Time spent traveling in motor vehicles and its association with overweight and abdominal obesity in Colombian adults who do not own a car
Florez Pregonero A , Gomez LF , Parra DC , Cohen DD , Arango Paternina CM , Lobelo F . Prev Med 2012 54 (6) 402-4 OBJECTIVE: This study examined associations between time spent traveling in motor vehicles per week (TSTMV) and BMI and abdominal obesity (AO) among Colombian adults residing in urban areas who do not own car. METHOD: Secondary data analysis of the 2005 National Nutrition Survey of Colombia was conducted. TSTMV was assessed using the long International Physical Activity Questionnaire. Body composition was measured in 7900 adults. Polytomous and binary logistic regressions were conducted, stratified by gender and adjusted for confounders, including physical activity (PA). RESULTS: Forty-two percent of participants were either overweight or obese according to their BMI, and 22.4% had AO. Males in the middle (10 to 149min) and highest (>150min) TSTMV tertiles were more likely to be overweight (POR=1.58, 95% CI=1.13-2.21 and POR=1.55, 95% CI=1.12-2.15 respectively, p-trend=0.012), obese (POR=2.39, 95% CI=1.43-3.99 and POR=1.93, 95% CI=1.22-3.08 respectively, p trend=0.019) and to have AO (POR=1.81, 95% CI=1.18-2.78 and POR=1.73, 95% CI=1.18-2.54 respectively, p-trend=0.009). Associations were not significant in females. CONCLUSIONS: TSTMV was positively associated with overweight and AO in adult Colombian males even after adjusting for PA. These findings highlight the potential deleterious health effects of sedentary behaviors such as prolonged traveling time, independently of having met PA recommendations. |
Improved survival among children with spina bifida in the United States
Shin M , Kucik JE , Siffel C , Lu C , Shaw GM , Canfield MA , Correa A . J Pediatr 2012 161 (6) 1132-7 OBJECTIVE: To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. STUDY DESIGN: A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. RESULTS: During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. CONCLUSIONS: The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival. |
Treatment duration for patients with drug-resistant tuberculosis, United States
Winston CA , Mitruka K . Emerg Infect Dis 2012 18 (7) 1201-2 TO THE EDITOR: In the United States, almost 80% of tuberculosis (TB) cases are diagnosed on the basis of positive culture results for Mycobacterium tuberculosis, and >90% of initial isolates are tested for drug susceptibilities. Recommended treatment durations are 6-9 months for patients with isoniazid- and rifampin-susceptible TB; <18 months for patients with rifampin-monoresistant TB; and, following culture conversion, 18-24 months for patients with isoniazid- and rifampin-resistant TB. Appropriately completed TB treatment maximizes patient and public health benefits and minimizes adverse events and costs. We examined treatment duration by drug resistance pattern among a national cohort of case-patients with TB diagnosed in the United States. |
Low pathogenic avian influenza A (H7N2) virus infection in immunocompromised adult, New York, USA, 2003
Ostrowsky B , Huang A , Terry W , Anton D , Brunagel B , Traynor L , Abid S , Johnson G , Kacica M , Katz J , Edwards L , Lindstrom S , Klimov A , Uyeki TM . Emerg Infect Dis 2012 18 (7) 1128-31 In 2003, infection with low pathogenic avian influenza A (H7N2) virus was identified in an immunocompromised man with fever and community-acquired pneumonia in New York, USA. The patient recovered. Although the source of the virus was not identified, this case indicates the usefulness of virus culture for detecting novel influenza A viruses. |
Assessment of the 2010 global measles mortality reduction goal: results from a model of surveillance data
Simons E , Ferrari M , Fricks J , Wannemuehler K , Anand A , Burton A , Strebel P . Lancet 2012 379 (9832) 2173-8 BACKGROUND: In 2008 all WHO member states endorsed a target of 90% reduction in measles mortality by 2010 over 2000 levels. We developed a model to estimate progress made towards this goal. METHODS: We constructed a state-space model with population and immunisation coverage estimates and reported surveillance data to estimate annual national measles cases, distributed across age classes. We estimated deaths by applying age-specific and country-specific case-fatality ratios to estimated cases in each age-country class. FINDINGS: Estimated global measles mortality decreased 74% from 535,300 deaths (95% CI 347,200-976,400) in 2000 to 139,300 (71,200-447,800) in 2010. Measles mortality was reduced by more than three-quarters in all WHO regions except the WHO southeast Asia region. India accounted for 47% of estimated measles mortality in 2010, and the WHO African region accounted for 36%. INTERPRETATION: Despite rapid progress in measles control from 2000 to 2007, delayed implementation of accelerated disease control in India and continued outbreaks in Africa stalled momentum towards the 2010 global measles mortality reduction goal. Intensified control measures and renewed political and financial commitment are needed to achieve mortality reduction targets and lay the foundation for future global eradication of measles. FUNDING: US Centers for Disease Control and Prevention (PMS 5U66/IP000161). |
Disseminated microsporidiosis in an immunosuppressed patient
Meissner EG , Bennett JE , Qvarnstrom Y , da Silva A , Chu EY , Tsokos M , Gea-Banacloche J . Emerg Infect Dis 2012 18 (7) 1155-8 We report a case of disseminated microsporidiosis in a patient with multiple myeloma who had received an allogeneic stem cell transplant requiring substantial immunosuppression. The causative organism was identified as Tubulinosema acridophagus, confirming this genus of microsporidia as a novel human pathogen. |
Molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in Arizona during 2001-2009
Kuzmin IV , Shi M , Orciari LA , Yager PA , Velasco-Villa A , Kuzmina NA , Streicker DG , Bergman DL , Rupprecht CE . PLoS Pathog 2012 8 (6) e1002786 In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001-2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T(242) in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other approaches. |
Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study
Dawood FS , Iuliano AD , Reed C , Meltzer MI , Shay DK , Cheng PY , Bandaranayake D , Breiman RF , Brooks WA , Buchy P , Feikin DR , Fowler KB , Gordon A , Hien NT , Horby P , Huang QS , Katz MA , Krishnan A , Lal R , Montgomery JM , Molbak K , Pebody R , Presanis AM , Razuri H , Steens A , Tinoco YO , Wallinga J , Yu H , Vong S , Bresee J , Widdowson MA . Lancet Infect Dis 2012 12 (9) 687-95 BACKGROUND: 18,500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. METHODS: We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. FINDINGS: We estimate that globally there were 201 200 respiratory deaths (range 105,700-395,600) with an additional 83,300 cardiovascular deaths (46,000-179,900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 59% occurred in southeast Asia and Africa. INTERPRETATION: Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. FUNDING: None. |
Reemergence and decline of dengue virus serotype 3 in Puerto Rico.
Santiago GA , McElroy-Horne K , Lennon NJ , Santiago LM , Birren BW , Henn MR , Munoz-Jordan JL . J Infect Dis 2012 206 (6) 893-901 BACKGROUND: The DENV-3 Indian subcontinent strain emerged in Puerto Rico in 1998 after a 21-year absence of this serotype. The rapid expansion of DENV-3 on the island correlated with the withdrawal of the other serotypes for 7 years. DENV-3 prevalence declined in 2008 and remains undetected. METHODS: We sequenced complete genomes of 92 DENV-3 clinical isolates to characterize the molecular evolution and phylogeography throughout 10 years of continued sampling (1998-2007). RESULTS: We document eight distinct lineages that emerged simultaneously and evolved independently. Two of the eight lineages were highly associated to transient introductions of foreign viruses, and two of the three endemic lineages covered the entire study period. We found evidence of temporal-geographical clustering only within the three endemic lineages. The phylogeography analysis combined with serotype-specific incidence data showed that transmission of a DENV serotype in a given location and time is usually correlated with the absence of the other serotype. CONCLUSIONS: Our study shows the co-transmission of DENV lineages through a complex dissemination pattern dissimilar to the evolutionary dynamics of the other serotypes in the island. High virus genetic diversity and a large naive population were underlying factors in the expansion of collapse of DENV-3 in Puerto Rico. |
International Health Regulations - what gets measured gets done
Ijaz K , Kasowski E , Arthur RR , Angulo FJ , Dowell SF . Emerg Infect Dis 2012 18 (7) 1054-7 The global spread of severe acute respiratory syndrome highlighted the need to detect and control disease outbreaks at their source, as envisioned by the 2005 revised International Health Regulations (IHR). June 2012 marked the initial deadline by which all 194 World Health Organization (WHO) member states agreed to have IHR core capacities fully implemented for limiting the spread of public health emergencies of international concern. Many countries fell short of these implementation goals and requested a 2-year extension. The degree to which achieving IHR compliance will result in global health security is not clear, but what is clear is that progress against the threat of epidemic disease requires a focused approach that can be monitored and measured efficiently. We developed concrete goals and metrics for 4 of the 8 core capacities with other US government partners in consultation with WHO and national collaborators worldwide. The intent is to offer an example of an approach to implementing and monitoring IHR for consideration or adaptation by countries that complements other frameworks and goals of IHR. Without concrete metrics, IHR may waste its considerable promise as an instrument for global health security against public health emergencies. |
Assessment of public health events through International Health Regulations, United States, 2007-2011
Kohl KS , Arthur RR , O'Connor R , Fernandez J . Emerg Infect Dis 2012 18 (7) 1047-53 Under the current International Health Regulations, 194 states parties are obligated to report potential public health emergencies of international concern to the World Health Organization (WHO) within 72 hours of becoming aware of an event. During July 2007-December 2011, WHO assessed and posted on a secure web portal 222 events from 105 states parties, including 24 events from the United States. Twelve US events involved human influenza caused by a new virus subtype, including the first report of influenza A(H1N1)pdm09 virus, which constitutes the only public health emergency of international concern determined by the WHO director-general to date. Additional US events involved 5 Salmonella spp. outbreaks, botulism, Escherichia coli O157:H7 infections, Guillain-Barre syndrome, contaminated heparin, Lassa fever, an oil spill, and typhoid fever. Rapid information exchange among WHO and member states facilitated by the International Health Regulations leads to better situation awareness of emerging threats and enables a more coordinated and transparent global response. |
Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch.
Kim YC , Song JM , Lipatov AS , Choi SO , Lee JW , Donis RO , Compans RW , Kang SM , Prausnitz MR . Eur J Pharm Biopharm 2012 81 (2) 239-47 Effective public health responses to an influenza pandemic require an effective vaccine that can be manufactured and administered to large populations in the shortest possible time. In this study, we evaluated a method for vaccination against avian influenza virus that uses a DNA vaccine for rapid manufacturing and delivered by a microneedle skin patch for simplified administration and increased immunogenicity. We prepared patches containing 700-mcm long microneedles coated with an avian H5 influenza hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The coating DNA dose increased with DNA concentration in the coating solution and the number of dip-coating cycles. Coated DNA was released into the skin tissue by dissolution within minutes. Vaccination of mice using microneedles induced higher levels of antibody responses and hemagglutination inhibition titers, and improved protection against lethal infection with avian influenza as compared to conventional intramuscular delivery of the same dose of the DNA vaccine. Additional analysis showed that the microneedle coating solution containing carboxymethylcellulose and a surfactant may have negatively affected the immunogenicity of the DNA vaccine. Overall, this study shows that DNA vaccine delivery by microneedles can be a promising approach for improved vaccination to mitigate an influenza pandemic. |
Risk of confirmed Guillain-Barre syndrome following receipt of monovalent inactivated influenza A (H1N1) and seasonal influenza vaccines in the Vaccine Safety Datalink Project, 2009-2010
Greene SK , Rett M , Weintraub ES , Li L , Yin R , Amato AA , Ho DT , Sheikh SI , Fireman BH , Daley MF , Belongia EA , Jacobsen SJ , Baxter R , Lieu TA , Kulldorff M , Vellozzi C , Lee GM . Am J Epidemiol 2012 175 (11) 1100-9 An increased risk of Guillain-Barre syndrome (GBS) following administration of the 1976 swine influenza vaccine led to a heightened focus on GBS when monovalent vaccines against a novel influenza A (H1N1) virus of swine origin were introduced in 2009. GBS cases following receipt of monovalent inactivated (MIV) and seasonal trivalent inactivated (TIV) influenza vaccines in the Vaccine Safety Datalink Project in 2009-2010 were identified in electronic data and confirmed by medical record review. Within 1-42 days following vaccination, 9 cases were confirmed in MIV recipients (1.48 million doses), and 8 cases were confirmed in TIV-only recipients who did not also receive MIV during 2009-2010 (1.72 million doses). Five cases following MIV and 1 case following TIV-only had an antecedent respiratory infection, a known GBS risk factor; furthermore, unlike TIV, MIV administration was concurrent with heightened influenza activity. In a self-controlled risk interval analysis comparing GBS onset within 1-42 days following MIV with GBS onset 43-127 days following MIV, the risk difference was 5.0 cases per million doses (95% confidence interval: 0.5, 9.5). No statistically significant increased GBS risk was found within 1-42 days following TIV-only vaccination versus 43-84 days following vaccination (risk difference = 1.1 cases per million doses, 95% confidence interval: -3.1, 5.4). Further evaluation to assess GBS risk following both vaccination and respiratory infection is warranted. |
Provider perceptions of barriers and facilitators of HPV vaccination in a high-risk community
Javanbakht M , Stahlman S , Walker S , Gottlieb S , Markowitz L , Liddon N , Plant A , Guerry S . Vaccine 2012 30 (30) 4511-6 BACKGROUND: Maximizing HPV vaccine uptake among those at highest risk for cervical cancer is critical. We explored healthcare provider perspectives on factors influencing HPV vaccination among adolescent girls in a community with high cervical cancer rates. METHODS: From March to May 2009, we conducted in-depth interviews with 21 medical staff providing care to adolescent girls at two clinics in Los Angeles, CA, serving a predominantly Hispanic population with high cervical cancer rates. Interviews were recorded and transcribed data were reviewed for coding and thematic content related to potential barriers and facilitators of HPV vaccination. RESULTS: Providers and medical staff overwhelmingly focused on parental beliefs as barriers to HPV vaccination. Perceived parental misconceptions acting as barriers included the belief that adolescents do not need vaccinations and that no-cost vaccine programs like Vaccines for Children are only available for younger children. Perceived parental concerns that the vaccine will promote sexual activity were prevalent, which prompted providers to frame HPV vaccine as a "routine" vaccine. However, the medical staff felt mothers with a friend or relative supportive of HPV vaccination were more likely to request the vaccine. The staff also noted that for Hispanic parents the "preferred" source of information is peers; if the "right people" in the community were supportive of HPV vaccine, parents were more willing to vaccinate. Other barriers included lack of immunization records among immigrant parents and a difficult-to-reach, mobile clientele. CONCLUSIONS: Providers noted a number of barriers to HPV vaccination, including some perceived parental misconceptions that could be addressed with education about the need for adolescent vaccines and available free vaccine programs. Because community support appears particularly important to Hispanic parents, the use of promotoras - peer liaisons between health organizations and the community - may increase HPV vaccine uptake in this population. |
Guillain-Barre syndrome during the 2009-2010 H1N1 influenza vaccination campaign: population-based surveillance among 45 million Americans
Wise ME , Viray M , Sejvar JJ , Lewis P , Baughman AL , Connor W , Danila R , Giambrone GP , Hale C , Hogan BC , Meek JI , Murphree R , Oh JY , Reingold A , Tellman N , Conner SM , Singleton JA , Lu PJ , Destefano F , Fridkin SK , Vellozzi C , Morgan OW . Am J Epidemiol 2012 175 (11) 1110-9 Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barre syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009-May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments. |
Adverse event reports after tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines in pregnant women
Zheteyeva YA , Moro PL , Tepper NK , Rasmussen SA , Barash FE , Revzina NV , Kissin D , Lewis PW , Yue X , Haber P , Tokars JI , Vellozzi C , Broder KR . Am J Obstet Gynecol 2012 207 (1) 59 e1-7 OBJECTIVE: We sought to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women who received tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). STUDY DESIGN: We searched VAERS for reports of pregnant women who received Tdap from Jan. 1, 2005, through June 30, 2010. We conducted a clinical review of reports and available medical records. RESULTS: We identified 132 reports of Tdap administered to pregnant women; 55 (42%) described no adverse event (AE). No maternal or infant deaths were reported. The most frequent pregnancy-specific AE was spontaneous abortion in 22 (16.7%) reports. Injection site reactions were the most frequent non-pregnancy-specific AE found in 6 (4.5%) reports. One report with a major congenital anomaly (gastroschisis) was identified. CONCLUSION: During a time when Tdap was not routinely recommended in pregnancy, review of reports to VAERS in pregnant women after Tdap did not identify any concerning patterns in maternal, infant, or fetal outcomes. |
Reduced inflammation and CD4 loss in acute SHIV infection during oral PrEP
Kersh EN , Luo W , Zheng Q , Adams DR , Hanson D , Youngpairoj AS , Cong ME , Butler K , Hendry RM , McNicholl JM , Heneine W , Garcia-Lerma JG . J Infect Dis 2012 206 (5) 770-9 BACKGROUND: The impact of Pre-exposure Prophylaxis (PrEP) with anti-retrovirals on breakthrough HIV or SHIV infection is not fully documented. We addressed the hypothesis that SHIV(SF162P3) infection despite active PrEP results in altered early immune parameters compared to untreated infection. METHODS: Eleven rhesus macaques were infected during repeated, rectal, low-dose SHIV(SF162P3) exposures while receiving concurrent, oral PrEP (Truvada, n=2, or GS7340, n=4), or as untreated controls (n=5). We measured SHIV RNA, inflammatory cytokines, CD4 cells, and SHIV-specific and memory T cells until 20 weeks post peak viremia. RESULTS: SHIV infection during PrEP resulted in 100-fold lower peak viremia and lower IL-15, IL-18, and IL-1Ra levels compared to controls (p<0.05; Wilcoxon rank-sum test). Unlike controls, PrEP-treated macaques showed no significant CD4 reduction during acute infection, and developed more SHIV-specific central memory T cells relative to controls. Following in-vivo CD8(+) cell depletion, viremia rose to similar levels, indicating that CD8(+) cells were critical for viral control in both groups. CONCLUSIONS: PrEP with anti-retrovirals has beneficial effects on early SHIV infection even when infection is not prevented. While long-term immune control could not be examined in this SHIV infection model, our results suggest that PrEP results in improved early disease parameters in breakthrough infections. |
Subtyping botulinum neurotoxins by sequential multiple endoproteases in-gel digestion coupled with mass spectrometry
Wang D , Baudys J , Rees J , Marshall KM , Kalb SR , Parks BA , Nowaczyk L , Pirkle JL , Barr JR . Anal Chem 2012 84 (11) 4652-4658 Botulinum neurotoxin (BoNT) is one of the most toxic substances known. BoNT is classified into seven distinct serotypes labeled A-G. Among individual serotypes, researchers have identified subtypes based on amino acid variability within a serotype and toxin variants with minor amino acid sequence differences within a subtype. BoNT subtype identification is valuable for tracing and tracking bacterial pathogens. A proteomics approach is useful for BoNT subtyping since botulism is caused by botulinum neurotoxin and does not require the presence of the bacteria or its DNA. Enzymatic digestion and peptide identification using tandem mass spectrometry determines toxin protein sequences. However, with the conventional one-step digestion method, producing sufficient numbers of detectable peptides to cover the entire protein sequence is difficult, and incomplete sequence coverage results in uncertainty in distinguishing BoNT subtypes and toxin variants because of high sequence similarity. We report here a method of multiple enzymes and sequential in-gel digestion (MESID) to characterize the BoNT protein sequence. Complementary peptide detection from toxin digestions has yielded near-complete sequence coverage for all seven BoNT serotypes. Application of the method to a BoNT-contaminated carrot juice sample resulted in the identification of 98.4% protein sequence which led to a confident determination of the toxin subtype. (This article not subject to U.S. Copyright. Published 2012 by the American Chemical Society.) |
Two-dimensional high performance liquid chromatography separation and tandem mass spectrometry detection of atrazine and its metabolic and hydrolysis products in urine
Kuklenyik Z , Panuwet P , Jayatilaka NK , Pirkle JL , Calafat AM . J Chromatogr B Analyt Technol Biomed Life Sci 2012 901 1-8 Atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine] is the most widely used herbicide in the United States. In recent years, there has been controversy about atrazine's potential endocrine/reproductive and neurological adverse effects in wildlife and humans. The controversy triggered several environmental and epidemiologic studies, and it generated needs for sensitive and selective analytical methods for the quantification of atrazine, atrazine metabolites, and degradation or hydrolysis products. We developed a two-dimensional high performance liquid chromatography (2D-HPLC) method with isotope dilution tandem mass spectrometry detection to measure atrazine in urine, along with 11 atrazine metabolites and hydrolysis products, including 6-chloro (Cl), 6-mercapto (Mer) and 6-hydroxy (OH) derivatives, and their desethyl, desisopropyl and diamino atrazine analogs (DEA, DIA and DAA, respectively). The 2D-HPLC system incorporated strong cation exchange and reversed phase separation modes. This versatile approach can be used for the quantitative determination of all 12 compounds in experimental animals for toxicological studies. The method requires only 10mcL of urine, and the limits of detection (LODs) range from 10 to 50mcg/L. The method can also be applied to assess atrazine exposure in occupational settings by measurement of 6-Cl and 6-Mer analogs, which requires only 100mcL of urine with LODs of 1-5mcg/L. Finally, in combination with automated off-line solid phase extraction before 2D-HPLC, the method can also be applied in non-occupational environmental exposure studies for the determination of -6-Cl and 6-Mer metabolites, using 500mcL of urine and LODs of 0.1-0.5mcg/L. |
Using a physiologically based pharmacokinetic model to link urinary biomarker concentrations to dietary exposure of perchlorate
Yang Y , Tan YM , Blount B , Murray C , Egan S , Bolger M , Clewell H . Chemosphere 2012 88 (8) 1019-27 Exposure to perchlorate is widespread in the United States and many studies have attempted to character the perchlorate exposure by estimating the average daily intakes of perchlorate. These approaches provided population-based estimates, but did not provide individual-level exposure estimates. Until recently, exposure activity database such as CSFII, TDS and NHANES become available and provide opportunities to evaluate the individual-level exposure to chemical using exposure surveillance dataset. In this study, we use perchlorate as an example to investigate the usefulness of urinary biomarker data for predicting exposures at the individual level. Specifically, two analyses were conducted: (1) using data from a controlled human study to examine the ability of a physiologically based pharmacokinetic (PBPK) model to predict perchlorate concentrations in single-spot and cumulative urine samples; and (2) using biomarker data from a population-based study and a PBPK model to demonstrate the challenges in linking urinary biomarker concentrations to intake doses for individuals. Results showed that the modeling approach was able to characterize the distribution of biomarker concentrations at the population level, but predicting the exposure-biomarker relationship for individuals was much more difficult. The type of information needed to reduce the uncertainty in estimating intake doses, for individuals, based on biomarker measurements is discussed. |
Measurement of elemental concentration of aerosols using spark emission spectroscopy
Diwakar PK , Kulkarni P . J Anal At Spectrom 2012 27 (7) 1101-1109 A coaxial microelectrode system has been used to collect and analyse the elemental composition of aerosol particles in near real-time using spark emission spectroscopy. The technique involves focused electrostatic deposition of charged aerosol particles onto the flat tip of a microelectrode, followed by introduction of spark discharge. A pulsed spark discharge was generated across the electrodes with input energy ranging from 50 to 300 mJ per pulse, resulting in the formation of controlled pulsed plasma. The particulate matter on the cathode tip is ablated and atomized by the spark plasma, resulting in atomic emissions which are subsequently recorded using a broadband optical spectrometer for element identification and quantification. The plasma characteristics were found to be very consistent and reproducible even after several thousands of spark discharges using the same electrode system. The spark plasma was characterized by measuring the excitation temperature (~7000 to 10,000 K), electron density (~10(16)cm-3), and evolution of spectral responses as a function of time. The system was calibrated using particles containing Pb, Si, Na and Cr. Absolute mass detection limits in the range 11 pg to 1.75 ng were obtained. Repeatability of spectral measurements varied from 2 to 15%. The technique offers key advantages over similar microplasma-based techniques such as laser-induced breakdown spectroscopy, as: (i) it does not require any laser beam optics and eliminates any need for beam alignment, (ii) pulse energy from dc power supply in SIBS system can be much higher compared to that from laser source of the same physical size, and (iii) it is quite conducive to compact, field-portable instrumentation. |
Endogenous galectin-3 controls experimental malaria in a species-specific manner
Toscano MA , Tongren JE , De Souza JB , Liu FT , Riley EM , Rabinovich GA . Parasite Immunol 2012 34 (7) 383-387 Galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses. Galectin-3 has been implicated in several immunological processes as well as in pathogen recognition through specific binding to glycosylated receptors on the surface of host cells or microorganisms. In spite of considerable evidence supporting a role for galectin-3 in host-pathogen interactions, the relevance of this lectin in the regulation of the host defence mechanisms in vivo is poorly understood. In this study, we analysed the impact of galectin-3 deficiency during infection with three distinct species of rodent malaria parasites, Plasmodium yoelii 17XNL, Plasmodium berghei ANKA and Plasmodium chabaudi AS. We found that galectin-3 deficiency showed a marginal effect on the course of parasitaemia during P. chabaudi infection, but did not alter the course of parasitaemia during P. berghei infection. However, lack of galectin-3 significantly reduced P. yoelii parasitaemia. This reduced parasitaemia in Lgals3(-/-) mice was consistent with higher titres of anti-P. yoelii MSP1(19) IgG2b isotype antibodies when compared with their wild-type counterparts. Our results reflect the complexity and singularity of host-pathogen interactions, indicating a species-specific role of endogenous galectin-3 in the control of parasite infections and the modulation of antibody responses. |
Assessment of pulmonary fibrogenic potential of multiwalled carbon nanotubes in human lung cells
Mishra A , Rojanasakul Y , Chen BT , Castranova V , Mercer RR , Wang LY . J Nanomater 2012 2012 1-11 Multiwalled carbon nanotubes have been shown to possess unusual fibrogenic activity in vivo and are currently the focus of intense toxicological investigations. This study further determines the fibrogenic potential of well-dispersed MWCNT in human lung cell culture models and to develop a novel platform for understanding the cellular mechanisms of MWCNT-induced lung fibrosis. Survanta, a natural lung surfactant, showed effectiveness in dispersing agglomerates of MWCNT to fine structures similar in size to aerosolized one. At relevant low doses (0.002-0.2 mcg/cm(2)), MWCNT exhibited a dose-dependent bio-effect on the human lung epithelial cells which is more pronounced in dispersed-MWCNT compared to non-dispersed form. Significantly elevated levels of fibrogenic mediators, such as transforming growth factor-beta 1 and matrix metalloprotienases-9 were observed in the dispersed-MWCNT treated lung epithelial cells. Based on previous in vivo studies showing that dispersed-MWCNT penetrated the interstitium and caused rapid interstitial fibrosis, we evaluated the potential direct interaction between lung fibroblasts and MWCNT. Direct stimulation of human lung fibroblast cell proliferation, collagen expression and fibroblast growth factor-2 were observed which suggests novel mechanisms of MWCNT-induced lung fibrosis. Our results indicate that the dispersion status of MWCNT determines their fibrogenic activity which is consistent with in vivo findings. |
Comparison between free serum thyroxine levels, measured by analog and dialysis methods, in the presence of perfluorooctane sulfonate and perfluorooctanoate
Lopez-Espinosa MJ , Fitz-Simon N , Bloom MS , Calafat AM , Fletcher T . Reprod Toxicol 2012 33 (4) 552-5 Results from animal studies have shown that negative associations between serum levels of free thyroxine (FT4) and perfluorooctane sulfonate (PFOS) at concentrations much higher than those reported for any exposed population may be due to bias in analog methods used for measuring FT4. We aimed to assess if there is evidence of differences between human FT4 measurements in serum by an analog and a dialysis method due to the presence of PFOS or perfluorooctanoate (PFOA) in a population of 50 adults with typical US serum PFOS concentrations but higher PFOA concentrations. Mean analog-dialysis difference was -0.02 (95% CI=-0.06, 0.02). Regressing the difference between FT4 measurements on either PFOA or PFOS serum concentrations yielded slopes close to zero. The present findings do not indicate any observable bias from the use of the analog with respect to the dialysis method, across the range of PFOS and PFOA concentrations in this population. |
Comparison of nasopharyngeal flocked swabs and nasopharyngeal wash collection methods for respiratory virus detection in hospitalized children using real-time polymerase chain reaction
DeByle C , Bulkow L , Miernyk K , Chikoyak L , Hummel KB , Hennessy T , Singleton R . J Virol Methods 2012 185 (1) 89-93 This paper describes the molecular detection of respiratory viruses from nasopharyngeal flocked swabs (flocked swabs) and nasopharyngeal washes (washes) in a clinical setting. Washes and flocked swabs collected from children <3 years old hospitalized with a lower respiratory tract infection were tested for parainfluenza virus 1-3, respiratory syncytial virus, influenza A and B and metapneumovirus (Group 1) and adenovirus, rhinovirus and coronavirus (Group 2) using real-time reverse transcriptase PCR (rRT-PCR). A consensuses standard was used to determine sensitivity and compare cycle thresholds (C(T)) of washes and flocked swabs for each virus and group of viruses. Sensitivities ranged from 79-89% and 69-94% for flocked swabs and washes, respectively, excluding AdV which had a sensitivity of 35% for flocked swabs. When the flocked swabs and washes of Group 1 viruses were collected on the day of admission, the sensitivity of both sample types was 100%. Wash specimens had a lower C(T) value and higher sensitivity than flocked swabs; however there was no statistical difference in the sensitivity of a flocked swab (89%) versus wash (93%) for the detection of Group 1 viruses, particularly when samples were collected on the same day. Flocked swabs may be a useful alternative to washes for detection of respiratory viruses in clinical settings. |
Maternal mid-upper arm circumference is associated with birth weight among HIV-infected Malawians
Ramlal RT , Tembo M , Soko A , Chigwenembe M , Ellington S , Kayira D , King CC , Chasela C , Jamieson D , van der Horst C , Bentley ME , Adair LS . Nutr Clin Pract 2012 27 (3) 416-421 The authors examined the relationship of maternal anthropometry to fetal growth and birth weight among 1005 human immunodeficiency virus (HIV)-infected women in Lilongwe, Malawi, who consented to enrollment in the Breastfeeding, Antiretrovirals, and Nutrition Study (www.thebanstudy.org). Anthropometric assessments of mid-upper arm circumference (MUAC), arm muscle area (AMA), and arm fat area (AFA) were collected at the baseline visit between 12 and 30 weeks' gestation and in up to 4 follow-up prenatal visits. In longitudinal analysis, fundal height increased monotonically at an estimated rate of 0.92 cm/wk and was positively and negatively associated with AMA and AFA, respectively. These latter relationships varied over weeks of follow-up. Baseline MUAC, AMA, and AFA were positively associated with birth weight (MUAC: 31.84 g/cm(2), 95% confidence interval [CI], 22.18-41.49 [P < .01]; AMA: 6.88 g/cm(2), 95% CI, 2.51-11.26 [P < .01]; AFA: 6.97 g/cm(2), 95% CI, 3.53-10.41 [P < .01]). In addition, MUAC and AMA were both associated with decreased odds for low birth weight (LBW; <2500 g) (MUAC: odds ratio [OR] = 0.85, 95% CI, 0.77-0.94 [P < .01]; AMA: OR = 0.95, 95% CI, 0.91-0.99 [P < .05]). These findings support the use of MUAC as an efficient, cost-effective screening tool for LBW in HIV-infected women, as in HIV-uninfected women. |
Analysis of heart rate variability for predicting cardiorespiratory events in infants
Lewicke A , Corwin M , Schuckers M , Xu XY , Neuman M , Schuckers S , CHIME Study Group . Biomed Signal Process Control 2012 7 (4) 325-332 Cardiorespiratory events (CREs), including bradycardia and apnea, in infants are a major concern for physicians and families. Our hypothesis was that there is a difference in the heart rate variability (HRV) of infants who have CREs when compared to normal control infants. The purpose of this study was to develop CRE prediction models based on HRV measured during a polysomnographic (PSG) recording. ANCOVA analysis accounting for factors such as age and sleep state show a relationship between HRV variables and CRE. Prediction models, including neural networks and support vector machines, were developed to predict CRE within either (a) 1-week or (b) 1-month after the PSG. The support vector machine prediction accuracy, for CRE susceptibility one month after the PSG on an independent testing dataset, was 50.0% sensitivity and 82.6% specificity. Although the developed prediction models were not sufficiently accurate for clinical decision making, these results support the potential role of abnormalities in autonomic control of heart rate among infants at risk for CREs. (C) 2011 Elsevier Ltd. All rights reserved. |
Do US medical students report more training on evidence-based prevention topics?
Frank E , Schlair S , Elon L , Saraiya M . Health Educ Res 2012 28 (2) 265-75 Little is known about the extent to which evidence-based prevention topics are taught in medical school. All class of 2003 medical students (n=2316) at 16 US schools were eligible to complete three questionnaires: at the beginning of first and third years and in their senior year, with 80.3% responding. We queried these students about 21 preventive medicine topics, concerning the extent of their training and their patient counseling frequency at some of these time points. At the beginning of the third year, self-reported extensive training was low for all preventive medicine topics (range 7-26%). USPSTF-recommended topics received more curricular time (median for topics: 36% if recommended versus 24.5% if not, P=0.025), as did topics addressed through testing rather than through discussion (median for topics: 37% for testing and 25% for discussion, P=0.005). Extensive training was always associated with higher counseling frequency, and intention to go into primary care, female gender, a positive attitude toward prevention and positive personal health habits were associated with higher counseling frequency. Although some bemoan the overall low levels of US medical students' prevention-related training and practice, we demonstrate that at least they are preferentially evidence-based, a novel and encouraging finding for preventionists. |
Paid sick leave and nonfatal occupational injuries
Asfaw A , Pana-Cryan R , Rosa R . Am J Public Health 2012 102 (9) e59-64 OBJECTIVES: We examined the association between US workers' access to paid sick leave and the incidence of nonfatal occupational injuries from the employer's perspective. We also examined this association in different industries and occupations. METHODS: We developed a theoretical framework to examine the business value of offering paid sick leave. Data from the National Health Interview Survey were used to test the hypothesis that offering paid sick leave is associated with a reduced incidence of occupational injuries. We used data on approximately 38,000 working adults to estimate a multivariate model. RESULTS: With all other variables held constant, workers with access to paid sick leave were 28% (95% confidence interval = 0.52, 0.99) less likely than workers without access to paid sick leave to be injured. The association between the availability of paid sick leave and the incidence of occupational injuries varied across sectors and occupations, with the greatest differences occurring in high-risk sectors and occupations. CONCLUSIONS: Our findings suggest that, similar to other investments in worker safety and health, introducing or expanding paid sick leave programs might help businesses reduce the incidence of nonfatal occupational injuries, particularly in high-risk sectors and occupations. (Am J Public Health. Published online ahead of print July 19, 2012: e1-e6. doi:10.2105/AJPH.2011.300482). |
Promoting and protecting worker health and safety in the republic of Korea agricultural sector
Calvert GM , Lee K , Roh S , Davis KG , Tak S . J Agromedicine 2012 17 (3) 326-37 With the exception of agriculture, all other Republic of Korea industrial sectors have comprehensive systems in place for workplace surveillance (i.e., disease, injury, and exposure), research, and targeted interventions. However, because few statistics are available on the occupational health and safety conditions in the Republic of Korea agricultural sector, there is little information to guide interventions to prevent hazardous agricultural exposures. The scant information that is currently available suggests that agriculture ranks among the most hazardous industries in the Republic of Korea. Building on information obtained at the International Symposium on Development of Prevention Strategies for Agricultural Health and Safety held in Suwon, Republic of Korea, in 2005, and embellished with examples of surveillance, research, and intervention activities conducted in the United States and elsewhere, this article provides guidance to promote and protect the health of Korean agricultural workers. This information can also guide other countries to reduce agricultural hazards. |
Immunotoxicology of arc welding fume: worker and experimental animal studies
Zeidler-Erdely PC , Erdely A , Antonini JM . J Immunotoxicol 2012 9 (4) 411-25 Arc welding processes generate complex aerosols composed of potentially hazardous metal fumes and gases. Millions of workers worldwide are exposed to welding aerosols daily. A health effect of welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of welding fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of welding fume pulmonary exposure on local and systemic immune responses. |
Improving dental care: the intersection of private and public health practice
Bailey W . J Evid Based Dent Pract 2012 12 (2) 50-2 Readers may wonder why the US Cetners for Disease Control and Prevention (CDC) is providing commentary on evidence-based dental practices in clinical settings. Some believe that CDC is focused on population health with little attention given to dental services delivered to patients in clinical practice; however, this is not the reality. CDC is concerned with both clinical and community-based interventions to promote health and prevent disease and is increasingly interested in the linkages between the two. |
Prostate-specific antigen as a biomarker of condom failure: comparison of three laboratory assays and self-reported condom use problems in a randomized trial of female condom performance
Walsh T , Warner L , Macaluso M , Frezieres R , Snead M , Wraxall B . Contraception 2012 86 (1) 55-61 BACKGROUND: Prostate-specific antigen (PSA), a biomarker for semen exposure, may provide a more objective measure of condom failure than subject self-reports. Methods for measuring PSA vary and their comparability with respect to assessing condom performance has not been adequately evaluated. This study compared results from three different PSA assays of vaginal samples collected by subjects in a randomized clinical trial which compared the performance of female condoms. STUDY DESIGN: We selected 30 pairs of pre- and post-coital vaginal samples from subjects who reported condom functionality problems or whose original PSA assay was positive. Samples were retested using three different PSA assays [quantitative enzyme-linked immunoassay (EIA), rocket immune-electrophoresis (RIE) and chromatographic immunoassay (CIA)]. We compared the proportion of condom uses where the post-coital PSA result indicated semen exposure for each of the three assays. RESULTS: Despite varying levels of sensitivity, the results from all three assays were remarkably consistent. Self-reported condom failures did not correlate well with positive PSA results, suggesting that exclusive reliance on either PSA or user self-report may be inadequate for assessing condom functionality. CONCLUSION: In combination with user self-report of condom failure, PSA testing provides a reliable, objective marker of condom functionality. Studies based on PSA testing may improve on conventional contraceptive clinical trials by offering a more direct assessment of a condom product's ability to prevent semen exposure. |
Emergency Contraception and Risk for Sexually Transmitted Infections Among U.S. Women
Habel MA , Leichliter JS . J Womens Health (Larchmt) 2012 21 (9) 910-6 BACKGROUND: Since Food and Drug Administration (FDA) licensure of emergency contraception (EC) over-the-counter (OTC) in 2006, this is the first U.S. study to use a nationally representative sample of reproductive-aged women (15-44) to explore the relationship between receipt and use of EC and sexually transmitted infection (STI)-related health services. METHODS: Using a sample of 6329 women from the National Survey of Family Growth 2006-2008, we examined the relationship between lifetime EC use and recent receipt of EC and demographics, sexual behaviors, and STI-related services. Variables significant at p<0.10 in bivariate analyses were examined using multivariable logistic regression models. RESULTS: Overall, 10% (704) of the sample had ever used EC. Most EC users had received EC from a family planning clinic (51%), drugstore (23%), or doctor's office (17%). In adjusted analyses, demographic factors associated with receipt of EC in the past 12 months included never married (adjusted odds ratio [AOR] 4.0) and living in a metropolitan statistical area (AOR 4.2). Women reporting multiple partners (2+) (AOR 2.4), inconsistent condom use (AOR 3.4), and having recently been tested for chlamydia (AOR 2.0) had higher odds of receiving EC in the past 12 months. Findings among women ever reporting EC use were similar, except women who had 4+ lifetime partners (AOR 2.5) and had recently received a chlamydia diagnosis (AOR 2.2) had higher odds of ever having used EC. CONCLUSIONS: EC recipients were no more likely than nonrecipients to have received STI counseling or screening despite greater numbers of sex partners in the past year. This research indicates that women are accessing EC in pharmacies, which may be a missed opportunity for counseling and testing. |
A community-based randomized trial of a faith-placed intervention to reduce cervical cancer burden in Appalachia
Studts CR , Tarasenko YN , Schoenberg NE , Shelton BJ , Hatcher-Keller J , Dignan MB . Prev Med 2012 54 (6) 408-14 OBJECTIVE: Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3years). METHOD: This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005-June 2008). Women aged 40-64 and overdue for screening were recruited from churches and individually randomized to treatment (n=176) or wait-list control (n=169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome. RESULTS: Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR=2.56, 95% CI: 1.03-6.38, p=0.04. Independent of group, recently screened participants (last Pap >1 but <5years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap ≥5years ago), OR=2.50, 95% CI: 1.48-4.25, p=0.001. CONCLUSIONS: The intervention was associated with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women. |
Frequency of prescription pain reliever nonmedical use: 2002-2003 and 2009-2010
Jones CM . Arch Intern Med 2012 172 (16) 1-2 The public health consequences associated with the nonmedical use of prescription pain relievers such as oxycodone, hydrocodone, and methadone have dramatically increased over the last decade.1 In 2009, 15 597 people died of overdoses involving these drugs—a 109% increase since 2002.2 Prior studies examining prescription pain reliever overdose deaths found that nonmedical use was common among decedents before death.3,4 National estimates of past-year nonmedical use of these drugs, however, have remained stable since 2002.5,6 These estimates include the spectrum of nonmedical users from those who used pain relievers once or twice to those who were more frequent or chronic nonmedical users. This Research Letter attempts to determine if the subset of chronic nonmedical users of pain relievers—those using 200 days or more in the past year—has increased since 2002, in parallel with fatal overdoses of these drugs. Understanding trends in the frequency of nonmedical use can help identify populations at greatest risk for overdoses. |
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