Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 131
Filtrar
1.
Proc Natl Acad Sci U S A ; 117(23): 12584-12591, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-31527245

RESUMO

Cement production is currently the largest single industrial emitter of CO2, accounting for ∼8% (2.8 Gtons/y) of global CO2 emissions. Deep decarbonization of cement manufacturing will require remediation of both the CO2 emissions due to the decomposition of CaCO3 to CaO and that due to combustion of fossil fuels (primarily coal) in calcining (∼900 °C) and sintering (∼1,450 °C). Here, we demonstrate an electrochemical process that uses neutral water electrolysis to produce a pH gradient in which CaCO3 is decarbonated at low pH and Ca(OH)2 is precipitated at high pH, concurrently producing a high-purity O2/CO2 gas mixture (1:2 molar ratio at stoichiometric operation) at the anode and H2 at the cathode. We show that the solid Ca(OH)2 product readily decomposes and reacts with SiO2 to form alite, the majority cementitious phase in Portland cement. Electrochemical calcination produces concentrated gas streams from which CO2 may be readily separated and sequestered, H2 and/or O2 may be used to generate electric power via fuel cells or combustors, O2 may be used as a component of oxyfuel in the cement kiln to improve efficiency and lower CO2 emissions, or the output gases may be used for other value-added processes such as liquid fuel production. Analysis shows that if the hydrogen produced by the reactor were combusted to heat the high-temperature kiln, the electrochemical cement process could be powered solely by renewable electricity.

2.
Am J Otolaryngol ; 44(2): 103762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36628908

RESUMO

BACKGROUND: To analyze the impact of facility volume on survival for human papilloma virus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) patients. METHODS: Patients treated for HPV+ OPSCC from 2010 to 2017 were queried from the National Cancer Database. Facilities of average annual case volume <50th percentile were categorized as low-volume (LV) and >95th percentile as high-volume (HV). RESULTS: 11,546 were included, with 10,305 patients (89.3 %) treated at LV and 1241 (10.7 %) at HV facilities. A greater proportion of cases involving resection of base of tongue and lingual tonsil were treated at HV (30.3 %) compared to LV (22.3 %) facilities (p < 0.001). Patients treated at a HV facility had greater percentage of clinical T4 (11.2 % vs. 8.6 %, p = 0.001) and N+ disease (90.5 % vs. 85.7 %, p < 0.001) patients. Survival analysis showed no statistically significant difference between five-year overall survival rates by facility volume (p = 0.388) for all patients. On multivariable analysis, facility volume was not associated with survival (HR: 0.968 [0.758-1.235], p = 0.791). These trends were found for both patients undergoing primary surgery or chemoradiotherapy. CONCLUSION: Our data indicates that patients with HPV+ OPSCC do not experience a survival benefit with treatment at HV facility, suggesting these patients may be adequately treated at LV centers.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Papillomavirus Humano , Neoplasias Orofaríngeas/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Papillomaviridae , Estudos Retrospectivos
3.
Environ Sci Technol ; 56(5): 2959-2967, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35148085

RESUMO

22 alkylated polycyclic aromatic hydrocarbons (alk-PAHs) were characterized in ambient air individually for the first time in urban and semi-urban locations in Toronto, Canada. Five unsubstituted PAHs were included for comparison. Results from the measurements were used to estimate benzo[a]pyrene equivalent toxicity (BaPeq) of individual compounds in order to investigate the significance of a single compound in contributing to the overall toxic equivalency (TEQ) of air mixtures. To determine which compounds merit further investigation, BaPeq values of individual compounds were compared to the measured BaP toxicity. Our results showed that both unsubstituted and alkylated PAHs were more abundant in the urban area (38 and 30%, respectively). Benzo[a]pyrene levels at the urban location exceeded Ontario's 24 h guideline (40% of the events), and on average, it was 5 times higher than that at the semi-urban area. Gas-phase two- and three-ring compounds contributed up to 39% (urban) and 76% (semi-urban) of the TEQ of all compounds analyzed. Some alk-PAHs such as 7,12-dimethylbenzo[a]anthracene had a huge impact on the toxicity of urban air, and its BaPeq was on average 8 times higher than that of BaP. We emphasize that the toxic impact of alkylated and gaseous PAHs, which is not routinely included in many air monitoring programs, is significant and should not be neglected.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Benzo(a)pireno , Canadá , Monitoramento Ambiental/métodos , Hidrocarbonetos Policíclicos Aromáticos/análise , Receptores Proteína Tirosina Quinases
4.
Environ Sci Technol ; 55(4): 2254-2264, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33512990

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are of high concern to public health due to their carcinogenic and mutagenic properties. Here, we present the first comprehensive and quantitative analysis of sources, potential source regions according to source sectors and source-related human health risks of multi-year atmospheric measurements of PAHs in the Canadian Great Lakes Basin (GLB). The highest PAH concentrations were observed at a rural residential site (Egbert), followed by two regionally representative remote sites [Point Petre (PPT) and Burnt Island]. The levels of most PAHs in the GLB atmosphere significantly decreased between 1997 and 2017, broadly consistent with the decreasing trends of anthropogenic emissions. Coal, liquid fossil fuel, and biomass burning were the most common potential sources. The potential source regions for most source sectors were identified south or southwest of the sampling sites. Risk assessment suggests potential health risks associated with the inhalation of atmospheric PAHs. On a positive note, health risks from coal combustion, liquid fossil fuel combustion, and petrogenic sources at PPT significantly decreased, directly demonstrating the success of emission control in reducing health impacts. In contrast, the health risk from forest fire-related PAH emissions may play an increasing role in the future due to climate change.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Canadá , China , Monitoramento Ambiental , Humanos , Lagos , Hidrocarbonetos Policíclicos Aromáticos/análise
5.
Nature ; 512(7515): 449-52, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-25164756

RESUMO

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.


Assuntos
Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Cromatina/genética , Cromatina/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Animais , Linhagem Celular , Centrômero/genética , Centrômero/metabolismo , Cromatina/química , Montagem e Desmontagem da Cromatina/genética , Replicação do DNA/genética , Elementos Facilitadores Genéticos/genética , Epigênese Genética , Heterocromatina/química , Heterocromatina/genética , Heterocromatina/metabolismo , Histonas/química , Histonas/metabolismo , Humanos , Anotação de Sequência Molecular , Lâmina Nuclear/metabolismo , Nucleossomos/química , Nucleossomos/genética , Nucleossomos/metabolismo , Regiões Promotoras Genéticas/genética , Especificidade da Espécie
6.
Am J Otolaryngol ; 41(4): 102464, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32307190

RESUMO

PURPOSE: This study was done to determine the direct impact implementation of the Affordable Care Act (ACA) on patients with Head and Neck Cancer (HNCA) in states that chose to expand Medicaid compared to in states that did not, as well as assess whether this impact varied among different demographic groups. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of HNCA diagnosed from 2011 to 2014. Rates of uninsured status were compared before and after Medicaid expansion and contrasted between states that did and did not expand coverage, stratified by patient and tumor characteristics, and assessed via multivariate regression. RESULTS: Overall rates of uninsured status (UR) were decreased by 63.08% in states that expanded coverage (ES) but only by 2.6% in states that did not (NS). In NS, there was an increase in proportion of black patients who were uninsured over the study period (13.7%, p = 0.077) whereas in ES, this proportion decreased by 73.3%. When stratified by primary site, patients with laryngeal cancer had the highest UR with an increase by 16.7% in NS and a decrease by 70.5% in ES. Multivariate analysis yielded predictors of uninsured status including residence in a NS, Hispanic ethnicity, and black race. CONCLUSIONS: Implementation of the ACA resulted in expanded insurance coverage for patients diagnosed with HNCA concentrated mainly in states that expanded Medicaid coverage and for patients derived from vulnerable populations, including black and Hispanic patients. In states that did not expand Medicaid, vulnerable populations were disproportionately affected.


Assuntos
Neoplasias de Cabeça e Pescoço , Disparidades em Assistência à Saúde , Área Carente de Assistência Médica , Patient Protection and Affordable Care Act , Populações Vulneráveis , Adulto , Feminino , Humanos , Cobertura do Seguro/estatística & dados numéricos , Masculino , Medicaid , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Grupos Raciais , Sistema de Registros , Programa de SEER , Estados Unidos
7.
J Virol ; 92(20)2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30068640

RESUMO

Profound alterations in host cell nuclear architecture accompany the lytic phase of Epstein-Barr virus (EBV) infection. Viral replication compartments assemble, host chromatin marginalizes to the nuclear periphery, cytoplasmic poly(A)-binding protein translocates to the nucleus, and polyadenylated mRNAs are sequestered within the nucleus. Virus-induced changes to nuclear architecture that contribute to viral host shutoff (VHS) must accommodate selective processing and export of viral mRNAs. Here we describe additional previously unrecognized nuclear alterations during EBV lytic infection in which viral and cellular factors that function in pre-mRNA processing and mRNA export are redistributed. Early during lytic infection, before formation of viral replication compartments, two cellular pre-mRNA splicing factors, SC35 and SON, were dispersed from interchromatin granule clusters, and three mRNA export factors, Y14, ALY, and NXF1, were depleted from the nucleus. During late lytic infection, virus-induced nodular structures (VINORCs) formed at the periphery of viral replication compartments. VINORCs were composed of viral (BMLF1 and BGLF5) and cellular (SC35, SON, SRp20, and NXF1) proteins that mediate pre-mRNA processing and mRNA export. BHLF1 long noncoding RNA was invariably found in VINORCs. VINORCs did not contain other nodular nuclear cellular proteins (PML or coilin), nor did they contain viral proteins (BRLF1 or BMRF1) found exclusively within replication compartments. VINORCs are novel EBV-induced nuclear structures. We propose that EBV-induced dispersal and depletion of pre-mRNA processing and mRNA export factors during early lytic infection contribute to VHS; subsequent relocalization of these pre-mRNA processing and mRNA export proteins to VINORCs and viral replication compartments facilitates selective processing and export of viral mRNAs.IMPORTANCE In order to make protein, mRNA transcribed from DNA in the nucleus must enter the cytoplasm. Nuclear export of mRNA requires correct processing of mRNAs by enzymes that function in splicing and nuclear export. During the Epstein-Barr virus (EBV) lytic cycle, nuclear export of cellular mRNAs is blocked, yet export of viral mRNAs is facilitated. Here we report the dispersal and dramatic reorganization of cellular (SC35, SON, SRp20, Y14, ALY, and NXF1) and viral (BMLF1 and BGLF5) proteins that play key roles in pre-mRNA processing and export of mRNA. These virus-induced nuclear changes culminate in formation of VINORCs, novel nodular structures composed of viral and cellular RNA splicing and export factors. VINORCs localize to the periphery of viral replication compartments, where viral mRNAs reside. These EBV-induced changes in nuclear organization may contribute to blockade of nuclear export of host mRNA, while enabling selective processing and export of viral mRNA.


Assuntos
Núcleo Celular/virologia , Herpesvirus Humano 4/fisiologia , RNA Longo não Codificante/análise , RNA Viral/análise , Proteínas Virais/análise , Replicação Viral , Células HEK293 , Humanos , Microscopia de Fluorescência
8.
Am J Otolaryngol ; 39(5): 522-526, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29903624

RESUMO

BACKGROUND: Resident duty hour restrictions can limit the frequency of resident flap checks at smaller institutions with "home" call. Institutions are compensating with adjuvant nursing flap checks as well as incorporating technology; however, this management remains controversial. METHODS: A prospective cohort of 122 free flaps for reconstruction of the head and neck by a single surgeon. Demographic information, operative details, postoperative care, and flap outcomes were recorded. RESULTS: Over 42 months, 122 free flaps were performed on 115 patients. The overall flap success rate was 96%. The flap success rate at 72 h was 98% and 96% at the time of discharge with reexploration rates of 11.6%. The intraoperative and postoperative salvage rates were 71% and 64.3% respectively. CONCLUSION: Limited resident flap checks combined hourly nurse flap checks and an implantable Doppler is an effective monitoring protocol for academic programs in the setting of residency duty hour restrictions.


Assuntos
Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/cirurgia , Monitorização Fisiológica/métodos , Procedimentos de Cirurgia Plástica/educação , Estudos de Coortes , Bases de Dados Factuais , Educação de Pós-Graduação em Medicina/métodos , Feminino , Seguimentos , Retalhos de Tecido Biológico/transplante , Sobrevivência de Enxerto , Hospitais Universitários , Humanos , Internato e Residência/métodos , Masculino , Cuidados Pós-Operatórios/normas , Cuidados Pós-Operatórios/tendências , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Microsurgery ; 38(5): 504-511, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29218804

RESUMO

OBJECTIVE: Diabetes is associated with microvascular pathology and may predispose patients undergoing microvascular surgery to complications. This study assesses diabetes as a risk factor for complications following free flap surgery of the head and neck. PATIENTS AND METHODS: In this retrospective cohort study, data on free flap surgeries of the head and neck between 2005 and 2014 was collected from the National Surgical Quality Improvement Program (NSQIP) database. A propensity-matching algorithm (PSM) was used to equilibrate distribution of numerous covariates between the diabetic and nondiabetic cohorts. A sub-analysis was performed to examine the impact of insulin-dependency. RESULTS: The initial dataset contained 2187 free flaps of the head and neck. After implementing PSM, a new population was created containing 506 total cases with 253 DM patients. The majority of cases were male and white. The matched cohort did not contain any demographics or comorbidities associated with DM. Complications significantly elevated in the DM group were severe bleeding (P = .046), postoperative ventilation greater than 48 hours (P < .001), and pneumonia (P < .048). In patients with insulin-dependent diabetes, reintubation (P = .005), cardiac arrest (P = .010), severe bleeding (P = .006), overall surgical complications (P = .015), and overall complications (P = .005) were significantly increased. CONCLUSION: This study examines the impact of diabetes on postoperative complications following free flap reconstruction of the head and neck. Propensity score matching was utilized. Analysis of the PSM cohort suggests that diabetic patients have elevated rates of postoperative pulmonary complications. Additionally, patients with insulin-dependent diabetes have significantly elevated rates of medical and surgical complications.


Assuntos
Complicações do Diabetes/epidemiologia , Retalhos de Tecido Biológico/transplante , Cabeça/cirurgia , Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Pneumonia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mineração de Dados , Bases de Dados Factuais , Feminino , Sobrevivência de Enxerto , Hemorragia/etiologia , Humanos , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Pneumonia/terapia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Ventilação Pulmonar , Estudos Retrospectivos , Fatores de Risco
10.
Nature ; 471(7339): 480-5, 2011 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-21179089

RESUMO

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.


Assuntos
Cromatina/genética , Cromatina/metabolismo , Drosophila melanogaster/genética , Animais , Linhagem Celular , Imunoprecipitação da Cromatina , Proteínas Cromossômicas não Histona/análise , Proteínas Cromossômicas não Histona/metabolismo , Desoxirribonuclease I/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Éxons/genética , Regulação da Expressão Gênica/genética , Genes de Insetos/genética , Genoma de Inseto/genética , Histonas/química , Histonas/metabolismo , Masculino , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Complexo Repressor Polycomb 1 , RNA/análise , RNA/genética , Análise de Sequência , Transcrição Gênica/genética
11.
Am J Otolaryngol ; 38(5): 560-564, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28716300

RESUMO

OBJECTIVES: Analyze postoperative complications after free flap surgery based on PGY training level. METHODS: Data on free flap surgeries of the head and neck performed from 2005 to 2013 was collected from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Cases identifying the status of resident participation in the surgery and the PGY level were included. RESULTS: There were 582 cases with primary surgeon data available. 63 cases were performed with a junior resident, 211 were performed with the assistance of a senior resident, 279 cases were performed with a fellow, and 29 cases were performed by an attending alone without resident involvement. The overall complication rate was 55.2%. There was no statistically significant difference in the rate of complications between groups (47.6%, 59.7%, 53.0%, 58.6%, p=0.277). After controlling for all confounding variables using multivariate analysis there was no significant difference in morbidity, mortality, readmissions, and reoperation amongst the groups. Furthermore, when comparing resident versus fellow involvement using multivariate analysis there were no significant differences in morbidity (OR=0.768[0.522-1.129]), mortality (OR=1.489[0.341-6.499]), readmissions (OR=1.018[0.458-2.262]), and reoperation (OR=0.863[0.446-1.670]). CONCLUSION: Resident and fellow participation in microvascular reconstructive cases does not appear to increase 30-day rates of medical, surgical, or overall complications.


Assuntos
Competência Clínica , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Internato e Residência , Procedimentos de Cirurgia Plástica/educação , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade , Procedimentos de Cirurgia Plástica/efeitos adversos , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
12.
J Appl Res Intellect Disabil ; 30(2): 408-415, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26864714

RESUMO

BACKGROUND: Providers of supported living services to adults with intellectual disabilities (IDs) in the United Kingdom have procedures in place to monitor injuries; this provides opportunity to learn about the injuries being reported and recorded. The aim was to determine the incidence, causes and types of injuries experienced by 593 adults with intellectual disabilities who live with paid support in a 12-month period. METHOD: Injury data, collected via a standard electronic injury monitoring system, were compared with data collected for a matched sample of the general population in the same year. RESULTS: The adults with intellectual disabilities experienced a higher rate of injury. Falls were the commonest cause of injury for both samples, but significantly more so for the adults with intellectual disabilities. CONCLUSIONS: The higher rate of injuries, particularly minor injuries, being reported suggests a culture of injury reporting and recording within these supported living services. Electronic injury monitoring is recommended for organizations providing supported living services for adults with intellectual disabilities.

13.
Genome Res ; 23(2): 217-27, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23132910

RESUMO

A large database of copy number profiles from cancer genomes can facilitate the identification of recurrent chromosomal alterations that often contain key cancer-related genes. It can also be used to explore low-prevalence genomic events such as chromothripsis. In this study, we report an analysis of 8227 human cancer copy number profiles obtained from 107 array comparative genomic hybridization (CGH) studies. Our analysis reveals similarity of chromosomal arm-level alterations among developmentally related tumor types as well as a number of co-occurring pairs of arm-level alterations. Recurrent ("pan-lineage") focal alterations identified across diverse tumor types show an enrichment of known cancer-related genes and genes with relevant functions in cancer-associated phenotypes (e.g., kinase and cell cycle). Tumor type-specific ("lineage-restricted") alterations and their enriched functional categories were also identified. Furthermore, we developed an algorithm for detecting regions in which the copy number oscillates rapidly between fixed levels, indicative of chromothripsis. We observed these massive genomic rearrangements in 1%-2% of the samples with variable tumor type-specific incidence rates. Taken together, our comprehensive view of copy number alterations provides a framework for understanding the functional significance of various genomic alterations in cancer genomes.


Assuntos
Aberrações Cromossômicas , Genômica , Neoplasias/genética , Análise por Conglomerados , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Estudos de Associação Genética , Loci Gênicos , Instabilidade Genômica , Humanos
14.
Proc Natl Acad Sci U S A ; 110(20): 8176-81, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23625009

RESUMO

ZEBReplication Activator (ZEBRA), a viral basic zipper protein that initiates the Epstein-Barr viral lytic cycle, binds to DNA and activates transcription through heptamer ZEBRA response elements (ZREs) related to AP-1 sites. A component of the biologic action of ZEBRA is attributable to binding methylated CpGs in ZREs present in the promoters of viral lytic cycle genes. Residue S186 of ZEBRA, Z(S186), which is absolutely required for disruption of latency, participates in the recognition of methylated DNA. We find that mutant cellular AP-1 proteins, Jun(A266S) and Fos(A151S), with alanine-to-serine substitutions homologous to Z(S186), exhibit altered DNA-binding affinity and preferentially bind methylated ZREs. These mutant AP-1 proteins acquire functions of ZEBRA; they activate expression of many viral early lytic cycle gene transcripts in cells harboring latent EBV but are selectively defective in activating expression of some viral proteins and are unable to promote viral DNA replication. Transcriptional activation by mutant c-Jun and c-Fos that have acquired the capacity to bind methylated CpG challenges the paradigm that DNA methylation represses gene expression.


Assuntos
Metilação de DNA , Herpesvirus Humano 4/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transativadores/metabolismo , Latência Viral , Sequência de Aminoácidos , Linfoma de Burkitt/metabolismo , Linhagem Celular Tumoral , Regulação Viral da Expressão Gênica , Células HEK293 , Humanos , Dados de Sequência Molecular , Mutação , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética
15.
Am J Otolaryngol ; 37(5): 398-406, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27452125

RESUMO

PURPOSE: Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm of secretory glands of the upper aerodigestive tract. It accounts for 3-5% of head and neck malignancies and most commonly arises from the minor salivary glands of the oral cavity. The clinical behavior of ACC from specific anatomic subsites, including the oral cavity, is not well described in the literature. We aim to elucidate patient demographics, clinicopathologic features, incidence, and survival trends for oral cavity ACC (OCACC). METHODS: Retrospective population-based analysis of OCACC in the SEER database between 1973 and 2012. RESULTS: 1066 OCACC patients were identified, of which 57.7% were female (P<0.0001). Incidence was 0.049 per 100,000. Whites were most commonly affected (81.1%). The hard palate was the most commonly involved subsite (44.1%). Nodal involvement was seen in 8.4% of cases and distant metastasis was present in 6.2% of cases at the time of presentation. Disease-specific survival (DSS) rates at 1, 5, 10, 15, and 20years were 97.4%, 83.9%, 69.9%, 57.6%, and 46.2%, respectively. Females had a higher 5-year DSS (87.8%) than males (78.4%, P=0.0004). Cases treated with surgery had a favorable prognosis regardless of whether they received radiotherapy (P<0.0001). Nodal involvement reduced 5-year DSS by 51.6% (P<0.0001), while distant metastasis reduced 5-year DSS by 46.4% (P<0.0001). CONCLUSIONS: OCACC is a rare malignancy with females and whites being more commonly affected. At presentation, regional and distant metastases are uncommon. Poor prognostic indicators include male gender, nonsurgical therapy, nodal involvement, and distant metastasis.


Assuntos
Carcinoma Adenoide Cístico/epidemiologia , Neoplasias Bucais/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/patologia , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Gradação de Tumores , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
16.
Mol Cancer ; 14: 25, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25644941

RESUMO

BACKGROUND: Copy number variations (CNVs) are increasingly recognized as significant disease susceptibility markers in many complex disorders including cancer. The availability of a large number of chromosomal copy number profiles in both malignant and normal tissues in cancer patients presents an opportunity to characterize not only somatic alterations but also germline CNVs, which may confer increased risk for cancer. RESULTS: We explored the germline CNVs in five cancer cohorts from the Cancer Genome Atlas (TCGA) consisting of 351 brain, 336 breast, 342 colorectal, 370 renal, and 314 ovarian cancers, genotyped on Affymetrix SNP6.0 arrays. Comparing these to ~3000 normal controls from another study, our case-control association study revealed 39 genomic loci (9 brain, 3 breast, 4 colorectal, 11 renal, and 12 ovarian cancers) as potential candidates of tumor susceptibility loci. Many of these loci are new and in some cases are associated with a substantial increase in disease risk. The majority of the observed loci do not overlap with coding sequences; however, several observed genomic loci overlap with known cancer genes including RET in brain cancers, ERBB2 in renal cell carcinomas, and DCC in ovarian cancers, all of which have not been previously associated with germline changes in cancer. CONCLUSIONS: This large-scale genome-wide association study for CNVs across multiple cancer types identified several novel rare germline CNVs as cancer predisposing genomic loci. These loci can potentially serve as clinically useful markers conferring increased cancer risk.


Assuntos
Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença/genética , Neoplasias/genética , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Risco
17.
Am J Gastroenterol ; 109(2): 250-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24419480

RESUMO

OBJECTIVES: Constipation is one of the most common outpatient diagnoses in primary care and gastroenterology clinics; however, there is limited data on the inpatient burden of constipation in the United States. The aim of this study was to evaluate inpatient admission rates, length of stay, and associated costs related to constipation from 1997 to 2010. METHODS: We analyzed the National Inpatient Sample Database for all patients in which constipation (ICD-9 codes: 564.0-564.09) was the principal discharge diagnosis from 1997 to 2010. The statistical significance of the difference in the number of hospital discharges, length of stay, and hospital costs over the study period was determined by utilizing the Spearman's coefficient to describe various trends. RESULTS: Between 1997 and 2010, the number of hospitalizations for patients with a primary discharge diagnosis of constipation increased from 21,190 patients to 48,450 (P<0.001, GoF test), whereas the mean length of hospital stay increased only slightly from 3.0 days to 3.1 days (b=0.008 (0.003-0.014); P=0.004). The mean charges per hospital discharge for constipation increased from $8869 in 1997 (adjusted for long-term inflation) to $17,518 in 2010 (b=745.4 (685.3-805.6); P<0.001)), whereas the total costs increased from $188,109,249 (adjusted for inflation) in 1997 to $851,713,263 in 2010. Although the elderly (65-84 years) accounted for the largest percentage of constipation discharges, patients in the 1-17 years age group had the highest frequency of constipation per 10,000 discharges. CONCLUSIONS: The number of inpatient discharges for constipation and associated costs has significantly increased between 1997 and 2010.


Assuntos
Constipação Intestinal/economia , Custos Hospitalares , Hospitalização/economia , Tempo de Internação/economia , Alta do Paciente/economia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos de Coortes , Constipação Intestinal/diagnóstico , Constipação Intestinal/terapia , Bases de Dados Factuais , Feminino , Custos de Cuidados de Saúde , Hospitalização/tendências , Humanos , Pacientes Internados/estatística & dados numéricos , Tempo de Internação/tendências , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Alta do Paciente/tendências , Distribuição de Poisson , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Estados Unidos
18.
Artigo em Inglês | MEDLINE | ID: mdl-38752769

RESUMO

BACKGROUND AND IMPORTANCE: Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. CLINICAL PRESENTATION: An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. CONCLUSION: This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.

19.
Laryngoscope ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895869

RESUMO

OBJECTIVES: Changing location of postoperative radiotherapy (PORT) after treatment at a high-volume facility (HVF) is associated with worse survival in various head and neck cancers. Our study investigates this relationship in salivary gland cancer (SGC). METHODS: The 2004-2016 National Cancer Database was queried for all cases of adult SGC treated with surgery and PORT with or without adjuvant chemotherapy. Patients with multiple cancer diagnoses, metastatic disease, or unknown PORT facility were excluded. Reporting facilities with >95th percentile annual case volume were classified as HVFs, the remainder were classified low-volume facilities (LVFs). RESULTS: A total of 7885 patients met inclusion criteria, of which 418 (5.3%) were treated at an HVF. Patients treated at an HVF had higher rates clinical nodal positivity (18.2% vs. 14.0%, p < 0.001) and clinical T3/T4 (27.3% vs. 20.7%, p = 0.001) disease. Patients at HVFs changed facility for PORT at lower rates (18.9% vs. 24.5%, p = 0.009). Patients treated at an HVF had higher 5-year overall survival (5-OS) than those treated at an LVF (79.0% vs. 72.0%, p = 0.042). Patients treated at an HVF that changed PORT facility had worse 5-OS (60.8% vs. 83.2%, p < 0.001). Radiation facility change was an independent predictor of worse survival in patients treated at an HVF (HR: 8.99 [3.15-25.67], p < 0.001) but not for patients treated at a LVF (HR: 1.11 [0.98-1.25], p = 0.109). CONCLUSIONS: Patients treated at an HVF changing facility for PORT for SGC experience worse survival. Our data suggest patients treated surgically at an HVF should be counseled to continue their PORT at the same institution. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

20.
PLoS One ; 19(4): e0293861, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603714

RESUMO

The goal of this study was to characterize the bacterial diversity on different melon varieties grown in different regions of the US, and determine the influence that region, rind netting, and variety of melon has on the composition of the melon microbiome. Assessing the bacterial diversity of the microbiome on the melon rind can identify antagonistic and protagonistic bacteria for foodborne pathogens and spoilage organisms to improve melon safety, prolong shelf-life, and/or improve overall plant health. Bacterial community composition of melons (n = 603) grown in seven locations over a four-year period were used for 16S rRNA gene amplicon sequencing and analysis to identify bacterial diversity and constituents. Statistically significant differences in alpha diversity based on the rind netting and growing region (p < 0.01) were found among the melon samples. Principal Coordinate Analysis based on the Bray-Curtis dissimilarity distance matrix found that the melon bacterial communities clustered more by region rather than melon variety (R2 value: 0.09 & R2 value: 0.02 respectively). Taxonomic profiling among the growing regions found Enterobacteriaceae, Bacillaceae, Microbacteriaceae, and Pseudomonadaceae present on the different melon rinds at an abundance of ≥ 0.1%, but no specific core microbiome was found for netted melons. However, a core of Pseudomonadaceae, Bacillaceae, and Exiguobacteraceae were found for non-netted melons. The results of this study indicate that bacterial diversity is driven more by the region that the melons were grown in compared to rind netting or melon type. Establishing the foundation for regional differences could improve melon safety, shelf-life, and quality as well as the consumers' health.


Assuntos
Bacillaceae , Cucumis melo , Cucurbitaceae , Estados Unidos , Cucurbitaceae/microbiologia , Cucumis melo/microbiologia , RNA Ribossômico 16S/genética , Bactérias/genética , Enterobacteriaceae
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa