RESUMO
Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management.
Assuntos
Síndrome de Beckwith-Wiedemann , Hepatoblastoma , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias Embrionárias de Células Germinativas , Tumor de Wilms , Humanos , Síndrome de Beckwith-Wiedemann/complicações , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Hepatoblastoma/etiologia , Hepatoblastoma/genética , Impressão Genômica , Tumor de Wilms/diagnóstico , Tumor de Wilms/genética , Fenótipo , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Neoplasias Renais/genética , Neoplasias Embrionárias de Células Germinativas/genética , Metilação de DNARESUMO
OBJECTIVE: Alcohol-impaired driving results in thousands of deaths annually. Alcohol ignition interlocks require a negative breath test to start a vehicle's engine, and 44 states have mandated some form of interlock law for drivers convicted of driving while intoxicated (DWI). The objective of this study was to estimate the association between interlock laws and fatal impaired-driving crashes. METHODS: Differences in three interlock laws were evaluated by comparing alcohol-impaired passenger vehicle drivers involved in fatal crashes between 2001 and 2019 in the United States across state and time. State/time differences unrelated to interlock laws were controlled for by fitting a Poisson model. The exposure measure was the number of passenger vehicle drivers in fatal crashes that did not involve impaired drivers. Laws requiring interlocks for drivers convicted of DWI covered: repeat offenders, repeat offenders and high-BAC offenders, all offenders, or none. RESULTS: The number of states with all-offender interlock laws during the study period went from three in 2001 to 29 in 2019, and the number of states with any of the three laws increased from 16 to 44. All-offender laws were associated with 26% fewer drivers with 0.08+ BAC involved in fatal crashes, compared with no law. Repeat-offender laws were associated with a 9% reduction in impaired drivers, compared with no law. Repeat and high-BAC laws were associated with a 20% reduction in impaired drivers in fatal crashes, compared with no law. CONCLUSION: Laws mandating alcohol ignition interlocks, especially those covering all offenders, are an effective impaired-driving countermeasure that reduces the number of impaired drivers in fatal crashes.
Assuntos
Intoxicação Alcoólica , Condução de Veículo , Dirigir sob a Influência , Acidentes de Trânsito , Consumo de Bebidas Alcoólicas , Humanos , Equipamentos de Proteção , Estados UnidosRESUMO
The diploid form of tall wheatgrass, Thinopyrum elongatum (Host) D.R. Dewey (2n = 2x = 14, EE genome), has a high level of resistance to fusarium head blight. The symptoms did not spread beyond the inoculated florets following point inoculation. Using a series of E-genome chromosome additions in a bread wheat cultivar Chinese Spring (CS) background, the resistance was found to be localized to the long arm of chromosome 7E. The CS mutant ph1b was used to induce recombination between chromosome 7E, present in the 7E(7D) substitution and homoeologous wheat chromosomes. Multivalent chromosome associations were detected in the BC1 hybrids, confirming the effectiveness of the ph1b mutant. Genetic markers specific for chromosome 7E were used to estimate the size of the 7E introgression in the wheat genome. Using single sequence repeat (SSR) markers specific for homoeologous wheat chromosome 7, introgressions were detected on wheat chromosomes 7A, 7B, and 7D. Some of the introgression lines were resistant to fusarium head blight.
Assuntos
Resistência à Doença/genética , Fusarium , Doenças das Plantas/genética , Poaceae , Triticum , Cromossomos de Plantas/genética , Fusarium/patogenicidade , Doenças das Plantas/microbiologia , Poaceae/genética , Triticum/genética , Triticum/microbiologiaRESUMO
The tall wheatgrass species Thinopyrum elongatum carries on the long arm of chromosome 7E, a locus that contributes strongly to resistance to fusarium head blight (FHB), a devastating fungal disease affecting wheat crops in all temperate areas of the world. Introgression of Th. elongatum 7E chromatin into chromosome 7D of wheat was induced by the ph1b mutant of CS. Recombinants between chromosome 7E and wheat chromosome 7D, induced by the ph1b mutation, were monitored by a combination of molecular markers and phenotyping for FHB resistance. Progeny of up to five subsequent generations derived from two lineages, 64-8 and 32-5, were phenotyped for FHB symptoms and genotyped using published and novel 7D- and 7E-specific markers. Fragments from the distal end of 7EL, still carrying FHB resistance and estimated to be less than 114 and 66 Mbp, were identified as introgressed into wheat chromosome arm 7DL of progeny derived from 64-8 and 32-5, respectively. Gene expression analysis revealed variation in the expression levels of genes from the distal ends of 7EL and 7DL in the introgressed progeny. The 7EL introgressed material will facilitate the use of the 7EL FHB resistance locus in wheat breeding programs.
Assuntos
Resistência à Doença/genética , Fusarium , Doenças das Plantas/genética , Poaceae , Triticum , Mapeamento Cromossômico , Cromossomos de Plantas/genética , DNA de Plantas , Fusarium/patogenicidade , Expressão Gênica , Marcadores Genéticos , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Poaceae/genética , Triticum/genéticaAssuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , COVID-19 , Teste para COVID-19 , Pré-Escolar , Infecções por Coronavirus/complicações , Exantema/etiologia , Feminino , Humanos , Masculino , New York , Pandemias , Pneumonia Viral/complicações , Reação em Cadeia da Polimerase , SARS-CoV-2 , Testes SorológicosRESUMO
Purpose: Children with Ewing sarcoma (ES) routinely undergo surveillance imaging after completion of therapy; however, the medical benefit of this imaging remains unclear. We aimed to determine whether there is a difference in survival between patients whose relapse was detected based on development of new symptoms or by routine imaging. Methods: We retrospectively reviewed all patients consecutively diagnosed with ES at Children's Healthcare of Atlanta from 2000 to 2011. Patient characteristics and outcomes were compared based on whether their relapse was diagnosed based on symptoms or by routine surveillance imaging alone. Results: Thirty-three percent (28/85) of patients relapsed. Median age at time of relapse was 15.5 years (interquartile range: 12.5-18.0). Among the relapsed patients, 57% (16/28) were symptomatic and 43% (12/28) were asymptomatic, having relapse detected on surveillance imaging alone. The most common presenting symptom was bone pain occurring in 69% (11/16) of patients. The 5-year postrelapse overall survival for patients with symptomatic relapse was 0% (95% confidence interval [CI]: not estimated) compared with 15% (95% CI: 1-48) for patients with an asymptomatic relapse (p < 0.01). After adjusting for extent of disease and time to relapse, having a symptomatic relapse was still strongly associated with a worse outcome (hazard ratio: 9.68; 95% CI: 3.09-30.34). Conclusion: Patients with ES whose relapse is detected on imaging before the development of symptoms have significantly better outcomes, suggesting a potentially beneficial role of routine surveillance imaging in this population of patients. Further prospective analyses are needed to confirm these findings, and determine the optimal evidence-based imaging modality and schedule.