yet another SAMD9L inhibitor but has a unique specificity for chSAMD9L. Binding studies showed that the N-terminal 382 amino acids of CP77 were sufficient for binding chSAMD9L and that both K1 and CP77 target a common internal region of SAMD9L. Growth studies with nearly all OPXV species showed that the ability of OPXVs in antagonizing chSAMD9L correlates with CP77 gene status and that a functional CP77 ortholog was maintained in many OPXVs, including monkeypox virus. Our data suggest that species-specific difference in rodent SAMD9L poses a barrier for cross-species OPXV infection and that OPXVs have evolved three SAMD9&L inhibitors with different specificities to overcome this barrier.IMPORTANCE: Several OPXV species, including monkeypox virus and cowpox virus, cause zoonotic infection in humans. They are believed to use wild rodents as the reservoir or intermediate hosts, but the host or viral factors that are important for OPXV host range in rodents are unknown. Here, we showed that the abortive replication of several OPXV species in a Chinese hamster cell line was caused by a species-specific difference in the host antiviral factor SAMD9L, suggesting that SAMD9L divergence in different rodent species poses a barrier for cross-species OPXV infection. While the Chinese hamster SAMD9L could not be inhibited by two previously identified OPXV inhibitors of human and mouse SAMD9&L;, it can be inhibited by cowpox virus CP77, indicating that OPXVs encode three SAMD9&L inhibitors with different specificity. Our data suggest that OPXV host range in broad rodent species depends on three SAMD9&L inhibitors with different specificities. |
Texting/emailing while driving among high school students in 35 states, United States, 2015
Li L , Shults RA , Andridge RR , Yellman MA , Xiang H , Zhu M . J Adolesc Health 2018 63 (6) 701-708 PURPOSE: Determine the prevalence and explore individual- and state-level factors associated with texting/emailing while driving (TWD) among adolescent drivers in the United States. METHODS: Data from 35 states that administered the 2015 state Youth Risk Behavior Survey were analyzed. We used Poisson regression models with robust error variance to estimate prevalence ratios (PRs) for TWD. RESULTS: Among the 101,397 high school students aged >/= 14 years who had driven a vehicle during the past 30 days, 38% reported TWD at least once. TWD prevalence ranged from 26% in Maryland to 64% in South Dakota. TWD prevalence was higher in states with a lower minimum learner's permit age and in states where a larger percentage of students drove. Multivariable analyses revealed that the likelihood of TWD increased substantially with age, and white students were more likely to engage in TWD than students of all other races/ethnicities. Infrequent seatbelt users were 21% more likely to engage in TWD compared with frequent seatbelt users (adjusted PR=1.21, 95% confidence interval: 1.16-1.26), and students who reported drinking and driving were almost twice as likely to TWD as compared to students who did not (adjusted PR=1.91, 95% confidence interval: 1.79-2.04). CONCLUSIONS: Prevalence of TWD among US high school students varied by more than two-fold across states. TWD prevalence was higher in states with lower minimum learner's permit ages and in states where a larger percentage of students drove. Older age, white race/ethnicity, and other risky driving behaviors were associated with TWD. |
Invasive Streptococcus pneumoniae infection among hospitalized patients in Jingzhou city, China, 2010-2012
Jiang H , Huai Y , Chen H , Uyeki TM , Chen M , Guan X , Liu S , Peng Y , Yang H , Luo J , Zheng J , Huang J , Peng Z , Xiang N , Zhang Y , Klena JD , Hu DJ , Rainey JJ , Huo X , Xiao L , Xing X , Zhan F , Yu H , Varma JK . PLoS One 2018 13 (8) e0201312 BACKGROUND: Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China. METHODS: We conducted surveillance for IPD among children and adults from April 5, 2010 to September 30, 2012, in four major hospitals in Jingzhou City, Hubei Province. We collected demographic, clinical, and outcome data for all enrolled hospitalized patients with severe acute respiratory infection (SARI) or meningitis, and collected blood, urine, and cerebrospinal fluid (CSF) for laboratory testing for Sp infections. Collected data were entered into Epidata software and imported into SPSS for analysis. RESULTS: We enrolled 22,375 patients, including 22,202 (99%) with SARI and 173 (1%) with meningitis. One hundred and eighteen (118, 3%) with either SARI or meningitis were Sp positive, 32 (0.8%) from blood/CSF culture, and 87 (5%) from urine antigen testing. Of those 118 patients, 57% were aged >/=65 years and nearly 100% received antibiotics during hospitalization. None were previously vaccinated with 7-valent pneumococcal conjugate vaccine (PCV 7), 23-valent pneumococcal polysaccharide vaccine, or seasonal influenza vaccine. The main serotypes identified were 14, 12, 3, 1, 19F, 4, 5, 9V, 15 and 18C, corresponding to serotype coverage rates of 42%, 63%, and 77% for PCV7, PCV10, and PCV13, respectively. CONCLUSIONS: Further work is needed to expand access to pneumococcal vaccination in China, both among children and potentially among the elderly, and inappropriate use of antibiotics is a widespread and serious problem in China. |
Additional progress in the development and application of a direct, rapid immunohistochemical test for rabies diagnosis
Rupprecht CE , Xiang Z , Servat A , Franka R , Kirby J , Ertl HCJ . Vet Sci 2018 5 (2) Laboratory-based surveillance is fundamental to effective rabies prevention and control. The direct fluorescent antibody (AB) test (FAT) is the gold standard for rabies diagnosis. Recently, additional tests besides the FAT have been developed, such as the direct rapid immunohistochemical test (DRIT). In this study, our objective was to further refine technical aspects of the DRIT using a combination of two monoclonal ABs (MABs), 502 and 802, conduct additional testing among rabies reference laboratories using a diversity of animal species and rabies virus (RV) variants and compare the potential utility of the DRIT for end users via proficiency testing (PT) against the FAT. Considering the ideal molar ratios of biotin to AB in formulation of the DRIT conjugate, 3.9 was found to be superior to 7.4, for detection of RV antigens in the brain of a naturally infected raccoon. Optimization of the DRIT conjugate may also be dependent upon the apparent choice of specific viral antigens for testing, as a gray fox RV variant reacted less strongly than a raccoon RV variant in determining the working dilution of the MAB cocktail. Using the same MABs and protocol, the DRIT was compared to the FAT using more than 800 samples of mammalian brains, representative of more than 25 taxa, including in excess of 250 animal rabies cases from Europe and North America. Sensitivity was determined at 98% (96(-)100%, 95% CI) and specificity was calculated at 95% (92(-)96%, 95% CI). In a comparison among end users, PT of laboratory personnel resulted in values of 77(-)100% sensitivity and 86-100% specificity. Based upon these and previously reported results, the DRIT appears to be a suitable alternative to the FAT for use in lyssavirus diagnosis. |
Clusters of human infection and human-to-human transmission of avian influenza A(H7N9) virus, 2013-2017
Zhou L , Chen E , Bao C , Xiang N , Wu J , Wu S , Shi J , Wang X , Zheng Y , Zhang Y , Ren R , Greene CM , Havers F , Iuliano AD , Song Y , Li C , Chen T , Wang Y , Li D , Ni D , Zhang Y , Feng Z , Uyeki TM , Li Q . Emerg Infect Dis 2018 24 (2) 397-400 To detect changes in human-to-human transmission of influenza A(H7N9) virus, we analyzed characteristics of 40 clusters of case-patients during 5 epidemics in China in 2013-2017. Similarities in number and size of clusters and proportion of clusters with probable human-to-human transmission across all epidemics suggest no change in human-to-human transmission risk. |
Prevalence of Chlamydia trachomatis-specific antibodies before and after mass drug administration for trachoma in community-wide surveys of four communities in Nepal
Gwyn SE , Xiang L , Kandel RP , Dean D , Gambhir M , Martin DL . Am J Trop Med Hyg 2017 98 (1) 216-220 The target end date for the global elimination of trachoma as a public health problem is 2020. As countries begin the process for submitting their dossier for the validation of elimination of trachoma as a public health problem, strategies for post-validation surveillance must be considered. Seroprevalence of antibodies against antigens from the causative bacteria Chlamydia trachomatis (Ct) in young children has been shown to reflect trachomatous inflammation-follicular (TF) rates in both endemic and previously endemic settings. However, none of these studies has directly compared age seroprevalence in the same communities before and after mass drug administration (MDA) for trachoma. Here we report a marked shift in age seroprevalence curves in four villages in Kapilvastu District, Nepal, before and after MDA. Clinical examinations were performed and blood was taken before (N = 659) and 5 years after (N = 646) MDA. Rates of TF decreased from 17.6% in ≤ 9-year-olds before MDA (N = 52) to 0% in ≤ 9-year-olds (N = 73) after MDA. Positive antibody responses to Ct in the entire population decreased from 82.1% pre-MDA to 35.8% post-MDA, whereas those among ≤ 9-year-olds decreased from 59.6% to 4.1%. These data show that the postintervention decrease in TF was reflected in a drop in anti-Ct antibody responses, suggesting that antibody responses could be useful indicators for post-validation surveillance. |
Clusters of human infections with avian influenza A(H7N9) virus in China, March 2013 to June 2015
Liu B , Havers FP , Zhou L , Zhong H , Wang X , Mao S , Li H , Ren R , Xiang N , Shu Y , Zhou S , Liu F , Chen E , Zhang Y , Widdowson MA , Li Q , Feng Z . J Infect Dis 2017 216 S548-s554 Multiple clusters of human infections with novel avian influenza A(H7N9) virus have occurred since the virus was first identified in spring 2013. However, in many situations it is unclear whether these clusters result from person-to-person transmission or exposure to a common infectious source. We analyzed the possibility of person-to-person transmission in each cluster and developed a framework to assess the likelihood that person-to-person transmission had occurred. We described 21 clusters with 22 infected contact cases that were identified by the Chinese Center for Disease Control and Prevention from March 2013 through June 2015. Based on detailed epidemiological information and the timing of the contact case patients' exposures to infected persons and to poultry during their potential incubation period, we graded the likelihood of person-to-person transmission as probable, possible, or unlikely. We found that person-to-person transmission probably occurred 12 times and possibly occurred 4 times; it was unlikely in 6 clusters. Probable nosocomial transmission is likely to have occurred in 2 clusters. Limited person-to-person transmission is likely to have occurred on multiple occasions since the H7N9 virus was first identified. However, these transmission events represented a small fraction of all identified cases of H7N9 human infection, and sustained person-to-person transmission was not documented. |
Risk factors for influenza A(H7N9) Disease in China, a matched case control study, October 2014 to April 2015
Zhou L , Ren R , Ou J , Kang M , Wang X , Havers F , Huo X , Liu X , Sun Q , He Y , Liu B , Wu S , Wang Y , Sui H , Zhang Y , Tang S , Chang C , Xiang L , Wang D , Zhao S , Zhou S , Chen T , Xiang N , Greene CM , Zhang Y , Shu Y , Feng Z , Li Q . Open Forum Infect Dis 2016 3 (3) ofw182 Background. Human infections with avian influenza A(H7N9) virus have been associated with exposure to poultry and live poultry markets (LPMs). We conducted a case-control study to identify additional and more specific risk factors. Methods. Cases were laboratory-confirmed A(H7N9) infections in persons in China reported from October 1, 2014 to April 30, 2015. Poultry workers, those with insufficient data, and those refusing participation were excluded. We matched up to 4 controls per case by sex, age, and residential community. Using conditional logistic regression, we examined associations between A(H7N9) infection and potential risk factors. Results. Eighty-five cases and 334 controls were enrolled with similar demographic characteristics. Increased risk of A(H7N9) infection was associated with the following: visiting LPMs (adjusted odds ratio [aOR], 6.3; 95% confidence interval [CI], 2.6-15.3), direct contact with live poultry in LPMs (aOR, 4.1; 95% CI, 1.1-15.6), stopping at a live poultry stall when visiting LPMs (aOR, 2.7; 95% CI, 1.1-6.9), raising backyard poultry at home (aOR, 7.7; 95% CI, 2.0-30.5), direct contact with backyard poultry (aOR, 4.9; 95% CI, 1.1-22.1), and having ≥1 chronic disease (aOR, 3.1; 95% CI, 1.5-6.5). Conclusions. Our study identified raising backyard poultry at home as a risk factor for illness with A(H7N9), suggesting the need for enhanced avian influenza surveillance in rural areas. |
Sero-epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013-2014
Xiang N , Bai T , Kang K , Yuan H , Zhou S , Ren R , Li X , Wu J , Deng L , Zeng G , Wang X , Mao S , Shi J , Gao R , Chen T , Zou S , Li D , Havers F , Widdowson MA , Greene CM , Zhang Y , Ni D , Liu X , Li Q , Shu Y . Influenza Other Respir Viruses 2017 11 (2) 170-176 BACKGROUND: The first human infections of novel avian influenza A(H7N9) virus were identified in China in March 2013. Sentinel surveillance systems and contact tracing may not identify mild and asymptomatic human infections of influenza A(H7N9) virus. OBJECTIVES: We assessed the seroprevalence of antibodies to influenza A(H7N9) virus in three populations during the early stages of the epidemic. PATIENTS/METHODS: From March 2013 to May 2014, we collected sera from the general population, poultry workers, and contacts of confirmed infections in nine Chinese provinces reporting human A(H7N9) infections and, for contacts, second sera 2-3 weeks later. We screened for A(H7N9) antibodies by advanced hemagglutination inhibition (HI) assay and tested sera with HI titers ≥20 by modified microneutralization (MN) assay. MN titers ≥20 or fourfold increases in paired sera were considered seropositive. RESULTS: Among general population sera (n=1480), none were seropositive. Among poultry worker sera (n=1866), 28 had HI titers ≥20; two (0.11%, 95% CI: 0.02-0.44) were positive by MN. Among 61 healthcare and 117 non-healthcare contacts' sera, five had HI titers ≥20, and all were negative by MN. There was no seroconversion among 131 paired sera. CONCLUSIONS: There was no evidence of widespread transmission of influenza A(H7N9) virus during March 2013 to May 2014, although A(H7N9) may have caused rare, previously unrecognized infections among poultry workers. Although the findings suggest that there were few undetected cases of influenza A(H7N9) early in the epidemic, it is important to continue monitoring transmission as virus and epidemic evolve. |
Assessing change in avian influenza A(H7N9) virus infections during the fourth epidemic - China, September 2015-August 2016
Xiang N , Li X , Ren R , Wang D , Zhou S , Greene CM , Song Y , Zhou L , Yang L , Davis CT , Zhang Y , Wang Y , Zhao J , Li X , Iuliano AD , Havers F , Olsen SJ , Uyeki TM , Azziz-Baumgartner E , Trock S , Liu B , Sui H , Huang X , Zhang Y , Ni D , Feng Z , Shu Y , Li Q . MMWR Morb Mortal Wkly Rep 2016 65 (49) 1390-1394 Since human infections with avian influenza A(H7N9) virus were first reported by the Chinese Center for Disease Control and Prevention (China CDC) in March 2013, mainland China has experienced four influenza A(H7N9) virus epidemics. Prior investigations demonstrated that age and sex distribution, clinical features, and exposure history of A(H7N9) virus human infections reported during the first three epidemics were similar. In this report, epidemiology and virology data from the most recent, fourth epidemic (September 2015-August 2016) were compared with those from the three earlier epidemics. Whereas age and sex distribution and exposure history in the fourth epidemic were similar to those in the first three epidemics, the fourth epidemic demonstrated a greater proportion of infected persons living in rural areas, a continued spread of the virus to new areas, and a longer epidemic period. The genetic markers of mammalian adaptation and antiviral resistance remained similar across each epidemic, and viruses from the fourth epidemic remained antigenically well matched to current candidate vaccine viruses. Although there is no evidence of increased human-to-human transmissibility of A(H7N9) viruses, the continued geographic spread, identification of novel reassortant viruses, and pandemic potential of the virus underscore the importance of rigorous A(H7N9) virus surveillance and continued risk assessment in China and neighboring countries. |
Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People's Republic of China
Xiang N , Iuliano AD , Zhang Y , Ren R , Geng X , Ye B , Tu W , Li CA , Lv Y , Yang M , Zhao J , Wang Y , Yang F , Zhou L , Liu B , Shu Y , Ni D , Feng Z , Li Q . BMC Infect Dis 2016 16 (1) 734 BACKGROUND: H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation. METHODS: The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation. RESULTS: In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission. CONCLUSION: Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus. |
Proposed reference sequences for hepatitis E virus subtypes.
Smith DB , Simmonds P , Izopet J , Oliveira-Filho EF , Ulrich RG , Johne R , Koenig M , Jameel S , Harrison TJ , Meng XJ , Okamoto H , van der Poel WH , Purdy MA . J Gen Virol 2016 97 (3) 537-542 The nomenclature of hepatitis E virus (HEV) subtypes in the literature is inconsistent and makes comparison of different studies problematic. We provide a table of complete genome reference sequences for each subtype. The criteria for subtype assignment vary between different genotypes and methodologies, and so a conservative pragmatic approach has been favoured. Updates to this table will be posted on the ICTV website (http://talk.ictvonline.org/r.ashx?C). The use of common reference sequences will facilitate communication between researchers and help clarify the epidemiology of this important human pathogen. This subtyping procedure might be adopted for other Orthohepevirus taxa. |
Estimation of hospitalization rate of laboratory confirmed influenza cases in Jingzhou city, Hubei province, 2010-2012
Zheng J , Chen H , Chen M , Huai Y , Jiang H , Xing X , Peng Z , Xiang N , Zhang Y , Liu L , Huang J , Feng L , Guan X , Klena J , Zhan F , Yu H . Zhonghua Liu Xing Bing Xue Za Zhi 2015 36 (3) 222-7 OBJECTIVE: To estimate the hospitalization rate of severe acute respiratory infection (SARI) cases attributable to influenza in Jingzhou city, Hubei province from 2010 to 2012. METHODS: SARI surveillance was conducted at four hospitals in Jingzhou city, Hubei province from 2010 to 2012. Inpatients meeting the SARI case definition and with informed consent were enrolled to collect their demographic information, clinical features, treatment, and disease outcomes, with their respiratory tract specimens collected for PCR test of influenza virus. RESULTS: From April, 2010 to September, 2012, 19 679 SARI cases enrolled were residents of Jingzhou, and nasopharyngeal swab was collected from 18 412 (93.6%) cases of them to test influenza virus and 13.3% were positive for influenza. During the three consecutive 2010-2012 flu seasons, laboratory-confirmed influenza was associated with 102 per 100 000, 132 per 100 000 and 244 per 100 000, respectively. As for the hospitalization rate attributable to specific type/subtype of influenza virus, 48 per 100 000, 30 per 100 000 and 24 per 100 000 were attributable to A (H3N2), A (H1N1) pdm2009, and influenza B, respectively in 2010-2011 season; 42 per 100 000 [A (H3N2)] and 90 per 100 000 (influenza B) in 2011-2012 season; 90 per 100 000 [A (H3N2)] and one per 100 000 [influenza B] from April, 2010 to September, 2012. SARI hospitalization caused by influenza A or B occurred both mainly among children younger than five years old, with the peak in children aged 0.5 year old. CONCLUSION: Influenza could cause a substantial number of hospitalizations and different viral type/subtype result in different hospitalizations over influenza seasons in Jingzhou city, Hubei province. Children less than five years old should be prioritized for influenza vaccination in China. |
Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban Shanghai
Starling AP , Engel LS , Calafat AM , Koutros S , Satagopan JM , Yang G , Matthews CE , Cai Q , Buckley JP , Ji BT , Cai H , Chow WH , Zheng W , Gao YT , Rothman N , Xiang YB , Shu XO . Environ Int 2015 84 94-106 Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient ≥0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population. |
Synthesis, characterization, and bioactivity of carboxylic acid-functionalized titanium dioxide nanobelts
Hamilton RF , Wu N , Xiang C , Li M , Yang F , Wolfarth M , Porter DW , Holian A . Part Fibre Toxicol 2014 11 (1) 43 BACKGROUND: Surface modification strategies to reduce engineered nanomaterial (ENM) bioactivity have been used successfully in carbon nanotubes. This study examined the toxicity and inflammatory potential for two surface modifications (humic acid and carboxylation) on titanium nanobelts (TNB). METHODS: The in vitro exposure models include C57BL/6 alveolar macrophages (AM) and transformed human THP-1 cells exposed to TNB for 24 hrs in culture. Cell death and NLRP3 inflammasome activation (IL-1beta release) were monitored. Short term (4 and 24 hr) in vivo studies in C57BL/6, BALB/c and IL-1R null mice evaluated inflammation and cytokine release, and cytokine release from ex vivo cultured AM. RESULTS: Both in vitro cell models suggest that the humic acid modification does not significantly affect TNB bioactivity, while carboxylation reduced both toxicity and NLRP3 inflammasome activation. In addition, short term in vivo exposures in both C57BL/6 and IL-1R null mouse strains demonstrated decreased markers of inflammation, supporting the in vitro finding that carboxylation is effective in reducing bioactivity. TNB instillations in IL-1R null mice demonstrated the critical role of IL-1beta in initiation of TNB-induced lung inflammation. Neutrophils were completely absent in the lungs of IL-1R null mice instilled with TNB for 24 hrs. However, the cytokine content of the IL-1R null mice lung lavage samples indicated that other inflammatory agents, IL-6 and TNF-alpha were constitutively elevated indicating a potential compensatory inflammatory mechanism in the absence of IL-1 receptors. CONCLUSIONS: Taken together, the data suggests that carboxylation, but not humic acid modification of TNB reduces, but does not totally eliminate bioactivity of TNB, which is consistent with previous studies of other long aspect ratio nanomaterials such as carbon nanotubes. |
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Wang Z , Zhu B , Zhang M , Parikh H , Jia J , Chung CC , Sampson JN , Hoskins JW , Hutchinson A , Burdette L , Ibrahim A , Hautman C , Raj PS , Abnet CC , Adjei AA , Ahlbom A , Albanes D , Allen NE , Ambrosone CB , Aldrich M , Amiano P , Amos C , Andersson U , Andriole G Jr , Andrulis IL , Arici C , Arslan AA , Austin MA , Baris D , Barkauskas DA , Bassig BA , Beane Freeman LE , Berg CD , Berndt SI , Bertazzi PA , Biritwum RB , Black A , Blot W , Boeing H , Boffetta P , Bolton K , Boutron-Ruault MC , Bracci PM , Brennan P , Brinton LA , Brotzman M , Bueno-de-Mesquita HB , Buring JE , Butler MA , Cai Q , Cancel-Tassin G , Canzian F , Cao G , Caporaso NE , Carrato A , Carreon T , Carta A , Chang GC , Chang IS , Chang-Claude J , Che X , Chen CJ , Chen CY , Chen CH , Chen C , Chen KY , Chen YM , Chokkalingam AP , Chu LW , Clavel-Chapelon F , Colditz GA , Colt JS , Conti D , Cook MB , Cortessis VK , Crawford ED , Cussenot O , Davis FG , De Vivo I , Deng X , Ding T , Dinney CP , Di Stefano AL , Diver WR , Duell EJ , Elena JW , Fan JH , Feigelson HS , Feychting M , Figueroa JD , Flanagan AM , Fraumeni JF Jr , Freedman ND , Fridley BL , Fuchs CS , Gago-Dominguez M , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Garcia-Closas R , Gastier-Foster JM , Gaziano JM , Gerhard DS , Giffen CA , Giles GG , Gillanders EM , Giovannucci EL , Goggins M , Gokgoz N , Goldstein AM , Gonzalez C , Gorlick R , Greene MH , Gross M , Grossman HB , Grubb R 3rd , Gu J , Guan P , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Hartge P , Hattinger C , Hayes RB , He Q , Helman L , Henderson BE , Henriksson R , Hoffman-Bolton J , Hohensee C , Holly EA , Hong YC , Hoover RN , Hosgood HD 3rd , Hsiao CF , Hsing AW , Hsiung CA , Hu N , Hu W , Hu Z , Huang MS , Hunter DJ , Inskip PD , Ito H , Jacobs EJ , Jacobs KB , Jenab M , Ji BT , Johansen C , Johansson M , Johnson A , Kaaks R , Kamat AM , Kamineni A , Karagas M , Khanna C , Khaw KT , Kim C , Kim IS , Kim YH , Kim YC , Kim YT , Kang CH , Jung YJ , Kitahara CM , Klein AP , Klein R , Kogevinas M , Koh WP , Kohno T , Kolonel LN , Kooperberg C , Kratz CP , Krogh V , Kunitoh H , Kurtz RC , Kurucu N , Lan Q , Lathrop M , Lau CC , Lecanda F , Lee KM , Lee MP , Le Marchand L , Lerner SP , Li D , Liao LM , Lim WY , Lin D , Lin J , Lindstrom S , Linet MS , Lissowska J , Liu J , Ljungberg B , Lloreta J , Lu D , Ma J , Malats N , Mannisto S , Marina N , Mastrangelo G , Matsuo K , McGlynn KA , McKean-Cowdin R , McNeill LH , McWilliams RR , Melin BS , Meltzer PS , Mensah JE , Miao X , Michaud DS , Mondul AM , Moore LE , Muir K , Niwa S , Olson SH , Orr N , Panico S , Park JY , Patel AV , Patino-Garcia A , Pavanello S , Peeters PH , Peplonska B , Peters U , Petersen GM , Picci P , Pike MC , Porru S , Prescott J , Pu X , Purdue MP , Qiao YL , Rajaraman P , Riboli E , Risch HA , Rodabough RJ , Rothman N , Ruder AM , Ryu JS , Sanson M , Schned A , Schumacher FR , Schwartz AG , Schwartz KL , Schwenn M , Scotlandi K , Seow A , Serra C , Serra M , Sesso HD , Severi G , Shen H , Shen M , Shete S , Shiraishi K , Shu XO , Siddiq A , Sierrasesumaga L , Sierri S , Sihoe AD , Silverman DT , Simon M , Southey MC , Spector L , Spitz M , Stampfer M , Stattin P , Stern MC , Stevens VL , Stolzenberg-Solomon RZ , Stram DO , Strom SS , Su WC , Sund M , Sung SW , Swerdlow A , Tan W , Tanaka H , Tang W , Tang ZZ , Tardon A , Tay E , Taylor PR , Tettey Y , Thomas DM , Tirabosco R , Tjonneland A , Tobias GS , Toro JR , Travis RC , Trichopoulos D , Troisi R , Truelove A , Tsai YH , Tucker MA , Tumino R , Van Den Berg D , Van Den Eeden SK , Vermeulen R , Vineis P , Visvanathan K , Vogel U , Wang C , Wang C , Wang J , Wang SS , Weiderpass E , Weinstein SJ , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolk A , Wolpin BM , Wong MP , Wrensch M , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xiang YB , Xu J , Yang HP , Yang PC , Yatabe Y , Ye Y , Yeboah ED , Yin Z , Ying C , Yu CJ , Yu K , Yuan JM , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Mirabello L , Savage SA , Kraft P , Chanock SJ , Yeager M , Landi MT , Shi J , Chatterjee N , Amundadottir LT . Hum Mol Genet 2014 23 (24) 6616-33 Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. |
Risk factors for influenza A(H7N9) disease - China, 2013
Liu B , Havers F , Chen E , Yuan Z , Yuan H , Ou J , Shang M , Kang K , Liao K , Liu F , Li D , Ding H , Zhou L , Zhu W , Ding F , Zhang P , Wang X , Yao J , Xiang N , Zhou S , Liu X , Song Y , Su H , Wang R , Cai J , Cao Y , Wang X , Bai T , Wang J , Feng Z , Zhang Y , Widdowson MA , Li Q . Clin Infect Dis 2014 59 (6) 787-94 BACKGROUND: The majority of humans cases of novel avian influenza A(H7N9), which emerged in China in spring 2013, report exposure to poultry. However, specific host and exposure risk factors for disease are unknown, yet critical to design prevention measures. METHODS: In April-June 2013, we conducted a case-control study in eight Chinese provinces. Laboratory-confirmed A(H7N9) cases (n=89) were matched on age, sex, and neighborhood to controls (n=339). Subjects completed a questionnaire on medical history and potential exposures, including poultry markets and other poultry exposure. We used conditional logistic regression to calculate matched and adjusted odds ratios for the association of A(H7N9) virus infection with potential risk factors. RESULTS: Fifty-five percent of cases compared with 31% of controls reported any contact with poultry (matched OR [mOR]: 7.8; 95% confidence interval [CI]: 3.3-18.8). 67% of cases compared with 35% of controls visited a live poultry market (mOR: 5.4; CI: 3.0-9.7). Visiting live poultry markets increased risk of infection even after adjusting for poultry contact and other confounders (adjusted OR: 3.4; CI: 1.8-6.7). Backyard poultry were not associated with increased risk; 14% of cases did not report any poultry exposure or market visit. Obesity (mOR: 4.7; CI: 1.8-12.4), chronic obstructive pulmonary disease (mOR: 2.7; CI: 1.1-6.9), and immunosuppressive medications (mOR: 9.0; CI: 1.7-47.2) were associated with A(H7N9) disease. CONCLUSION: Exposures to poultry in markets were associated with A(H7N9) virus infection, even without poultry contact. China should consider permanently closing live poultry markets or aggressively pursuing control measures to prevent spread of this emerging pathogen. |
Characteristics of US health care providers who counsel adolescents on sports and energy drink consumption
Xiang N , Wethington H , Onufrak S , Belay B . Int J Pediatr 2014 2014 987082 OBJECTIVE: To examine the proportion of health care providers who counsel adolescent patients on sports and energy drink (SED) consumption and the association with provider characteristics. METHODS: This is a cross-sectional analysis of a survey of providers who see patients ≤17 years old. The proportion providing regular counseling on sports drinks (SDs), energy drinks (EDs), or both was assessed. Chi-square analyses examined differences in counseling based on provider characteristics. Multivariate logistic regression calculated adjusted odds ratios (aOR) for characteristics independently associated with SED counseling. RESULTS: Overall, 34% of health care providers regularly counseled on both SEDs, with 41% regularly counseling on SDs and 55% regularly counseling on EDs. On adjusted modeling regular SED counseling was associated with the female sex (aOR: 1.44 [95% CI: 1.07-1.93]), high fruit/vegetable intake (aOR: 2.05 [95% CI: 1.54-2.73]), family/general practitioners (aOR: 0.58 [95% CI: 0.41-0.82]) and internists (aOR: 0.37 [95% CI: 0.20-0.70]) versus pediatricians, and group versus individual practices (aOR: 0.59 [95% CI: 0.42-0.84]). Modeling for SD- and ED-specific counseling found similar associations with provider characteristics. CONCLUSION: The prevalence of regular SED counseling is low overall and varies. Provider education on the significance of SED counseling and consumption is important. |
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