Surgical staging of early stage epithelial ovarian cancer: results from the CDC-NPCR ovarian patterns of care study
Cress RD , Bauer K , O'Malley CD , Kahn AR , Schymura MJ , Wike JM , Stewart SL , Leiserowitz GS . Gynecol Oncol 2011 121 (1) 94-9 OBJECTIVES: The objectives of this study were to determine the adequacy of surgical staging performed on surgically treated epithelial ovarian cancer (EOC) patients with apparent early stage disease and to determine if receipt of surgical staging had an influence on survival. METHODS: Detailed surgical staging information was collected from medical records for 721 patients diagnosed between 1998 and 2000 with EOC. Patients resided in California or New York and were identified through population-based cancer registries. RESULTS: Nearly 90% of patients had removal of the omentum and evaluation of bowel serosa and mesentery but only 72% had assessment of retroperitoneal lymph nodes and the majority of patients did not receive biopsies of other peritoneal locations. Only lymph node assessment (as well as node assessment combined with washings and omentectomy) had a statistically significant association with improved survival. The 5-year survival for women with node sampling was 84.2% versus 69.6% for those without this surgical procedure, and patients who did not have lymph node assessment had nearly twice the risk of death as those who did. When patients were stratified by receipt of chemotherapy, lack of node sampling had an effect only on patients who also had no chemotherapy (adjusted HR=2.2, CI=1.0-4.5). CONCLUSIONS: The results of this population-based study confirm the prognostic importance of surgical staging for women with EOC, and the important role of gynecologic oncologists in treating these patients. Adjuvant chemotherapy does not appear to further improve survival for those women who receive adequate surgical staging. |
Trends in the risk for coronary heart disease among adults with diagnosed diabetes in the U.S.: Findings from the National Health and Nutrition Examination Survey, 1999-2008
Ford ES . Diabetes Care 2011 34 (6) 1337-43 OBJECTIVE: Coronary heart disease (CHD) is a major cause of mortality among people with diabetes. The objective of this study was to examine the trend in an estimated 10-year risk for developing CHD among adults with diagnosed diabetes in the U.S. RESEARCH DESIGN AND METHODS: Data from 1,977 adults, aged 30-79 years, with diagnosed diabetes who participated in the National Health and Nutrition Examination Survey from 1999-2000 to 2007-2008 were used. Estimated risk was calculated using risk prediction algorithms from the UK Prospective Diabetes Study (UKPDS), the Atherosclerosis Risk in Communities study, and the Framingham Heart Study. RESULTS: Significant improvements in mean HbA(1c) concentrations, systolic blood pressure, and the ratio of total cholesterol to HDL cholesterol occurred. No significant linear trend for current smoking status was observed. The estimated UKPDS 10-year risk for CHD was 21.1% in 1999-2000 and 16.4% in 2007-2008 (P(linear trend) < 0.001). The risk decreased significantly among men, women, whites, African Americans, and Mexican Americans. CONCLUSIONS: The estimated 10-year risk for CHD among adults with diabetes has improved significantly from 1999-2000 to 2007-2008. Sustained efforts in improving risk factors should further benefit the cardiovascular health of people with diabetes. |
Quantitative assessment of elemental carbon in the lungs of never smokers, cigarette smokers, and coal miners
Saxena RK , McClure ME , Hays MD , Green FH , McPhee LJ , Vallyathan V , Gilmour MI . J Toxicol Environ Health A 2011 74 (11) 706-15 Inhalation exposure to particulates such as cigarette smoke and coal dust is known to contribute to the development of chronic lung disease. The purpose of this study was to estimate the amount of elemental carbon (EC) deposits from autopsied lung samples from cigarette smokers, miners, and control subjects and explore the relationship between EC level, exposure history, and the extent of chronic lung disease. The samples comprised three subgroups representing never smokers (8), chronic cigarette smokers (26), and coal miners (6). Following the dissolution of lung tissue, the extracted EC residue was quantified using a thermal-optical transmission (TOT) carbon analyzer. Mean EC levels in the lungs of the control group were 56.68 +/- 24.86 (SD) mcg/g dry lung weight. Respective mean EC values in lung samples from the smokers and coal miners were 449.56 +/- 320.3 mcg/g and 6678.2 +/- 6162 mcg/g. These values were significantly higher than those obtained from the never-smoker group. EC levels in the lung and pack-years of cigarette smoking correlated significantly, as did EC levels and the severity of small airway disease. This study provides one of the first quantitative assessments of EC in human lungs from populations at high relative risk for the development of chronic lung disease. |
Association between diagnosed diabetes and self-reported cancer among U.S. adults: Findings from the 2009 Behavioral Risk Factor Surveillance System
Li C , Balluz LS , Ford ES , Okoro CA , Tsai J , Zhao G . Diabetes Care 2011 34 (6) 1365-8 OBJECTIVE: To assess the association between diagnosed diabetes and self-reported cancer among U.S. adults. RESEARCH DESIGN AND METHODS: We analyzed data for 397,783 adults who participated in the 2009 Behavioral Risk Factor Surveillance System. RESULTS: After adjustment for potential confounders, diabetic men had higher adjusted prevalence ratios for cancer of the prostate (1.1 [95% CI 1.0-1.3]), colon (1.3 [1.0-1.7]), pancreas (4.6 [1.8-11.7]), rectum (2.2 [1.0-4.7]), urinary bladder (1.7 [1.2-2.2]), and kidney (1.9 [1.2-3.0]) than nondiabetic men (all P < 0.05). Diabetic women had higher adjusted prevalence ratios for cancer of the breast (1.1 [1.0-1.3]) and endometrium (1.6 [1.2-2.0]), and leukemia (2.3 [1.3-4.2]) than nondiabetic women (all P < 0.05). CONCLUSIONS: Our results suggest that diabetic adults have higher prevalences of certain cancers than nondiabetic adults. |
Risk factors for hand, foot, and mouth disease and herpangina and the preventive effect of hand-washing
Ruan F , Yang T , Ma H , Jin Y , Song S , Fontaine RE , Zhu BP . Pediatrics 2011 127 (4) e898-904 BACKGROUND: Hygiene and social distancing are recommended control measures for hand, foot, and mouth disease (HFMD) and herpangina. However, empirical data to support this recommendation are limited. METHODS: During an outbreak of HFMD and herpangina due to infection by the human enterovirus 71, we defined a case as a vesicular papular rash on the hands, feet, buttocks, or oral mucosa and onset from April 30 to June 26, 2008. We selected 176 HFMD and herpangina case-children and a stratified random sample of 201 asymptomatic control-children; frequency matched according to residency status. We administered a questionnaire to the parents about their children's exposures and hygienic behaviors. RESULTS: Risk factors for HFMD and herpangina included playing with neighborhood children (odds ratio [OR]: 11 [95% confidence interval (CI): 6.2-17]), visiting an outpatient clinic for another reason ≤ 1 week before onset (OR: 20 [95% CI: 5.0-88]), and community exposures to crowded places (OR: 7.3 [95% CI: 4.1-13]). By using a score summarizing responses to 4 hand-washing questions, we found that 50% of the case-children and 2.5% of control-children had a poor score of 1 to 3, whereas 12% of the case-children and 78% of control-children had a good score of ≥7 (OR: 0.00069 [95% CI: 0.0022-0.022]) after we adjusted for residency, age, and community exposures by using logistic regression. CONCLUSIONS: Hand-washing by preschool-aged children and their caregivers had a significant protective effect against community-acquired HFMD and herpangina from the human enterovirus 71 infection. |
Seasonal and 2009 pandemic influenza A (H1N1) virus infection during pregnancy: a population-based study of hospitalized cases
Creanga AA , Kamimoto L , Newsome K , D'Mello T , Jamieson DJ , Zotti ME , Arnold KE , Baumbach J , Bennett NM , Farley MM , Gershman K , Kirschke D , Lynfield R , Meek J , Morin C , Reingold A , Ryan P , Schaffner W , Thomas A , Zansky S , Finelli L , Honein MA . Am J Obstet Gynecol 2011 204 S38-45 We sought to describe characteristics of hospitalized reproductive-aged (15-44 years) women with seasonal (2005/2006 through 2008/2009) and 2009 pandemic influenza A (H1N1) virus infection. We used population-based data from the Emerging Infections Program in 10 US states, and compared characteristics of pregnant (n = 150) and nonpregnant (n = 489) seasonal, and pregnant (n = 489) and nonpregnant (n = 1088) pandemic influenza cases using chi(2) and Fisher's exact tests. Pregnant women represented 23.5% and 31.0% of all reproductive-aged women hospitalized for seasonal and pandemic influenza, respectively. Significantly more nonpregnant than pregnant women with seasonal (71.2% vs 36.0%) and pandemic (69.7% vs 31.9%) influenza had an underlying medical condition other than pregnancy. Antiviral treatment was significantly more common with pandemic than seasonal influenza for both pregnant (86.5% vs 24.0%) and nonpregnant (82.0% vs 55.2%) women. Pregnant women comprised a significant proportion of influenza-hospitalized reproductive-aged women, underscoring the importance of influenza vaccination during pregnancy. |
Understanding disparities in HIV infection between black and white MSM in the United States
Oster AM , Wiegand RE , Sionean C , Miles IJ , Thomas PE , Melendez-Morales L , Le BC , Millett GA . AIDS 2011 25 (8) 1103-12 OBJECTIVE: We evaluated several hypotheses for disparities in HIV infection between black and white MSM in the United States, including incarceration, partner HIV status, circumcision, sexual networks, and duration of infectiousness. DESIGN: The 2008 National HIV Behavioral Surveillance System (NHBS), a cross-sectional survey conducted in 21 US cities. METHODS: MSM were interviewed and tested for HIV infection. For MSM not previously diagnosed with HIV infection, we used logistic regression to test associations between newly diagnosed HIV infection and incarceration history, partner HIV status, circumcision status, and sexual networks (older partners, concurrency, and partner risk behaviors). For HIV-infected MSM, we assessed factors related to duration of infectiousness. RESULTS: Among 5183 MSM not previously diagnosed with HIV infection, incarceration history, circumcision status, and sexual networks were not independently associated with HIV infection. Having HIV-infected partners [adjusted odds ratio (AOR) = 1.9, 95% confidence interval (CI) = 1.2-3.0] or partners of unknown status (AOR = 1.4, CI = 1.1-1.7) were associated with HIV infection. Of these two factors, only one was more common among black MSM - having partners of unknown HIV status. Among previously diagnosed HIV-positive MSM, black MSM were less likely to be on antiretroviral therapy (ART). CONCLUSION: Less knowledge of partner HIV status and lower ART use among black MSM may partially explain differences in HIV infection between black and white MSM. Efforts to encourage discussions about HIV status between MSM and their partners and decrease barriers to ART provision among black MSM may decrease transmission. |
Various viral compartments in HIV-1-infected mothers contribute to in utero transmission of HIV-1
Kourtis AP , Amedee AM , Bulterys M , Danner S , Van Dyke R , O'Sullivan MJ , Maupin R , Jamieson DJ . AIDS Res Hum Retroviruses 2011 27 (4) 421-7 Perinatal HIV transmission occurs in utero or intrapartum. The mechanisms and timing of transmission are not clearly understood. To compare the genetic sequences of the V3 envelope region of infant's plasma HIV to that of the mother's plasma, peripheral blood mononuclear cells (PBMC) and vaginal secretions, and correlate with timing of transmission. All 3 infants had a positive HIV PCR in the first days of life, thus classified as in utero infections. In the first mother-infant pair, two different variants were present in the infant, one correlating with maternal PBMC virus and highly homologous to virus from vaginal secretions and the other identical to sequences in maternal plasma. In the second pair, the infant plasma virus was similar to that of maternal PBMC. In the third pair, the cord blood and infant plasma virus were highly similar to maternal vaginal virus. The presence of more than one HIV variant from the maternal blood and from the vaginal compartment in the cord blood of infants presumably infected in utero could point to more than one episode of transmission or, alternatively, to transmission of PBMC virus. |
Prevalence of transmitted HIV drug resistance in Botswana: Lessons learned from the HIVDR-Threshold Survey conducted among women presenting for routine antenatal care as part of the 2007 National Sentinel Survey
Bussmann H , de la Hoz Gomez F , Roels TH , Wester CW , Bodika SM , Moyo S , Taffa N , Anderson MG , Mine M , Bile EC , Yang C , Mphoyakgosi K , Lehotzky EA , Mlotshwa B , Mmelesi M , Seipone K , Makhema MJ , Marlink RG , Novitsky V , Essex M . AIDS Res Hum Retroviruses 2011 27 (4) 365-72 The emergence and spread of transmitted drug resistance (TDR) poses a major threat to the success of the rapidly expanding antiretroviral treatment (ART) programs in resource-limited countries. The World Health Organization recommends the use of the HIV Drug Resistance Threshold Survey (HIVDR-TS) as an affordable means to monitor the presence of TDR in these settings. We report our experiences and results of the 2007 HIVDR-TS in Botswana, a country with one of the longest-existing national public ART programs in Africa. The HIVDR-TS and HIV-1 incidence testing were performed in the two largest national sites as part of the 2007 antenatal Botswana Sentinel Survey. The HIVDR-TS showed no significant drug resistance mutations (TDR less than 5%) in one site. TDR prevalence, however, could not be ascertained at the second site due to low sample size. The agreement between HIVDR-TS eligibility criteria and laboratory-based methodologies (i.e., BED-CEIA and LS-EIA) in identifying recently HIV-1 infected adults was poor. Five years following the establishment of Botswana's public ART program, the prevalence of TDR remains low. The HIVDR-TS methodology has limitations for low-density populations as in Botswana, where the majority of antenatal sites are too small to recruit sufficient numbers of patients. In addition, the eligibility criteria (age <25 years and parity (first pregnancy)) of the HIVDR-TS performed poorly in identifying recent HIV-1 infections in Botswana. An alternative sampling strategy should be considered for the surveillance of HIVDR in Botswana and similar geographic settings. |
Geographic differences in time to culture conversion in liquid media: tuberculosis trials consortium study 28. Culture conversion is delayed in Africa
Mac Kenzie WR , Heilig CM , Bozeman L , Johnson JL , Muzanye G , Dunbar D , Jost KC Jr , Diem L , Metchock B , Eisenach K , Dorman S , Goldberg S . PLoS One 2011 6 (4) e18358 BACKGROUND: Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. METHODS: In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. RESULTS: African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. CONCLUSIONS: Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved. TRIAL REGISTRATION: ClinicalTrials.gov NCT00144417. |
6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial
Samandari T , Agizew TB , Nyirenda S , Tedla Z , Sibanda T , Shang N , Mosimaneotsile B , Motsamai OI , Bozeman L , Davis MK , Talbot EA , Moeti TL , Moffat HJ , Kilmarx PH , Castro KG , Wells CD . Lancet 2011 377 (9777) 1588-98 BACKGROUND: In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. METHODS: In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per muL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. FINDINGS: Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3.4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2.0%) in 1006 allocated to the continued isoniazid group (incidence 1.26% per year vs 0.72%; hazard ratio 0.57, 95% CI 0.33-0.99, p=0.047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0.26, 0.09-0.80, p=0.02), whereas participants who were tuberculin skin test-negative received no significant benefit (0.75, 0.38-1.46, p=0.40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0.50, 95% CI 0.26-0.97). Severe adverse events and death were much the same in the control and continued isoniazid groups. INTERPRETATION: In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. FUNDING: US Centers for Disease Control and Prevention and US Agency for International Development. |
Cluster of oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infections on a hospital ward among immunocompromised patients--North Carolina, 2009
Chen LF , Dailey NJ , Rao AK , Fleischauer AT , Greenwald I , Deyde VM , Moore ZS , Anderson DJ , Duffy J , Gubareva LV , Sexton DJ , Fry AM , Srinivasan A , Wolfe CR . J Infect Dis 2011 203 (6) 838-46 BACKGROUND: Oseltamivir resistance among 2009 pandemic influenza A (H1N1) viruses (pH1N1) is rare. We investigated a cluster of oseltamivir-resistant pH1N1 infections in a hospital ward. METHODS: We reviewed patient records and infection control measures and interviewed health care personnel (HCP) and visitors. Oseltamivir-resistant pH1N1 infections were found with real-time reverse-transcription polymerase chain reaction and pyrosequencing for the H275Y neuraminidase (NA) mutation. We compared hemagglutinin (HA) sequences from clinical samples from the outbreak with those of other surveillance viruses. RESULTS: During the period 6-11 October 2009, 4 immunocompromised patients within a hematology-oncology ward exhibited symptoms of pH1N1 infection. The likely index patient became febrile 8 days after completing a course of oseltamivir; isolation was instituted 9 days after symptom onset. Three other case patients developed symptoms 1, 3, and 5 days after the index patient. Three case patients were located in adjacent rooms. HA and NA sequences from case patients were identical. Twelve HCP and 6 visitors reported influenza symptoms during the study period. No other pH1N1 isolates from the hospital or from throughout the state carried the H275Y mutation. CONCLUSIONS: Geographic proximity, temporal clustering, presence of H275Y mutation, and viral sequence homology confirmed nosocomial transmission of oseltamivir-resistant pH1N1. Diagnostic vigilance and prompt isolation may prevent nosocomial transmission of influenza. |
Comparison of patients hospitalized with pandemic 2009 influenza A (H1N1) virus infection during the first two pandemic waves in Wisconsin
Truelove SA , Chitnis AS , Heffernan RT , Karon AE , Haupt TE , Davis JP . J Infect Dis 2011 203 (6) 828-37 BACKGROUND: Wisconsin was severely affected by pandemic waves of 2009 influenza A H1N1 infection during the period 15 April through 30 August 2009 (wave 1) and 31 August 2009 through 2 January 2010 (wave 2). METHODS: To evaluate differences in epidemiologic features and outcomes during these pandemic waves, we examined prospective surveillance data on Wisconsin residents who were hospitalized ≥ 24 h with or died of pandemic H1N1 infection. RESULTS: Rates of hospitalizations and deaths from pandemic H1N1 infection in Wisconsin increased 4- and 5-fold, respectively, from wave 1 to wave 2; outside Milwaukee, hospitalization and death rates increased 10- and 8-fold, respectively. Hospitalization rates were highest among racial and ethnic minorities and children during wave 1 and increased most during wave 2 among non-Hispanic whites and adults. Times to hospital admission and antiviral treatment improved between waves, but the overall hospital course remained similar, with no change in hospitalization duration, intensive care unit admission, requirement for mechanical ventilation, or mortality. CONCLUSIONS: We report broader geographic spread and marked demographic differences during pandemic wave 2, compared with wave 1, although clinical outcomes were similar. Our findings emphasize the importance of using comprehensive surveillance data to detect changing characteristics and impacts during an influenza pandemic and of vigorously promoting influenza vaccination and other prevention efforts. |
Profit status of home health care agencies and the risk of hospitalization
Decker FH . Popul Health Manag 2011 14 (4) 199-204 We examined the association of profit status and patient hospitalizations in the present-day home health care market, a market that grew substantially in the past decade, with much of that growth attributed to the entry of for-profit agencies. Data from the 2007 National Home and Hospice Care Survey were linked to the risk-adjusted agency-level measure of the percent of home health episodes of care ending in hospitalizations available from the Centers for Medicare and Medicaid Services' (CMS) Home Health Compare Web site. A linear regression model was estimated (n = 510). Control variables included other agency characteristics besides profit status, area hospital bed supply, and state dummy variables to control for state fixed effects. For-profit agencies were more likely than not-for-profit agencies to have a risk of hospitalizations greater than expected after accounting for patient characteristics and model control variables. Attributes of the CMS hospitalization measure are discussed and implications for future research described. |
Insecticide resistance status of Aedes aegypti in 10 localities in Colombia
Ocampo CB , Salazar-Terreros MJ , Mina NJ , McAllister J , Brogdon W . Acta Trop 2011 118 (1) 37-44 Insecticide resistance is one of the major threats to the effectiveness of vector control programs. In order to establish a baseline susceptibility profile of Aedes aegypti in the southwest of Colombia, 10 localities in four Departments (States) were evaluated. Standardized WHO bioassay, CDC bottle bioassay and microplate biochemical assays of non-specific beta-esterase (NSE), mixed function oxidases (MFO) and acetylcholinesterase were used. Cross resistance was evaluated with field collected mosquitoes that underwent selection pressure in the laboratory from DDT, propoxur and lambdacyhalothrin during three alternate generations. Mosquitoes with mortality rates below 80% in bioassays were considered resistant. Insecticide resistance varied geographically. Insecticide resistance was observed in 100% of localities in which mosquitoes were exposed to DDT, bendiocarb and temephos using both assays. WHO bioassays showed susceptibility to pyrethroids in all the localities evaluated, however CDC bottle bioassays showed decreases in susceptibility especially with lambdacyhalothrin. All localities showed susceptibility to the organophosphate malathion. Mosquitoes from eight regions with evidence of resistance to any of the insecticide evaluated were also evaluated biochemically. Mosquitoes from five of these regions had increased levels of NSE and two regions had increased levels of MFO. Increase levels of NSE explain partially the low susceptibility to temephos found in all the localities. However, the biochemical mechanisms evaluated do not explain all the resistance observed. Cross resistance was observed between the DDT-selected strain and lambdacyhalothrin, and between the lambdacyhalothrin-selected strain and propoxur and vice versa. The selected strains do not show changes in the biochemical assays evaluated, therefore the observed cross-resistance suggests different biochemical mechanisms. This study shows that Ae. aegypti from Colombia can develop resistance to most of the insecticide classes in the market. Periodic surveillance of insecticide resistance is necessary in order to maintain effective interventions. This study helped to establish the National Network for the surveillance of the insecticide resistance in Colombia. |
Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children
Casas L , Fernandez MF , Llop S , Guxens M , Ballester F , Olea N , Irurzun MB , Rodriguez LS , Riano I , Tardon A , Vrijheid M , Calafat AM , Sunyer J . Environ Int 2011 37 (5) 858-66 BACKGROUND: Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects. OBJECTIVES: To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project. METHODS: One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols. RESULTS: Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education. CONCLUSIONS: Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class. |
A method for estimating vaccine preventable pediatric influenza pneumonia hospitalizations in developing countries: Thailand as a case study
Dawood FS , Fry AM , Muangchana C , Sanasuttipun W , Baggett HC , Chunsuttiwat S , Maloney SA , Simmerman JM . Vaccine 2011 29 (26) 4416-21 The burden of influenza in children is increasingly appreciated; some middle-income countries are considering support for influenza vaccine programs. To support decision-making, methods to estimate the potential impact of proposed programs are needed. Using Thailand as a case-study, we present a model that uses surveillance data, published vaccine effectiveness estimates, and vaccination coverage assumptions to estimate the impact of influenza vaccination on pediatric influenza pneumonia hospitalizations. Approximately 56,000 influenza pneumonia hospitalizations occur annually among children aged <18 years in Thailand; 23,700 (41%) may be vaccine-preventable. Vaccination of 85% of Thai children aged 7 months-4 years might prevent 30% of all pediatric influenza pneumonia hospitalizations in Thailand. |
Proceedings from the workshop on estimating the contributions of sodium reduction to preventable death
Schmidt SM , Andrews T , Bibbins-Domingo K , Burt V , Cook NR , Ezzati M , Geleijnse JM , Homer J , Joffres M , Keenan NL , Labarthe DR , Law M , Loria CM , Orenstein D , Schooley MW , Sukumar S , Hong Y . CVD Prev Control 2011 6 (2) 35-40 The primary goal of this workshop was to identify the most appropriate method to estimate the potential effect of reduction in sodium consumption on mortality. Difficulty controlling hypertension at the individual level has motivated international, federal, state, and local efforts to identify and implement population-wide strategies to better control this problem; reduction of sodium intake is one such strategy. Published estimates of the impact of sodium consumption on mortality have used different modeling approaches, effect sizes, and levels of sodium consumption, and thus their estimates of preventable deaths averted vary widely, and are not comparable. In response to this problem, the Centers for Disease Control and Prevention's Division for Heart Disease and Stroke Prevention (DHDSP) convened and facilitated a workshop to examine different methods of estimating the effect of sodium reduction on mortality. The panelists agreed that any of the methodologies presented could provide reasonable estimates, and therefore discussion focused on challenges faced by all methods. The panel concluded that future sodium modeling efforts should generate multiple estimates employing the same scenarios and effect sizes while using different modeling techniques; in addition, future efforts should include outcomes other than mortality (morbidity, costs, and quality of life). Varying reductions in sodium should be modeled at the population level over different time intervals. In an effort to better address some of the uncertainties highlighted by this workshop, the panelists are currently considering developing multiple estimates in a collaborative manner to clarify the potential impact of population-based interventions to reduce sodium consumption. |
Findings from the Council of State and Territorial Epidemiologists' 2008 assessment of state reportable and nationally notifiable conditions in the United States and considerations for the future
Jajosky R , Rey A , Park M , Aranas A , Macdonald S , Ferland L . J Public Health Manag Pract 2011 17 (3) 255-264 CONTEXT: The State Reportable Conditions Assessment (SRCA) is an annual assessment of reporting requirements for reportable public health conditions. The Council of State and Territorial Epidemiologists (CSTE) and the Centers for Disease Control and Prevention have gained valuable experience in developing a centralized repository of information about reportable conditions across US states and territories. OBJECTIVE: This study examines the reporting status in states of nationally notifiable conditions used to inform public health and national surveillance initiatives. DESIGN: Conditions included in SRCA are updated annually by using a Web-based tool created by the CSTE. SETTING: SRCA information for 2008 was reported from all US states, 2 cities, and 4 territories. PARTICIPANTS: Respondents included state or territorial epidemiologists (or designees) for reporting jurisdictions. MAIN OUTCOME MEASURE: Conditions were classified as explicitly reportable, implicitly reportable, or not reportable. Results were tabulated to determine reporting statistics for the conditions nationwide. RESULTS: The SRCA included 101 conditions recommended for national notification: 93 (92%) were infectious conditions, and 8 (8%) were other (noninfectious or crosscutting) conditions. Of nationally notifiable infectious conditions, 61 (66%) were explicitly reportable in 90% or more jurisdictions; only 2 (25%) noninfectious or crosscutting nationally notifiable conditions were explicitly reportable in 90% or more jurisdictions. Furthermore, 3 nationally notifiable infectious conditions were explicitly reportable in less than 70% of jurisdictions. CONCLUSIONS: Although most nationally notifiable conditions were explicitly reportable, we found that many of these conditions have implicit reporting authority in states. As notifiable condition surveillance moves toward an informatics-driven approach, automated electronic case-detection systems will need explicit information about what conditions are reportable. Future work should address the feasibility of standardizing the format of reportable disease lists and nomenclature used to facilitate data aggregation and interpretation across states. |
Application of bayesian techniques to model the burden of human salmonellosis attributable to U.S. food commodities at the point of processing: adaptation of a Danish model
Guo C , Hoekstra RM , Schroeder CM , Pires SM , Ong KL , Hartnett E , Naugle A , Harman J , Bennett P , Cieslak P , Scallan E , Rose B , Holt KG , Kissler B , Mbandi E , Roodsari R , Angulo FJ , Cole D . Foodborne Pathog Dis 2011 8 (4) 509-16 Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country. |
An efficient method for generating poxvirus recombinants in the absence of selection.
Rice AD , Gray SA , Li Y , Damon I , Moyer RW . Viruses 2011 3 (3) 217-232 The use of selectable markers (ecogpt) and selection pressures to aid in detection of poxvirus (Vaccinia, VV) recombinants has been implicated in the unintended introduction of second site mutations. We have reinvestigated the use of the helper virus system described by Scheiflinger et al. [1] and adapted by Yao and Evans [2] which produces recombinants at a high frequency in the absence of any selection, at a rate of 6-100%. Our system uses fowlpox virus (FPV) as the infectious helper virus which in infected cells provides the enzymatic apparatus for transcription and replication of a purified, transfected VV genome and for recombination with a second transfected PCR generated DNA fragment. To optimize the system, a PCR DNA fragment was generated that contained poxvirus promoter driven gfp and lacZ genes inserted within the coding sequences of the viral thymidine kinase gene. This PCR fragment was co-transfected together with VV genomic DNA. Recombinant VV was identified by plaquing the mixture on cells non-permissive for FPV and selection of green fluorescent or LacZ positive recombinant vaccinia plaques. The system was optimized using FPV permissive cells (CEF) and non-permissive cells (A549, CV-1) for both the initial infection/transfection and the subsequent selection. Up to 70% of the progeny vaccinia virus contained the gfp/LacZ insertion. In order to test for the presence of FPV/VV intertypic recombinants or other unintended mutations, recombinant wtVV (RwtVV) was regenerated from the gfp/LacZ viruses and evaluated by RFLP analysis and pathogenesis in animals. While all RwtVVs were viable in cell culture, in many of the RwtVV isolates, RFLP differences were noted and while some recombinant viruses exhibited wild type behavior in mice, a wide range of virulence indicative of unintended changes suggests that mutants created by "rescue" systems require careful analysis particularly before use for in vivo studies employing animal models. |
Is injection serosorting occurring among HIV-positive injection drug users? Comparison by injection partner's HIV status
Mizuno Y , Purcell DW , Metsch LR , Gomez CA , Knowlton AR , Latka MH . J Urban Health 2011 88 (6) 1031-43 Research needs to build evidence for the roles that HIV status of injection partners may or may not play in injection risk behaviors of injection drug users (IDUs). Using baseline data collected from a randomized controlled study (INSPIRE) conducted in four cities (Baltimore, Miami, New York, and San Francisco) from 2001 to 2005, we categorized 759 primarily heterosexual HIV-positive IDUs into four groups based on HIV serostatus of drug injection partners. Thirty-two percent of the sample injected exclusively with HIV-positive partners in the past 3 months and more than 60% had risky injection behavior with these partners. Eight percent injected exclusively with HIV-negative partners and 49% injected with any unknown status partners. The remaining 11% reported having both HIV-positive and -negative injection partners, but no partners of unknown HIV status. Riskier injection behavior was found among the group with mixed status partners. The risk among the group with any unknown status partners appeared to be driven by the greater number of injection partners. No major group differences were observed in socio-demographic and psychosocial factors. Our analysis suggests that serosorting appeared to be occurring among some, but not an overwhelming majority of HIV-positive IDUs, and knowledge of HIV status of all injection partners per se did not appear to be as important as knowledge of sexual partner's HIV status in its association with risk behavior. |
Guidelines for the prevention of intravascular catheter-related infections
O'Grady NP , Alexander M , Burns LA , Dellinger EP , Garland J , Heard SO , Lipsett PA , Masur H , Mermel LA , Pearson ML , Raad II , Randolph AG , Rupp ME , Saint S . Clin Infect Dis 2011 52 (9) e162-e193 These guidelines have been developed for healthcare personnel who insert intravascular catheters and for persons responsible for surveillance and control of infections in hospital, outpatient, and home healthcare settings. This report was prepared by a working group comprising members from professional organizations representing the disciplines of critical care medicine, infectious diseases, healthcare infection control, surgery, anesthesiology, interventional radiology, pulmonary medicine, pediatric medicine, and nursing. The working group was led by the Society of Critical Care Medicine (SCCM), in collaboration with the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), Surgical Infection Society (SIS), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), American Society of Critical Care Anesthesiologists (ASCCA), Association for Professionals in Infection Control and Epidemiology (APIC), Infusion Nurses Society (INS), Oncology Nursing Society (ONS), American Society for Parenteral and Enteral Nutrition (ASPEN), Society of Interventional Radiology (SIR), American Academy of Pediatrics (AAP), Pediatric Infectious Diseases Society (PIDS), and the Healthcare Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention (CDC) and is intended to replace the Guideline for Prevention of Intravascular Catheter-Related Infections published in 2002. These guidelines are intended to provide evidence-based recommendations for preventing intravascular catheter-related infections. Major areas of emphasis include 1) educating and training healthcare personnel who insert and maintain catheters; 2) using maximal sterile barrier precautions during central venous catheter insertion; 3) using a > 0.5% chlorhexidine skin preparation with alcohol for antisepsis; 4) avoiding routine replacement of central venous catheters as a strategy to prevent infection; and 5) using antiseptic/antibiotic impregnated short-term central venous catheters and chlorhexidine impregnated sponge dressings if the rate of infection is not decreasing despite adherence to other strategies (i.e, education and training, maximal sterile barrier precautions, and >0.5% chlorhexidine preparations with alcohol for skin antisepsis). These guidelines also emphasize performance improvement by implementing bundled strategies, and documenting and reporting rates of compliance with all components of the bundle as benchmarks for quality assurance and performance improvement. |
PAMPer and tRIGer: ligand-induced activation of RIG-I.
Bowzard JB , Davis WG , Jeisy-Scott V , Ranjan P , Gangappa S , Fujita T , Sambhara S . Trends Biochem Sci 2011 36 (6) 314-9 Retinoic-acid-inducible gene-I (RIG-I) is an important component of the innate immune response to many RNA viruses that limits viral replication until adaptive immunity becomes available to clear the infection. Upon binding to the nucleic acid genomes and replication intermediates of these viruses, RIG-I undergoes a complex activation process that involves post-translational modifications and structural rearrangements. Once activated, RIG-I upregulates well-studied signal transduction pathways that lead to the production of type-I interferons (IFNs) and a large variety of antiviral IFN-stimulated genes. Thus, an effective antiviral response is dependent on the interaction between pathogen-derived ligands and RIG-I. Recent work has begun to clarify the required characteristics of RIG-I activators and is setting the stage for the identification of authentic ligands used during viral infection. |
The Vaccine Safety Datalink: A model for monitoring immunization safety
Baggs J , Gee J , Lewis E , Fowler G , Benson P , Lieu T , Naleway A , Klein NP , Baxter R , Belongia E , Glanz J , Hambidge SJ , Jacobsen SJ , Jackson L , Nordin J , Weintraub E . Pediatrics 2011 127 Suppl 1 S45-53 The Vaccine Safety Datalink (VSD) project is a collaborative project between the Centers for Disease Control and Prevention and 8 managed care organizations (MCOs) in the United States. Established in 1990 to conduct postmarketing evaluations of vaccine safety, the project has created an infrastructure that allows for high-quality research and surveillance. The 8 participating MCOs comprise a large population of 8.8 million members annually (3% of the US population), which enables researchers to conduct studies that assess adverse events after immunization. Each MCO prepares computerized data files by using a standardized data dictionary containing demographic and medical information on its members, such as age and gender, health plan enrollment, vaccinations, hospitalizations, outpatient clinic visits, emergency department visits, urgent care visits, and mortality data, as well as additional birth information (eg, birth weight) when available. Other information sources, such as medical chart review, member surveys, and pharmacy, laboratory, and radiology data, are often used in VSD studies to validate outcomes and vaccination data. Since 2000, the VSD has undergone significant changes including an increase in the number of participating MCOs and enrolled population, changes in data-collection procedures, the creation of near real-time data files, and the development of near real-time postmarketing surveillance for newly licensed vaccines or changes in vaccine recommendations. Recognized as an important resource in vaccine safety, the VSD is working toward increasing transparency through data-sharing and external input. With its recent enhancements, the VSD provides scientific expertise, continues to develop innovative approaches for vaccine-safety research, and may serve as a model for other patient safety collaborative research projects. |
Workplace efforts to promote influenza vaccination among healthcare personnel and their association with uptake during the 2009 pandemic influenza A (H1N1)
Harris K , Maurer J , Black C , Euler G , Kadiyala S . Vaccine 2011 29 (16) 2978-85 BACKGROUND: Survey data suggest that, in a typical year, less than half U.S. healthcare personnel (HCP) are vaccinated for influenza. We measured workplace efforts to promote influenza vaccination among HCP in the U.S. and their association with seasonal and pandemic vaccination during the 2009-10 influenza season. METHODS: Self-reported survey data collected in June 2010 from eligible HCP (n=1714) participating in a nationally representative, online research panel. HCP eligible for participation in the survey were those reporting as patient care providers and/or working in a healthcare setting. The survey measured workplace exposure to vaccination recommendations, vaccination requirements, on-site vaccination, reminders, and/or rewards, and being vaccinated for seasonal or H1N1 influenza. RESULTS: At least two-thirds of HCP were offered worksite influenza vaccination; about one half received reminders; and 10% were required to be vaccinated. Compared to HCP in other work settings, hospital employees were most (p<0.001) likely to be the subject to efforts to promote vaccination. Vaccination requirements were associated with increases in seasonal and pandemic vaccination rates of between 31 and 49% points (p<0.005). On-site vaccination was associated with increases in seasonal and pandemic vaccination of between 13 and 29% points (p<0.05). Reminders and incentives were not associated with vaccination. CONCLUSIONS: Our findings provide empirical support for vaccination requirements as a strategy for increasing influenza vaccination among HCP. Our findings also suggest that making influenza vaccination available to HCP at work could increase uptake and highlight the need to reach beyond hospitals in promoting vaccination among HCP. |
Highly pathogenic (H5N1) avian influenza induces an inflammatory T helper type 1 cytokine response in the chicken
Karpala AJ , Bingham J , Schat KA , Chen LM , Donis RO , Lowenthal JW , Bean AG . J Interferon Cytokine Res 2011 31 (4) 393-400 To better understand the immune response to highly pathogenic avian influenza virus, we compared expression of cytokines in chickens infected with avian influenza virus (A/Vietnam/1203/04) to that in uninfected chickens. Gene expression analyses revealed that influenza disseminated to multiple organs where immune responses could be identified. Among those cytokines influenced by influenza infection were the T helper type (Th)1-associated cytokines interleukin (IL)12 and interferon gamma. In addition, a corresponding downregulation of the intracytoplasmic factor GATA3 was identified, whereas the Th2 cytokines IL4 and IL10 did not appear to be impacted by the infection. The inflammatory cytokine IL6 also appeared to be highly upregulated along with type 1 and type 3 interferon. Together, these data indicate that a strong inflammatory and Th1 response occurs after highly pathogenic avian influenza infection in the chicken that has implications for strategies that target the immune system for improving resistance to avian influenza. |
Newborn bloodspot screening for lysosomal storage disorders.
Zhou H , Fernhoff P , Vogt RF . J Pediatr 2011 159 (1) 7-13 e1 The lysosomal storage disorders (LSD) include some 50 heterogeneous genetic disorders that result from defects in lysosomal function.1 Most LSD are not apparent at birth, but newborn infants with absent or minimal enzyme activity will usually have symptoms in infancy or childhood. Early detection offers the best opportunity for therapeutic intervention to prevent irreversible damage to affected organ systems. High throughput methods to detect LSD by newborn bloodspot screening (NBS) have been developed for Pompe, Fabry, Gaucher, Neimann-Pick A/B, Mucopolysaccharidosis I (MPS I) and Krabbe disorders.2, 3, 4 Recent interest in NBS-LSD in the United States and several other countries has been driven by public advocacy, laboratory advances, and increasing therapeutic options. Currently, three states in the United States are engaged in some type of NBS-LSD, and three other states have passed legislation requiring it. Globally, programs in Austria and Taiwan are conducting NBS-LSD, and laboratory evaluations are ongoing in several other countries. Laboratory development of an NBS test for X-linked adrenoleukodystrophy (X-ALD), a peroxisomal storage disorder, is also underway. |
Serological evaluation of suspected West Nile virus human cases following its introduction during a dengue outbreak in Puerto Rico, 2007
Hunsperger E , Beltran M , Acosta LN , Jordan-Munoz J , Torres J , Luce R , Tomashek KM . Clin Vaccine Immunol 2011 18 (6) 978-83 A laboratory testing algorithm was evaluated to confirm West Nile virus (WNV) infection in human serum following its introduction in Puerto Rico in 2007. This testing algorithm used two standard diagnostic assays, the IgM antibody capture enzyme linked immunosorbent assay (MAC ELISA) and real time reverse transcriptase polymerase chain reaction (RT-PCR), along with two non-conventional assays, the non-structural protein 1 (NS1) ELISA and plaque reduction neutralization test at 90% (PRNT(90)) with IgG depletion for dengue virus (DENV) and WNV. A total of 2321 serum samples from suspected WNV human cases were submitted for testing. Approximately one third (867, 37%) were cross reactive for DENV and WNV by MAC-ELISA and had negative RT-PCR results for both viruses. Of a subset of 43 samples tested, 31 (72%) of these cases were identified as dengue in the PRNT(90) IgG depletion assay and 8 (19%) were positive in the dengue NS1 antigen ELISA. These two assays combined differentiated 36 (84%) of the samples that could not be diagnosed using the standard diagnostic testing methods. |
Laboratory practices for the identification of Shiga toxin-producing Escherichia coli in the United States, FoodNet sites, 2007
Hoefer D , Hurd S , Medus C , Cronquist A , Hanna S , Hatch J , Hayes T , Larson K , Nicholson C , Wymore K , Tobin-D'Angelo M , Strockbine N , Snippes P , Atkinson R , Griffin PM , Gould LH . Foodborne Pathog Dis 2011 8 (4) 555-60 Clinical laboratory practices affect patient care and disease surveillance. It is recommended that laboratories routinely use both culture for Escherichia coli O157 and a method that detects Shiga toxins (Stx) to identify all Stx-producing E. coli (STEC) and that labs send broths or isolates to a public health laboratory. In 2007, we surveyed laboratories serving Foodborne Diseases Active Surveillance Network sites that performed on-site enteric disease diagnostic testing to determine their culture and nonculture-based testing practices for STEC identification. Our goals were to measure changes over time in laboratory practices and to compare reported practices with published recommendations. Overall, 89% of laboratories used only culture-based methods, 7% used only Stx enzyme immunoassay (EIA), and 4% used both Stx EIA and culture-based methods. Only 2% of laboratories reported simultaneous culture for O157 STEC and use of Stx EIA. The proportion that ever used Stx EIA increased from 6% in 2003 to 11% in 2007. The proportion that routinely tested all specimens with at least one method was 66% in 2003 versus 71% in 2007. Reference laboratories were less likely than others to test all specimens routinely by one or more of these methods (48% vs. 73%, p = 0.03). As of 2007, most laboratories complied with recommendations for O157 STEC testing by culture but not with recommendations for detection of non-O157 STEC. The proportion of laboratories that culture stools for O157 STEC has changed little since 2003, whereas testing for Stx has increased. |
Microscale exoglycosidase processing and lectin capture of glycans with phospholipid assisted capillary electrophoresis separations
Archer-Hartmann SA , Sargent LM , Lowry DT , Holland LA . Anal Chem 2011 83 (7) 2740-7 Capillary electrophoresis separations of glycans labeled with 1-aminopyrene-3,6,8-trisulfonic acid were achieved with separation efficiencies ranging from 480,000 to 640,000 theoretical plates in a 60.2 cm, 25 micrometer inner diameter fused silica capillary. Under these separation conditions, the coefficient of variation in peak area is 10%, and if labeling efficiency is estimated at 100%, the limit of detection is 15 fM. The capillary electrophoresis method incorporated phospholipid additives to enhance the separation of glycans with slight differences in hydrodynamic volume. In addition, the phospholipid additives supported the integration of the lectin concanavalin A as well as the enzymes alpha1-2,3 mannosidase or beta1-4 galactosidase to provide structural and compositional information about the glycans subject to separation. The use of in-capillary cleavage of terminal glycan residues with exoglycosidases offers a number of advantages over benchtop enzymatic sequencing, including reduced consumption of analyte, as well as enzyme. These methods were used to evaluate glycans derived from the glycoproteins alpha1-acid glycoprotein, fetuin, and ribonuclease B, as well as from glycoproteins collected from MCF7 cells. |
Molecular basis and structural insight of vascular KATP channel gating by s-glutathionylation
Yang Y , Shi W , Chen X , Cui N , Konduru AS , Shi Y , Trower TC , Zhang S , Jiang C . J Biol Chem 2011 286 (11) 9298-307 The vascular ATP-sensitive K(+) (K(ATP)) channel is targeted by a variety of vasoactive substances, playing an important role in vascular tone regulation. Our recent studies indicate that the vascular K(ATP) channel is inhibited in oxidative stress via S-glutathionylation. Here we show evidence for the molecular basis of the S-glutathionylation and its structural impact on channel gating. By comparing the oxidant responses of the Kir6.1/SUR2B channel with the Kir6.2/SUR2B channel, we found that the Kir6.1 subunit was responsible for oxidant sensitivity. Oxidant screening of Kir6.1-Kir6.2 chimeras demonstrated that the N terminus and transmembrane domains of Kir6.1 were crucial. Systematic mutational analysis revealed three cysteine residues in these domains: Cys(43), Cys(120), and Cys(176). Among them, Cys(176) was prominent, contributing to >80% of the oxidant sensitivity. The Kir6.1-C176A/SUR2B mutant channel, however, remained sensitive to both channel opener and inhibitor, which indicated that Cys(176) is not a general gating site in Kir6.1, in contrast to its counterpart (Cys(166)) in Kir6.2. A protein pull-down assay with biotinylated glutathione ethyl ester showed that mutation of Cys(176) impaired oxidant-induced incorporation of glutathione (GSH) into the Kir6.1 subunit. In contrast to Cys(176), Cys(43) had only a modest contribution to S-glutathionylation, and Cys(120) was modulated by extracellular oxidants but not intracellular GSSG. Simulation modeling of Kir6.1 S-glutathionylation suggested that after incorporation to residue 176, the GSH moiety occupied a space between the slide helix and two transmembrane helices. This prevented the inner transmembrane helix from undergoing conformational changes necessary for channel gating, retaining the channel in its closed state. |
The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling
Mukherjee A , Morosky SA , Delorme-Axford E , Dybdahl-Sissoko N , Oberste MS , Wang T , Coyne CB . PLoS Pathog 2011 7 (3) e1001311 The host innate immune response to viral infections often involves the activation of parallel pattern recognition receptor (PRR) pathways that converge on the induction of type I interferons (IFNs). Several viruses have evolved sophisticated mechanisms to attenuate antiviral host signaling by directly interfering with the activation and/or downstream signaling events associated with PRR signal propagation. Here we show that the 3C(pro) cysteine protease of coxsackievirus B3 (CVB3) cleaves the innate immune adaptor molecules mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF) as a mechanism to escape host immunity. We found that MAVS and TRIF were cleaved in CVB3-infected cells in culture. CVB3-induced cleavage of MAVS and TRIF required the cysteine protease activity of 3C(pro), occurred at specific sites and within specialized domains of each molecule, and inhibited both the type I IFN and apoptotic signaling downstream of these adaptors. 3C(pro)-mediated MAVS cleavage occurred within its proline-rich region, led to its relocalization from the mitochondrial membrane, and ablated its downstream signaling. We further show that 3C(pro) cleaves both the N- and C-terminal domains of TRIF and localizes with TRIF to signalosome complexes within the cytoplasm. Taken together, these data show that CVB3 has evolved a mechanism to suppress host antiviral signal propagation by directly cleaving two key adaptor molecules associated with innate immune recognition. |
Applications of remote sensing and GIS for monitoring of coal fires, mine subsidence, environmental impacts of coal-mine closure and reclamation
Duzgun O , Kunzer C , Karacan CO . Int J Coal Geol 2011 86 (1) 1-2 This Special Issue of the International Journal of Coal Geology is named “Applications of remote sensing and GIS for monitoring of coal fires, mine subsidence, environmental impacts of coal-mine closure and reclamation”. The main aim in this special issue is to promote efficient and effective exploitation of coal resources with the use of remote sensing (RS) and geographical information systems (GIS). In this special issue, a multitude of research studies spanning from coal fire monitoring, coal-fire related greenhouse gas emission estimation, underground-mining related land subsidence mapping, the analyses of chemical changes in lignite mining lakes, pollution monitoring of abandoned mine sites to reclaimed land are addressed by application of RS and GIS. | Worldwide, 40% of electricity generation relies on coal. In addition to electricity generation, coal is extensively used to produce household heat through combustion as well as an important resource for the chemical industry. Even though coal consumption is increasing largely due to the rapid development of emerging economies, worldwide coal supply is predicted to be sufficient for many years as one of the main commodities for energy generation. According to the International Energy Agency (IEA) and the World Coal Association (WCA), the global total hard coal production was 5990 Mt, whereas lignite production was around 913 Mt in 2009. China, the US, India, Australia and Indonesia were the top five hard coal producing countries, with China accounting for about 50% of the global production with 2971 Mt. In lignite mining, Germany ranks first, followed by Canada and India. According to IEA and WCA, the top coal exporters are Australia, Indonesia and Russia, where the leading importers are Japan, China, and South Korea, which is also demonstrating the steep increase in coal consumption. However, the largest coal consumer in the world is also the largest coal producer: China. The energy demand of approximately 1.3 billion people in China, of whom over 40% live in cities, is mainly provided by coal (by as much as 75%). |
MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation.
Crider KS , Zhu JH , Hao L , Yang QH , Yang TP , Gindler J , Maneval DR , Quinlivan EP , Li Z , Bailey LB , Berry RJ . Am J Clin Nutr 2011 93 (6) 1365-72 BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) genotype is associated with modification of disease and risk of neural tube defects. Plasma and red blood cell (RBC) folate and plasma homocysteine concentrations change in response to daily intakes of folic acid supplements, but no large-scale or population-based randomized trials have examined whether the MTHFR genotype modifies the observed response. OBJECTIVE: We sought to determine whether the MTHFR 677C-->T genotype modifies the response to folic acid supplementation during and 3 mo after discontinuation of supplementation. DESIGN: Northern Chinese women of childbearing age were enrolled in a 6-mo supplementation trial of different folic acid doses: 100, 400, and 4000 mcg/d and 4000 mcg/wk. Plasma and RBC folate and plasma homocysteine concentrations were measured at baseline; after 1, 3, and 6 mo of supplementation; and 3 mo after discontinuation of supplementation. MTHFR genotyping was performed to identify a C-->T mutation at position 677 (n = 932). RESULTS: Plasma and RBC folate and homocysteine concentrations were associated with MTHFR genotype throughout the supplementation trial, regardless of folic acid dose. MTHFR TT was associated with lower folate concentrations, and the trend of TT < CC was maintained at even the highest doses. Folic acid doses of 100 mcg/d or 4000 mcg/wk did not reduce high homocysteine concentrations in those with the MTHFR TT genotype. CONCLUSION: MTHFR genotype was an independent predictor of plasma and RBC folate and plasma homocysteine concentrations and did not have a significant interaction with folic acid dose during supplementation. |
Lung tumor production and tissue metal distribution after exposure to manual metal arc-stainless steel welding fume in A/J and C57BL/6J mice
Zeidler-Erdely PC , Battelli LA , Salmen-Muniz R , Li Z , Erdely A , Kashon ML , Simeonova PP , Antonini JM . J Toxicol Environ Health A 2011 74 (11) 728-36 Stainless steel welding produces fumes that contain carcinogenic metals. Therefore, welders may be at risk for the development of lung cancer, but animal data are inadequate in this regard. Our main objective was to examine lung tumor production and histopathological alterations in lung-tumor-susceptible (A/J) and -resistant C57BL/6J (B6) mice exposed to manual metal arc-stainless steel (MMA-SS) welding fume. Male mice were exposed to vehicle or MMA-SS welding fume (20 mg/kg) by pharyngeal aspiration once per month for 4 mo. At 78 wk postexposure, gross tumor counts and histopathological changes were assessed and metal analysis was done on extrapulmonary tissue (aorta, heart, kidney, and liver). At 78 wk postexposure, gross lung tumor multiplicity and incidence were unremarkable in mice exposed to MMA-SS welding fume. Histopathology revealed that only the exposed A/J mice contained minimal amounts of MMA-SS welding fume in the lung and statistically increased lymphoid infiltrates and alveolar macrophages. A significant increase in tumor multiplicity in the A/J strain was observed at 78 wk. Metal analysis of extrapulmonary tissue showed that only the MMA-SS-exposed A/J mice had elevated levels of Cr, Cu, Mn, and Zn in kidney and Cr in liver. In conclusion, this study further supports that MMA-SS welding fume does not produce a significant tumorigenic response in an animal model, but may induce a chronic lung immune response. In addition, long-term extrapulmonary tissue alterations in metals in the susceptible A/J mouse suggest that the adverse effects of this fume might be cumulative. |
Metabolic syndrome and carotid intima media thickness in urban police officers
Hartley TA , Shankar A , Fekedulegn D , Violanti JM , Andrew ME , Knox SS , Burchfiel CM . J Occup Environ Med 2011 53 (5) 553-61 OBJECTIVE: To examine the association between metabolic syndrome (MetSyn) and carotid intima media thickness (IMT) separately in male and female police officers. METHODS: MetSyn was defined using 2005 guidelines. B-mode ultrasound was used to measure mean and maximum (12 and 36 segments) carotid artery thickness. Analysis of covariance was used to compare mean IMT values across individuals categorized by number of MetSyn components. Adjustments were made for age, smoking status, and low-density lipoprotein cholesterol. RESULTS: Among 106 women, the adjusted mean common and maximum(36) carotid IMT were significantly and positively associated with number of MetSyn components. No associations were found in men (n = 304). Adjusted carotid IMT values were inversely associated with low high-density lipoprotein cholesterol and directly with hypertension in women. CONCLUSIONS: Number of MetSyn components was significantly associated with carotid IMT in female but not in male officers. |
Evaluating the protective capacity of two-post ROPS for a seat-belted occupant during a farm tractor overturn
Guan J , Hsiao H , Zwiener JV , Current RS , Lutz TJ , Cantis DM , Powers JR Jr , Newbraugh BH , Spahr JS . J Agric Saf Health 2011 17 (1) 15-32 This study evaluated the effectiveness of a commercial rollover protective structure (ROPS) and size-extended ROPS in protecting a 95th percentile male operator during tractor overturns. Six rear upset tests (commercial ROPS) and ten side upset tests (commercial and size-extended ROPS) were conducted. A 95th percentile instrumented male manikin was used in all tests. Head injury criterion (HIC15), 80 g limit on resultant head acceleration, neck injury criterion (Nij), and peak axial force (extension-compression) were employed to evaluate injury potential. In all rear tests, the manikin's head impact with the ground was within the tolerance limits for head/neck injuries. Based on limited trials in the side tests, the study observed a small to moderate chance of neck injuries under the commercial and size-extended ROPS conditions; the injury risk was not statistically significant between these two test conditions. This study identified a risk of non-fatal injuries for large-size operators in side overturns, although the prevention effectiveness of commercial versus size-extended ROPS cannot be determined without further testing. These findings may have implications for future ROPS designs. |
Evaluation of microwave steam bags for the decontamination of filtering facepiece respirators
Fisher EM , Williams JL , Shaffer RE . PLoS One 2011 6 (4) e18585 Reusing filtering facepiece respirators (FFRs) has been suggested as a strategy to conserve available supplies for home and healthcare environments during an influenza pandemic. For reuse to be possible, used FFRs must be decontaminated before redonning to reduce the risk of virus transmission; however, there are no approved methods for FFR decontamination. An effective method must reduce the microbial threat, maintain the function of the FFR, and present no residual chemical hazard. The method should be readily available, inexpensive and easily implemented by healthcare workers and the general public. Many of the general decontamination protocols used in healthcare and home settings are unable to address all of the desired qualities of an efficient FFR decontamination protocol. The goal of this study is to evaluate the use of two commercially available steam bags, marketed to the public for disinfecting infant feeding equipment, for FFR decontamination. The FFRs were decontaminated with microwave generated steam following the manufacturers' instructions then evaluated for water absorption and filtration efficiency for up to three steam exposures. Water absorption of the FFR was found to be model specific as FFRs constructed with hydrophilic materials absorbed more water. The steam had little effect on FFR performance as filtration efficiency of the treated FFRs remained above 95%. The decontamination efficacy of the steam bag was assessed using bacteriophage MS2 as a surrogate for a pathogenic virus. The tested steam bags were found to be 99.9% effective for inactivating MS2 on FFRs; however, more research is required to determine the effectiveness against respiratory pathogens. |
Health outcomes associated with lung function decline and respiratory symptoms and disease in a community cohort
Baughman P , Marott JL , Lange P , Andrew M , Hnizdo E . COPD 2011 8 (2) 103-13 BACKGROUND: In workplace respiratory disease prevention, a thorough understanding is needed of the relative contributions of lung function loss and respiratory symptoms in predicting adverse health outcomes. METHODS: Copenhagen City Heart Study respiratory data collected at 4 examinations (1976-2003) and morbidity and mortality data were used to investigate these relationships. With 15 or more years of follow-up for a hospital diagnosis of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease (CHD) mortality, and all-cause mortality, risks for these outcomes were estimated in relation to asthma, chronic bronchitis, shortness of breath, and lung function level at examination 2 (1981-1983) or lung function decline established from examinations 1 (1976-1978) to 2 using 4 measures (FEV(1) slope, FEV(1) relative slope, American College of Occupational and Environmental Medicine's Longitudinal Normal Limit [LNL], or a limit of 90 milliliters per year [ml/yr]). These risks were estimated by hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, height-adjusted baseline forced expiratory volume in 1 second (FEV(1)/height(2)), and height. RESULTS: For COPD morbidity, the increasing trend in the HR (95% CI) by quartiles of the FEV(1) slope reached a maximum of 3.77 (2.76-5.15) for males, 6.12 (4.63-8.10) for females, and 4.14 (1.57-10.90) for never-smokers. Significant increasing trends were also observed for mortality, with females at higher risk. CONCLUSION: Lung function decline was associated with increased risk of COPD morbidity and mortality emphasizing the need to monitor lung function change over time in at-risk occupational populations. |
C-reactive protein, interleukin-6, and posttraumatic stress disorder symptomology in urban police officers
McCanlies EC , Araia SK , Joseph PN , Mnatsakanova A , Andrew ME , Burchfiel CM , Violanti JM . Cytokine 2011 55 (1) 74-8 Our aim was to examine the relationship between the level of the inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6), and posttraumatic stress disorder (PTSD) symptomology in a random sample of 115 police officers. CRP was measured in citrated plasma using a particle enhanced immunonepholometric assay and IL-6 was measured in serum with a solid-phase quantitative sandwich ELISA. The presence of high PTSD symptomology was defined as having an Impact of Event Scale score (IES) of ≥26 compared to<26 (low PTSD symptomology). 28% of the officers had high PTSD symptomology. Mean levels of CRP and IL-6 did not differ significantly between officers with high PTSD symptomology and those with low symptomology (CRP: 0.76mg/l vs. 0.97mg/l; IL-6: 2.03pg/ml vs. 1.74pg/ml). We found no association of CRP and IL-6 levels with PTSD symptomology. This study was limited by sample size and its cross-sectional study design. A lack of association may occur if either CRP or IL-6 is elevated only at the onset of PTSD symptomology, or if inflammation is related to specific key components that define PTSD. Further research examining these relationships in a larger population may be worthwhile. |
Dynamic oversight: implementation gaps and challenges
Howard J . J Nanopart Res 2011 13 (4) 1427-1434 Nanotechnology is touted as a transformative technology in that it is predicted to improve many aspects of human life. There are hundreds of products in the market that utilize nanostructures in their design, such as composite materials made out of carbon or metal oxides. Potential risks to consumers, to the environment, and to workers from the most common passive nanomaterial - carbon nanotubes - are emerging through scientific research. Newer more active nanostructures - such as cancer therapies and targeted drug systems - are also increasing in use and are raising similar risk concerns. Governing the risks to workers is the subject of this commentary. The Occupational Safety and Health Act of 1970 grants the Occupational Safety and Health Administration the legal authority to set occupational health standards to insure that no worker suffers material impairment of health from work. However, setting a standard to protect workers from nanotechnology risks may occur some time in the future because the risks to workers have not been well characterized scientifically. Alternative risk governances - such as dynamic oversight through stakeholder partnerships, soft law approaches, and national adoption of international consensus standards - are evaluated in this article. |
Trends by age in youth physical activity: Youth Media Campaign Longitudinal Survey
Wall MI , Carlson SA , Stein AD , Lee SM , Fulton JE . Med Sci Sports Exerc 2011 43 (11) 2140-7 PURPOSE: To characterize longitudinal age trajectories across 5 years in prevalence of free-time and organized physical activity participation among U.S. youth, by sex, race, and parental education. METHODS: Study participants were a nationally representative sample of youth, 9-13 years old in 2002, who participated in the Centers for Disease Control and Prevention's Youth Media Campaign Longitudinal Survey. Baseline data were collected in 2002. Attrition over the next four years resulted in an overall response rate of 23% by 2006 (n=1,623). The survey collected information concerning respondents' frequency of participation in free-time and organized physical activities outside of school. Organized activities were defined as activities involving a coach, instructor, or other leader. Orthogonal polynomial contrasts were used to test for linear and quadratic trends in respondents' participation free-time and organized physical activity sessions during the previous 7 days over ages 9-17. Pairwise t-tests were used to determine whether age-specific estimates of participation rates differed significantly by sex, race, and parental education level. RESULTS: Free-time physical activity participation prevalence declined linearly from ages 9 to 17 in both sexes but also demonstrated a quadratic trajectory in boys, peaking at age 13. Organized physical activity demonstrated a quadratic trajectory and declined most notably after age 14 in both sexes. Free-time physical activity participation was lower in girls compared to boys between ages 12-16 (difference range: 12-17 percentage points). Both non-white youth and those with less educated parents had lower organized physical activity participation at most ages (difference range: 15-29 percentage points). CONCLUSION: Free-time and organized physical activity exhibit different trajectories between ages 9-17 and are subject to dissimilar demographic level variation. |
Absolute and relative energy costs of walking in a Brazilian adult probability sample
dos Anjos LA , da Mata Machado J , Wahrlich V , de Vasconcellos MT , Caspersen CJ . Med Sci Sports Exerc 2011 43 (11) 2211-8 BACKGROUND: Walking is commonly recommended for enhancing energy expenditure (EE), a basic principle in weight management, and cardiorespiratory fitness. However, walking EE varies with characteristics of a given population, especially by sex and age. PURPOSE: To measure EE of walking as influenced by physical and physiological characteristics of a sample of adults (≥ 20 years) living in Niteroi, Rio de Janeiro, Brazil. METHODS: Walking EE and heart rate were measured during a sub-maximal multi-stage treadmill test. The test stages lasted for 3 minutes each and started at a speed of 1.11 m/s and a grade of 0%. In the second stage, the grade was maintained at 0% but the speed was increased to 1.56 m/s and maintained at this speed but with grade raised by 2.5% at each stage until 10% at stage 6. The resting metabolic equivalent (METm) was measured via oxygen consumption prior to the test with the participants sitting quietly. RESULTS: METm (mean mL O2/kg/min +/- standard error) was lower both in women (2.85 +/- 0.03) and men (2.97 +/- 0.04) by almost 19% and 15%, respectively, compared with the conventionally-estimated MET (METe) of 3.5 mL O2/kg/min. Walking EE for any given speed and grade had an absolute intensity, expressed as multiples of METm or METe, that was practically equal between sexes and age groups, but, it incurred higher individual physiological demand, or relative intensity, for women and older adults. CONCLUSION: Resting EE reflected by using METe is overestimated in the adult population of Niteroi. Prescription of activities to counteract the existing wordwide obesity epidemic should be ideally based on individual physiological information, especially among women and older individuals. |
Adherence to the 2008 adult physical activity guidelines and mortality risk
Schoenborn CA , Stommel M . Am J Prev Med 2011 40 (5) 514-21 BACKGROUND: Mortality differentials by level and intensity of physical activity have been widely documented. A comprehensive review of scientific evidence of the health benefits of physical activity led the USDHHS to issue new Federal Guidelines for physical activity in 2008. Reductions in mortality risk associated with adherence to these Guidelines among the general U.S. adult population have not yet been studied. PURPOSE: This study compared the relative mortality risks of U.S. adults who met the 2008 Guidelines with adults who did not meet the recommendations. METHODS: Cox proportional hazards models were used to examine the relative mortality risks of U.S. adults aged ≥18 years, using data from the 1997-2004 National Health Interview Survey and linked mortality records for deaths occurring in 1997-2006 (analyzed in 2010). Risks for adults with and without chronic health conditions were examined separately. RESULTS: Meeting the recommendations for aerobic activity was associated with substantial survival benefits, especially among the population having chronic conditions, with estimated hazard ratios ranging from 0.65 to 0.75 (p<0.05). While strengthening activities by themselves did not appear to reduce mortality risks, they may provide added survival benefits to those already engaged in aerobic activities. The relative benefits of physical activity were greatest among adults who had at least one chronic condition. CONCLUSIONS: Adherence to the 2008 Physical Activity Guidelines was associated with reduced all-cause mortality risks among U.S. adults, after controlling for sociodemographic characteristics, BMI, smoking, and alcohol use. |
The relationship between mentally unhealthy days and depressive symptoms among older adults over time
Skarupski KA , Zack MM , Bienias JL , Scherr PA , Evans DA . J Appl Gerontol 2011 30 (2) 241-253 This article sought to determine the extent to which the number of self-reported mentally unhealthy days (MUDs) in the past 30 days estimates depressive symptoms in older adults. The sample of 4,321 community-dwelling residents aged 65 and above originated from an ongoing population-based study of older Blacks and Whites. Participants' data from 1993 through 2005 included the single MUD question and questions from the Center for Epidemiologic Studies Short Depression Scale (CES-D). Fourteen percent of participants had four or more depressive symptoms at baseline; of these, only 52% reported one or more MUD. Thirty-eight percent of those with one or more MUDs had four or more depressive symptoms. The results illustrate an interesting association regarding the measurements of two distinct, but related, mental health constructs. Although the number of MUDs was associated with having more depressive symptoms over time, the single-question MUD measure does not fully capture depressive symptomatology. |
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