RESUMO
Acrylonitrile (ACN), which is a widely used industrial chemical, induces cancers in multiple organs/tissues of rats by unresolved mechanisms. For this report, evidence for ACN-induced direct/indirect DNA damage and mutagenesis was investigated by assessing the ability of ACN, or its reactive metabolite, 2-cyanoethylene oxide (CEO), to bind to DNA in vitro, to form select DNA adducts [N7-(2'-oxoethyl)guanine, N2,3-ethenoguanine, 1,N6-ethenodeoxyadenosine, and 3,N4-ethenodeoxycytidine] in vitro and/or in vivo, and to perturb the frequency and spectra of mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene in rats exposed to ACN in drinking water. Adducts and frequencies and spectra of Hprt mutations were analyzed using published methods. Treatment of DNA from human TK6 lymphoblastoid cells with [2,3-14C]-CEO produced dose-dependent binding of 14C-CEO equivalents, and treatment of DNA from control rat brain/liver with CEO induced dose-related formation of N7-(2'-oxoethyl)guanine. No etheno-DNA adducts were detected in target tissues (brain and forestomach) or nontarget tissues (liver and spleen) in rats exposed to 0, 3, 10, 33, 100, or 300 ppm ACN for up to 105 days or to 0 or 500 ppm ACN for â¼15 months; whereas N7-(2'-oxoethyl)guanine was consistently measured at nonsignificant concentrations near the assay detection limit only in liver of animals exposed to 300 or 500 ppm ACN for ≥2 weeks. Significant dose-related increases in Hprt mutant frequencies occurred in T-lymphocytes from spleens of rats exposed to 33-500 ppm ACN for 4 weeks. Comparisons of "mutagenic potency estimates" for control rats versus rats exposed to 500 ppm ACN for 4 weeks to analogous data from rats/mice treated at a similar age with N-ethyl-N-nitrosourea or 1,3-butadiene suggest that ACN has relatively limited mutagenic effects in rats. Considerable overlap between the sites and types of mutations in ACN-exposed rats and butadiene-exposed rats/mice, but not controls, provides evidence that the carcinogenicity of these epoxide-forming chemicals involves corresponding mutagenic mechanisms.
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Acrilonitrila/toxicidade , Carcinógenos/toxicidade , Adutos de DNA/análise , Guanina/análise , Hipoxantina Fosforribosiltransferase/genética , Acrilonitrila/administração & dosagem , Acrilonitrila/metabolismo , Administração Oral , Animais , Carcinógenos/administração & dosagem , Carcinógenos/metabolismo , Células Cultivadas , Adutos de DNA/biossíntese , Relação Dose-Resposta a Droga , Óxido de Etileno/administração & dosagem , Óxido de Etileno/análogos & derivados , Óxido de Etileno/metabolismo , Óxido de Etileno/toxicidade , Feminino , Guanina/análogos & derivados , Guanina/biossíntese , Humanos , Hipoxantina Fosforribosiltransferase/metabolismo , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344RESUMO
Nationally, death rates from prescription opioid pain reliever (OPR) overdoses quadrupled during 1999-2010, whereas rates from heroin overdoses increased by <50%. Individual states and cities have reported substantial increases in deaths from heroin overdose since 2010. CDC analyzed recent mortality data from 28 states to determine the scope of the heroin overdose death increase and to determine whether increases were associated with changes in OPR overdose death rates since 2010. This report summarizes the results of that analysis, which found that, from 2010 to 2012, the death rate from heroin overdose for the 28 states increased from 1.0 to 2.1 per 100,000, whereas the death rate from OPR overdose declined from 6.0 per 100,000 in 2010 to 5.6 per 100,000 in 2012. Heroin overdose death rates increased significantly for both sexes, all age groups, all census regions, and all racial/ethnic groups other than American Indians/Alaska Natives. OPR overdose mortality declined significantly among males, persons aged <45 years, persons in the South, and non-Hispanic whites. Five states had increases in the OPR death rate, seven states had decreases, and 16 states had no change. Of the 18 states with statistically reliable heroin overdose death rates (i.e., rates based on at least 20 deaths), 15 states reported increases. Decreases in OPR death rates were not associated with increases in heroin death rates. The findings indicate a need for intensified prevention efforts aimed at reducing overdose deaths from all types of opioids while recognizing the demographic differences between the heroin and OPR-using populations. Efforts to prevent expansion of the number of OPR users who might use heroin when it is available should continue.
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Overdose de Drogas/mortalidade , Heroína/intoxicação , Adolescente , Adulto , Distribuição por Idade , Overdose de Drogas/etnologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Raciais/estatística & dados numéricos , Distribuição por Sexo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Although seatbelt use is known to reduce motor vehicle occupant crash injury and death, rear-seated adult occupants are less likely to use restraints. This study examines risk and protective factors associated with injury severity in front- and rear-seated adults involved in a motor vehicle crash in New York State. The Crash Outcome Data Evaluation System (CODES) (2016-2017) was used to examine injury severity in front- and rear-seated occupants aged 18 years or older (N = 958,704) involved in a motor vehicle crash. CODES uses probabilistic linkage of New York State hospitalization, emergency department, and police and motorist crash reports. Multivariable logistic regression models with MI analyze employed SAS 9.4. Odds ratios are reported as OR with 95% CI. The mortality rate was approximately 1.5 times higher for rear-seated than front-seated occupants (136.60 vs. 92.45 per 100,000), with rear-seated occupants more frequently unrestrained than front-seated occupants (15.28% vs. 1.70%, p < 0.0001). In adjusted analyses that did not include restraint status, serious injury/death was higher in rear-seated compared to front-seated occupants (OR:1.272, 1.146-1.412), but lower once restraint use was added (OR: 0.851, 0.771-0.939). Unrestrained rear-seated occupants exhibited higher serious injury/death than restrained front-seated occupants. Unrestrained teens aged 18-19 years old exhibit mortality per 100,000 occupants that is more similar to that of the oldest two age groups than to other young and middle-aged adults. Speeding, a drinking driver, and older vehicles were among the independent predictors of serious injury/death. Unrestrained rear-seated adult occupants exhibit higher severe injury/death than restrained front-seated occupants. When restrained, rear-seated occupants are less likely to be seriously injured than restrained front-seated occupants.
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Acidentes de Trânsito , Ferimentos e Lesões , Humanos , Acidentes de Trânsito/estatística & dados numéricos , Acidentes de Trânsito/mortalidade , Adulto , Pessoa de Meia-Idade , New York/epidemiologia , Feminino , Masculino , Adulto Jovem , Idoso , Adolescente , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/etiologia , Fatores de Risco , Fatores de Proteção , Idoso de 80 Anos ou mais , Cintos de Segurança/estatística & dados numéricosRESUMO
Introduction: COVID-19 was associated with increases in non-natural cause mortality in the U.S., including deaths due to drug overdose, homicide, and motor vehicle crashes. Initial reports indicated higher rates of non-natural mortality among ethnoracial minority groups. This report aims to clarify these disparities by documenting trends in non-natural mortality across ethnoracial groups during the 2020 COVID-19 surge in New York State. Methods: We report monthly trends in non-natural cause mortality (overall and stratified by ethnoracial status) in New York State from January 2019 through December 2020, which included the COVID-19 onset in March 2020. Results: Total mean monthly unintentional overdose rates per 100,000 increased from 17.45 (before surge: January 2019-February 2020) to 23.19 (after surge: March 2020-December 2020) (mean difference=5.73, 95% CI=3.82, 7.65; p<0.001). Mean monthly homicide death rates increased from 2.34 before surge to 3.55 after surge (mean difference=1.20, 95% CI=0.60, 1.81; p<0.001), with the increase seen primarily in the non-Latinx Black population. Although increasing unintentional overdose death rates before surge equally affected non-Latinx White, Latinx, and non-Latinx Black persons, they remained high for non-Latinx Black persons but dropped for the other 2 groups after the pandemic onset. None of the ethnoracial subgroups showed significant increases in suicide or motor vehicle crash death rates. Conclusions: Non-Latinx Black persons showed disproportionately high and sustained increased rates of unintentional overdose and homicide death rates after the 2020 COVID-19 surge in New York State. Fatality review and death scene investigation research is needed to better understand these disparities.
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There are reports that historically higher mortality observed for front- compared to rear-seated adult motor vehicle (MV) occupants has narrowed. Vast improvements have been made in strengthening laws and restraint use in front-, but not rear-seated occupants suggesting there may be value in expanding the science on rear-seat safety. METHODS: A linked 2016-2017 hospital and MV crash data set, the Crash Outcomes Data Evaluation System (CODES), was used to compare characteristics of front-seated (n = 115,939) and rear-seated (n = 5729) adults aged 18 years and older involved in a MV crash in New York State (NYS). A primary enforced seat belt law existed for front-seated, but not rear-seated occupants. Statistical analysis employed SAS 9.4. RESULTS: Compared to front-seated occupants, those rear-seated were more likely to be unrestrained (21.2% vs. 4.3%, p < 0.0001) and to have more moderate-to-severe injury/death (11.9% vs. 11.3%, p < 0.0001). Compared to restrained rear-seated occupants, unrestrained rear-seated occupants had higher moderate-to-severe injury/death (21.5% vs. 7.5%, p < 0.0001) and 4-fold higher hospitalization. More than 95% of ejections were unrestrained and had 7-fold higher medical charges. Unrestrained occupants' hospital stays were longer, charges and societal financial costs higher. CONCLUSIONS: These findings extend the science of rear-seat safety in seriously injured rear-seated occupants, document increased medical charges and support the need to educate consumers and policy makers on the health and financial risks of adults riding unrestrained in the rear seat. The lack of restraint use in adult rear-seated motor vehicle occupants consumes scarce health care dollars for treatment of this serious, but largely preventable injury.
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Preços Hospitalares , Ferimentos e Lesões , Adulto , Humanos , Acidentes de Trânsito , Veículos Automotores , Cintos de Segurança , HospitaisRESUMO
Rural areas of New York State (NYS) have higher rates of alcohol-related motor vehicle (MV) crash injury than metropolitan areas. While alcohol-related injury has declined across the three geographic regions of NYS, disparities persist with rural areas having smaller declines. Our study aim was to examine factors associated with alcohol-related MV crashes in Upstate and Long Island using multi-sourced county-level data that included the Crash Outcome Data Evaluation System (CODES) with emergency department visits and hospitalizations, traffic citations, demographic, economic, transportation, alcohol outlets, and Rural-Urban Continuum Codes (RUCCS). A cross-sectional study design employed zero-truncated negative binominal regression models to assess relative risks (RR) with 95% confidence interval (CI). Counties (n = 57, 56,000 alcohol-related crashes over the 3 year study timeframe) were categorized by mean annual alcohol-related MV injuries per 100,000 population: low (24.7 ± 3.9), medium (33.9 ± 1.7) and high (46.1 ± 8.0) (p < 0.0001). In multivariable analyses, alcohol-related MV injury was elevated for non-adjacent, non-metropolitan counties (RR 2.5, 95% CI: 1.6-3.9) with higher citations for impaired driving showing a small, but significant protective effect. Less metropolitan areas had higher alcohol-related MV injury with inconsistent alcohol-related enforcement measures. In summary, higher alcohol-related MV injury rates in non-metropolitan counties demonstrated a dose-response relationship with proximity to a metropolitan area. These findings suggest areas where intervention efforts might be targeted to lower alcohol-related MV injury.
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Acidentes de Trânsito/estatística & dados numéricos , Consumo de Bebidas Alcoólicas/epidemiologia , Intoxicação Alcoólica/epidemiologia , Aplicação da Lei , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Codificação Clínica , Estudos Transversais , Humanos , New York/epidemiologiaRESUMO
BACKGROUND: While increasing age is a known risk factor for neuroinvasive West Nile virus (WNV) disease, little is known about risk factors for West Nile fever (WNF). In 2003, United States blood centers identified WN (West Nile) viremic donors using nucleic acid-amplification tests (NATs), making it possible to prospectively determine risk factors for WNF. We report the characteristics of WN viremia among donors at Colorado's largest blood center and risk factors for WNF in viremic donors. METHODS: Prospective public health surveillance was conducted in WN viremic donors. NAT-reactive donors who developed WNV-specific IgM antibody were considered viremic donors. Demographic data were abstracted from blood center records for all viremic donors aged>or=18 years. Standardized telephone questionnaires were administered a median of 39 days following donation. Donors reporting fever and headache within seven days following donation were considered West Nile fever (WNF) cases. RESULTS: Of 66,771 donations screened from July 1-October 31, 146 (0.22%) were from viremic donors (1:457 donations). Of 135 surveyed donors, 81 (60%) were male. The median age was 49 years (range: 18-78). Forty-one (30%) donors developed WNF; of these, 12 (29%) visited a physician. Other reported symptoms included body aches (98%), eye pain (63%), and skin rash (61%). The risk of WNF was inversely correlated with age (odds ratio: 0.95 for every 1-year increase in age; 95% CI 0.91, 0.99; p=0.008). CONCLUSIONS: WN viremia was frequently identified in Colorado blood donors during the 2003 WNV epidemic. The high frequency of WNF and subsequent physician visits among healthy blood donors suggest substantial morbidity from WNF in the general population. The inverse correlation between age and WNF is a new finding and its pathophysiology is unknown.
Assuntos
Anticorpos Antivirais/sangue , Doadores de Sangue , Vigilância da População , Viremia/epidemiologia , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Colorado/epidemiologia , Feminino , Humanos , Imunoglobulina M/sangue , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Viremia/imunologia , Febre do Nilo Ocidental/sangue , Febre do Nilo Ocidental/imunologia , Febre do Nilo Ocidental/transmissão , Vírus do Nilo Ocidental/imunologiaRESUMO
Studies were performed to determine if the detoxification pathway of 1,3-butadiene (BD) through 3-butene-1,2-diol (BD-diol) is a major contributor to mutagenicity in BD-exposed mice and rats. First, female and male mice and rats (4-5 weeks old) were exposed by nose-only for 6h to 0, 62.5, 200, 625, or 1250 ppm BD or to 0, 6, 18, 24, or 36 ppm BD-diol primarily to establish BD and BD-diol exposure concentrations that yielded similar plasma levels of BD-diol, and then animals were exposed in inhalation chambers for 4 weeks to BD-diol to determine the mutagenic potency estimates for the same exposure levels and to compare these estimates to those reported for BD-exposed female mice and rats where comparable blood levels of BD-diol were achieved. Measurements of plasma levels of BD-diol (via GC/MS methodology) showed that (i) BD-diol accumulated in a sub-linear fashion during single 6-h exposures to >200 ppm BD; (ii) BD-diol accumulated in a linear fashion during single or repeated exposures to 6-18 ppm BD and then in a sub-linear fashion with increasing levels of BD-diol exposure; and (iii) exposures of mice and rats to 18 ppm BD-diol were equivalent to those produced by 200 ppm BD exposures (with exposures to 36 ppm BD-diol yielding plasma levels approximately 25% of those produced by 625 ppm BD exposures). Measurements of Hprt mutant frequencies (via the T cell cloning assay) showed that repeated exposures to 18 and 36 ppm BD-diol were significantly mutagenic in mice and rats. The resulting data indicated that BD-diol derived metabolites (especially, 1,2-dihydroxy-3,4-epoxybutane) have a narrow range of mutagenic effects confined to high-level BD (>or=200 ppm) exposures, and are responsible for nearly all of the mutagenic response in the rat and for a substantial portion of the mutagenic response in the mouse following high-level BD exposures.
Assuntos
Compostos de Epóxi/sangue , Compostos de Epóxi/urina , Glicóis/sangue , Glicóis/toxicidade , Glicóis/urina , Hipoxantina Fosforribosiltransferase/genética , Exposição por Inalação , Mutação/genética , Animais , Butadienos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Hemoglobinas/metabolismo , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344 , Reprodutibilidade dos Testes , Baço/citologia , Baço/efeitos dos fármacos , Baço/enzimologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/enzimologia , Fatores de TempoRESUMO
Experiments were performed: (i) to investigate potential age- and gender-dependent differences in mutagenic responses in T cells following exposures of B6C3F1 mice and F344 rats by inhalation for 2 weeks to 0 or 1250 ppm butadiene (BD), and (ii) to determine if exposures for 2 weeks to 62.5 ppm BD produce a mutagenic effect in female rats. To evaluate the effect of age on mutagenic response, mutant manifestation curves for splenic T cells of female mice exposed at 8-9 weeks of age were defined by measuring Hprt mutant frequencies (MFs) at multiple time points after BD exposure using a T cell cloning assay and comparing the resulting mutagenic potency estimate (calculated as the difference of areas under the mutant manifestation curves of treated versus control animals) to that reported for female mice exposed to BD in the same fashion beginning at 4-5 weeks of age. The shapes of the mutant T cell manifestation curves for spleens were different [e.g., the maximum BD-induced MFs in older mice (8.0+/-1.0 [S.D.]x10(-6)) and younger mice (17.8+/-6.1 x 10(-6)) were observed at 8 and 5 weeks post-exposure, respectively], but the mutagenic burden was the same for both age groups. To assess the effect of gender on mutagenic response, female and male rodents were exposed to BD at 4-5 weeks of age and Hprt MFs were measured when maximum MFs are expected to occur post-exposure. The resulting data demonstrated that the pattern for mutagenic susceptibility from high-level BD exposure is female mice>male mice>female rats>male rats. Exposures of female rats to 62.5 ppm BD caused a minor but significant mutagenic response compared with controls (n=16/group; P=0.03). These results help explain part of the differing outcomes/interpretations of data in earlier Hprt mutation studies in BD-exposed rodents.
Assuntos
Envelhecimento/genética , Butadienos/administração & dosagem , Butadienos/toxicidade , Exposição por Inalação , Mutagênese/efeitos dos fármacos , Caracteres Sexuais , Linfócitos T/efeitos dos fármacos , Animais , Células Clonais , Intervalos de Confiança , Feminino , Hipoxantina Fosforribosiltransferase/genética , Masculino , Camundongos , Testes de Mutagenicidade , Mutagênicos/administração & dosagem , Mutagênicos/toxicidade , Proteínas Mutantes/genética , Mutação/genética , Ratos , Ratos Endogâmicos F344 , Especificidade da Espécie , Baço/citologia , Baço/efeitos dos fármacos , Baço/enzimologia , Linfócitos T/enzimologia , Linfócitos T/metabolismoRESUMO
BACKGROUND: Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S. METHODS: We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet. Data were combined in the Crash Outcome Data Evaluation System's General Use Model and included motorcycle crash records probabilistically linked to emergency department and inpatient discharges for years 2005-2008. Medical outcomes were compared between partial and universal helmet law settings. We estimated adjusted relative risks (RR) and 95 % confidence intervals (CIs) for head, facial, traumatic brain, and moderate to severe head/facial injuries associated with helmet use within each helmet law setting using generalized log-binomial regression. RESULTS: Reported helmet use was higher in universal law states (88 % vs. 42 %). Median charges, adjusted for inflation and differences in state-incomes, were higher in partial law states (emergency department $1987 vs. $1443; inpatient $31,506 vs. $25,949). Injuries to the head and face, including traumatic brain injuries, were more common in partial law states. Effectiveness estimates of helmet use were higher in partial law states (adjusted-RR (CI) of head injury: 2.1 (1.9-2.2) partial law single vehicle; 1.4 (1.2, 1.6) universal law single vehicle; 1.8 (1.6-2.0) partial law multi-vehicle; 1.2 (1.1-1.4) universal law multi-vehicle). CONCLUSIONS: Medical charges and rates of head, facial, and brain injuries among motorcyclists were lower in universal law states. Helmets were effective in reducing injury in both helmet law settings; lower effectiveness estimates were observed in universal law states.
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OBJECTIVE: The goal was to examine the association between the New York State (NYS) upgraded child restraint law (UCRL) implemented in 2005 and the traffic injury rate among 4- to 6-year-old children in New York State. METHODS: A before/after comparison study of population-based, traffic injury rates for 4- to 6-year-old children, using 0- to 3-year-old children as a comparison group, was performed. The effects of UCRL on injury rates among 0- to 3-year-old and 4- to 6-year-old motor vehicle passengers were estimated by using monthly injury count data from the NYS Department of Motor Vehicles Accident Information System. RESULTS: Children 4 to 6 years of age experienced an 18% reduction in traffic injury rate (adjusted rate ratio [aRR]: 0.82 [95% confidence interval [CI]: 0.79-0.85]) after UCRL implementation, whereas the injury rate for children 0 to 3 years of age, who were not directly affected by the UCRL, did not change appreciably (aRR: 0.95 [95% CI: 0.90-0.99]). In Poisson regression analysis, the aRR for injury for 4- to 6-year-old children was 1.06 (95% CI: 0.92-1.22]) with adjustment for monthly child restraint use rates, which reveals that the significant reduction in the injury rate among 4- to 6-year-old children was mainly attributable to the 72% increase in the child restraint use rate after UCRL implementation (from 29% before UCRL implementation to 50% after implementation). CONCLUSIONS: This is the first study comparing traffic injury rates for booster seat-aged children before and after implementation of the booster seat law in a single state.
Assuntos
Acidentes de Trânsito/legislação & jurisprudência , Acidentes de Trânsito/estatística & dados numéricos , Sistemas de Proteção para Crianças/normas , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/prevenção & controle , Acidentes de Trânsito/prevenção & controle , Criança , Pré-Escolar , Humanos , Lactente , New YorkRESUMO
Comparisons of birth-weight-specific infant mortality indicate that low-birth-weight African American infants have lower mortality than low-birth-weight European American infants despite higher infant mortality overall-the "pediatric paradox." One explanation is heterogeneity in birth weight. Analyses of African American and European American births suggest that birth cohorts consist of two heterogeneous subpopulations. One appears to account for normal births, whereas the other may consist of compromised births. Estimates of infant mortality indicate that the compromised subpopulation has higher overall mortality but lower birth-weight-specific mortality. We attribute lower birth-weight-specific infant mortality in the compromised subpopulation to higher rates of fetal loss. Compared to European American birth cohorts, African American birth cohorts have (1) higher birth-weight-specific mortality in the normal subpopulation, (2) larger compromised subpopulations, and (3) lower birth-weight-specific mortality in the compromised subpopulation. Consequently, the pediatric paradox is attributable to greater rates of compromised pregnancies and higher fetal losses among African Americans.