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1.
J Antimicrob Chemother ; 76(8): 2204-2212, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33895844

RESUMO

OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat a variety of infections. However, hospital readmissions remain relatively common. We examined the external validity and clinical usefulness of a previously derived risk prediction model for 30 day unplanned hospitalization in patients receiving OPAT. METHODS: A retrospective cohort study was conducted at two large teaching hospitals in the UK. The design comprised quasi-external temporal validation on patients from the same OPAT setting as the model development, and broader external validation on patients from a different setting. The model predictors were age, prior hospitalizations in the preceding 12 months, Charlson comorbidity score, concurrent IV antimicrobial therapy, type of infection and mode of OPAT treatment. Discriminative ability, calibration and clinical usefulness were assessed. RESULTS: Data from 2578 OPAT patients were analysed. The rates of 30 day unplanned hospitalization were 11.5% (123/1073), 12.9% (140/1087) and 25.4% (106/418) in the model derivation, temporal validation and broader external validation cohorts, respectively. The discriminative ability of the prediction model was adequate on temporal validation (c-statistic 0.75; 95% CI: 0.71-0.79) and acceptable on broader validation (c-statistic 0.67; 95% CI: 0.61-0.73). In both external cohorts, the model displayed excellent calibration between observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds. CONCLUSIONS: A simple risk prediction model for unplanned readmission in OPAT patients demonstrated reproducible predictive performance, broad clinical transportability and clinical usefulness. This model may help improve OPAT outcomes through better identification of high-risk patients and provision of tailored care.


Assuntos
Anti-Infecciosos , Pacientes Ambulatoriais , Assistência Ambulatorial , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Hospitalização , Humanos , Lactente , Infusões Parenterais , Estudos Retrospectivos
2.
PLoS Pathog ; 13(11): e1006708, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29099869

RESUMO

Avian leukosis virus (ALV) is a simple retrovirus that causes a wide range of tumors in chickens, the most common of which are B-cell lymphomas. The viral genome integrates into the host genome and uses its strong promoter and enhancer sequences to alter the expression of nearby genes, frequently inducing tumors. In this study, we compare the preferences for ALV integration sites in cultured cells and in tumors, by analysis of over 87,000 unique integration sites. In tissue culture we observed integration was relatively random with slight preferences for genes, transcription start sites and CpG islands. We also observed a preference for integrations in or near expressed and spliced genes. The integration pattern in cultured cells changed over the course of selection for oncogenic characteristics in tumors. In comparison to tissue culture, ALV integrations are more highly selected for proximity to transcription start sites in tumors. There is also a significant selection of ALV integrations away from CpG islands in the highly clonally expanded cells in tumors. Additionally, we utilized a high throughput method to quantify the magnitude of clonality in different stages of tumorigenesis. An ALV-induced tumor carries between 700 and 3000 unique integrations, with an average of 2.3 to 4 copies of proviral DNA per infected cell. We observed increasing tumor clonality during progression of B-cell lymphomas and identified gene players (especially TERT and MYB) and biological processes involved in tumor progression.


Assuntos
Vírus da Leucose Aviária , Linfoma de Células B/virologia , Regiões Promotoras Genéticas , Integração Viral/genética , Animais , Carcinogênese , Galinhas , Células Clonais/virologia , Provírus/genética
3.
Pediatr Radiol ; 47(6): 651-656, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28265695

RESUMO

BACKGROUND: Pediatric interventional radiology is a distinct subspecialty differing from both pediatric diagnostic radiology and adult interventional radiology. We conducted a workforce survey in 2005 to evaluate the state of pediatric interventional radiology at that time. Since then there have been many advancements to the subspecialty, including the founding of the Society for Pediatric Interventional Radiology (SPIR). OBJECTIVE: To evaluate the current state of the pediatric interventional radiology workforce and compare findings with those of the initial 2005 workforce survey. MATERIALS AND METHODS: We sent a two-part survey electronically to members of SPIR, the Society for Pediatric Radiology (SPR), the Society of Chairmen of Radiology in Children's Hospitals (SCORCH) and the Society of Interventional Radiology (SIR). Part 1 focused on individual practitioners (n=177), while part 2 focused on group practices and was answered by a leader from each group (n=88). We examined descriptive statistics and, when possible, compared the results to the study from 2005. RESULTS: A total of 177 individuals replied (a 331% increase over the first study) and 88 pediatric interventional radiology (IR) service sites responded (a 131.6% increase). Pediatric IR has become a more clinically oriented specialty, with a statistically significant increase in services with admitting privileges, clinics and performance of daily rounds. Pediatric IR remains diverse in training and practice. Many challenges still exist, including anesthesia/hospital support, and the unknown impact of the new IR residency on pediatric IR training, although the workforce shortage has been somewhat alleviated, as demonstrated by the decreased mean call from 165 days/year to 67.2 days/year. CONCLUSION: Pediatric interventional radiology practitioners and services have grown significantly since 2005, although the profile of this small subspecialty has changed and some challenges remain.


Assuntos
Pediatria , Radiologia Intervencionista , Seguimentos , Humanos , Internacionalidade , Inquéritos e Questionários , Recursos Humanos
4.
J Virol ; 89(9): 4712-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25673726

RESUMO

UNLABELLED: Avian leukosis virus subgroup J (ALV-J) is a simple retrovirus that can cause hemangiomas and myeloid tumors in chickens and is currently a major economic problem in Asia. Here we characterize ALV-J strain PDRC-59831, a newly studied U.S. isolate of ALV-J. Five-day-old chicken embryos were infected with this virus, and the chickens developed myeloid leukosis and hemangiomas within 2 months after hatching. To investigate the mechanism of pathogenesis, we employed high-throughput sequencing to analyze proviral integration sites in these tumors. We found expanded clones with integrations in the MET gene in two of the five hemangiomas studied. This integration locus was not seen in previous work characterizing ALV-J-induced myeloid leukosis. MET is a known proto-oncogene that acts through a diverse set of signaling pathways and is involved in many neoplasms. We show that tumors harboring MET integrations exhibit strong overexpression of MET mRNA. IMPORTANCE: These data suggest that ALV-J induces oncogenesis by insertional mutagenesis, and integrations in the MET oncogene can drive the overexpression of MET and contribute to the development of hemangiomas.


Assuntos
Vírus da Leucose Aviária/fisiologia , Leucose Aviária/virologia , Hemangioma/virologia , Proteínas Proto-Oncogênicas c-met/genética , Integração Viral , Animais , Vírus da Leucose Aviária/isolamento & purificação , Galinhas , Sequenciamento de Nucleotídeos em Larga Escala , Estados Unidos
5.
Plants (Basel) ; 12(18)2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37765381

RESUMO

The transition from annual to perennial growth habits can contribute to increased sustainability and diversification of staple cropping systems like those based on annual wheat. Amphiploids between Triticum aestivum and Thinopyrum spp. can present a wheat-like morphology and post sexual cycle regrowth. The complex and unpredictable nature of the chromosomal rearrangements typical of inter-generic hybrids can hamper progress in the development of this new crop. By using fluorescence in situ hybridization, we described the genomic constitution of three perennial wheat breeding lines that regrew and completed a second year of production in field conditions in Washington state (USA). Two breeding lines presented stable, 56-chromosome partial amphiploids; however, their chromosome composition differed significantly. The third breeding line presented an unstable karyotype with a chromosome number ranging from 53 to 58 across eight individuals. The agronomic performance of the perennial breeding lines was evaluated for two growing seasons from 2020 to 2022. The grain yields of the perennial lines were lower than the grain production of the annual wheat control line in the first season. The perennial lines displayed vigorous regrowth after the initial harvest; however, worsening environmental conditions in the second season of growth hampered subsequent growth and grain yield. This information facilitates the breeding work necessary to improve key traits by grouping agronomically valuable individuals according to their genomic constitution.

6.
Biochim Biophys Acta ; 1809(11-12): 654-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21683170

RESUMO

MicroRNAs have been reported for the avian herpesviruses Marek's disease virus 1 (MDV1; oncogenic), Marek's disease virus 2 (MDV2; non-oncogenic), herpesvirus of turkeys (HVT), and infectious laryngotracheitis virus (ILTV). No obvious phylogenetic relationships exist among the avian herpesvirus microRNAs, but the general genomic locations of microRNA clusters are conserved, with microRNAs being located in the repeat regions of the genomes. In some cases, microRNAs are antisense to open reading frames. Among MDV1 field isolates with different virulence properties, microRNAs are highly conserved, and variations that have been observed lie in putative promoter regions. One cluster of MDV1 microRNAs lies upstream of the meq gene, and this cluster is more highly expressed in tumors caused by an extremely virulent MDV1 isolate compared to tumors caused by a less virulent isolate. Several of the avian herpesvirus microRNAs are orthologs of microRNAs in other species. For example, mdv1-miR-M4 shares a seed sequence with gga-miR-155 (also shared with Kaposi sarcoma herpesvirus (KSHV) kshv-miR-K12), mdv2-miR-M21 shares a seed with miR-29b, and hvt-miR-H14 shares a seed sequence with miR-221. Functional analyses of avian herpesvirus microRNAs include a variety of in vitro assays to demonstrate potential function as well as the use of mutants that can exploit the ability to assess phenotypes experimentally in the natural host. This article is part of a Special Issue entitled:MicroRNA's in viral gene regulation.


Assuntos
Transformação Celular Neoplásica/genética , Herpesvirus Galináceo 2/genética , MicroRNAs/metabolismo , Latência Viral/genética , Animais , Galinhas/virologia , Genoma Viral , Herpesvirus Galináceo 2/classificação , Herpesvirus Galináceo 2/fisiologia , MicroRNAs/genética , Filogenia , Perus/virologia
7.
J Infect ; 83(6): 644-649, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34614400

RESUMO

OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat infective endocarditis (IE) with documented success. This study aims to identify risk factors for treatment failure and poor outcomes in patients with IE treated through OPAT. METHODS: We conducted a retrospective analysis of all episodes of IE treated over 13 years (September 2006 - September 2019) at a large teaching hospital in Sheffield, UK. We defined OPAT failure as unplanned readmission or death within 30 days of discharge from the OPAT service. Major adverse cardiac events (MACE) were defined as a composite of IE-related death, cardiac surgery, and recurrence of IE within the first year of completion of OPAT. RESULTS: Overall, 168 episodes of IE were reviewed. OPAT failure and MACE occurred in 44 episodes (26.2%) and 29 episodes (17.3%) respectively. On multivariable analysis, pre-existing renal failure (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.08-8.30; P = 0.034) and Charlson comorbidity score (aOR, 1.29 per unit increase; 95% CI, 1.06-1.57; P = 0.011) were associated with increased risk of failure. Previous endocarditis (aOR, 3.60; 95% CI, 1.49-8.70; P = 0.004) and cardiac complications (aOR, 3.85; 95% CI, 1.49-9.93; P = 0.005) were risk factors for MACE, whereas cardiac surgery during the initial hospitalisation for IE (aOR, 0.34; 95% CI, 0.12-0.22; P < 0.001) was a protective factor. CONCLUSIONS: Our findings suggest that OPAT is safe and effective for completing antibiotic treatment for IE, including cases deemed to be at increased risk of complications. However, careful patient selection and monitoring of patients with pre-existing comorbidities and cardiac complications are recommended to optimise clinical outcomes.


Assuntos
Endocardite Bacteriana , Endocardite , Assistência Ambulatorial , Antibacterianos/uso terapêutico , Endocardite/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Humanos , Pacientes Ambulatoriais , Estudos Retrospectivos
8.
J Virol ; 82(24): 12213-20, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18842708

RESUMO

Marek's disease virus (MDV), a herpesvirus that causes a lymphoproliferative disorder in chickens, encodes a number of microRNAs derived primarily from two locations in the MDV genome. One cluster of microRNA genes flanks the meq oncogene, and a second cluster is found within the latency-associated transcript (LAT) region. The sequences of MDV microRNAs from a collection of field and reference strains with various levels of virulence were compared and found to be highly conserved. However, microRNAs from the meq cluster were detected at higher levels in lymphomas caused by a form of the virus designated very virulent plus (vv+; strain 615K, also known as T. King) than in those caused by a less virulent (very virulent [vv]) form (RB1B). For example, levels of mdv1-miR-M4, which shares a seed sequence with miR-155, a microRNA implicated in B-cell lymphoma, were threefold higher and levels of mdv1-miR-M2*/3p were more than sixfold higher in vv+ MDV-induced tumors than in vv MDV-induced tumors. In contrast, levels of the microRNAs from the LAT cluster were equivalent in tumors produced by vv and vv+ strains. Additionally, mdv1-miR-M4 is the MDV microRNA most highly expressed in tumors, where it accounts for 72% of all MDV microRNAs, as determined by deep sequencing. These data suggest that the meq cluster microRNAs play an important role in the pathogenicity of MDV.


Assuntos
Regulação Viral da Expressão Gênica , Herpesvirus Galináceo 2/genética , Herpesvirus Galináceo 2/metabolismo , MicroRNAs/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Galinhas , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/virologia
9.
BMC Genomics ; 9: 185, 2008 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-18430245

RESUMO

BACKGROUND: The use of new, deep sequencing technologies has greatly accelerated microRNA discovery. We have applied this approach to the identification of chicken microRNAs and to the comparison of microRNAs in chicken embryo fibroblasts (CEF) infected with Marek's disease virus (MDV) to those present in uninfected CEF. RESULTS: We obtained 125,463 high quality reads that showed an exact match to the chicken genome. The majority of the reads corresponded to previously annotated chicken microRNAs; however, the sequences of many potential novel microsRNAs were obtained. A comparison of the reads obtained in MDV-infected and uninfected CEF indicates that infection does not significantly perturb the expression profile of microRNAs. Frequently sequenced microRNAs include miR-221/222, which are thought to play a role in growth and proliferation. A number of microRNAs (e.g., let-7, miR-199a-1, 26a) are expressed at lower levels in MDV-induced tumors, highlighting the potential importance of this class of molecules in tumorigenesis. CONCLUSION: Deep sequencing technology is highly suited for small RNA discovery. This approach is independent of comparative sequence analysis, which has been the primary method used to identify chicken microRNAs. Our results have confirmed the expression of many microRNAs identified by sequence similarity and identified a pool of candidate novel microRNAs.


Assuntos
Galinhas/genética , MicroRNAs/genética , Animais , Embrião de Galinha , Fibroblastos/metabolismo , Fibroblastos/virologia , Perfilação da Expressão Gênica , Herpesvirus Galináceo 2/genética , Doença de Marek/genética , Doenças das Aves Domésticas/genética , RNA Viral/genética
10.
Parkinsonism Relat Disord ; 48: 45-50, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29273434

RESUMO

OBJECTIVE: To examine sex differences and trends in comorbid disease and health care utilization in individuals with newly diagnosed Parkinson disease (PD). DESIGN: Retrospective cohort study. PARTICIPANTS: Over 133,000 Medicare beneficiaries with a new PD diagnosis in 2002 followed through 2008. METHODS: We compared the prevalence and cumulative incidence of common medical conditions, trends in survival and health care utilization between men and women with PD. RESULTS: Female PD patients had higher adjusted incidence rate ratio (IRR) of depression (IRR: 1.28, 1.25-1.31), hip fracture (IRR: 1.51, 1.45-1.56), osteoporosis (3.01, 2.92-3.1), and rheumatoid/osteoarthritis (IRR: 1.47, 1.43-1.51) than men. In spite of greater survival, women with PD used home health and skilled nursing facility care more often, and had less outpatient physician contact than men throughout the study period. CONCLUSIONS: Women experience a unique health trajectory after PD diagnosis as suggested by differing comorbid disease burden and health care utilization compared to men. Future studies of sex differences in care needs, care quality, comorbidity related disability, PD progression, and non-clinical factors associated with disability are needed to inform research agendas and clinical guidelines that may improve quality survival for women with PD.


Assuntos
Pessoas com Deficiência , Disparidades em Assistência à Saúde , Doença de Parkinson , Aceitação pelo Paciente de Cuidados de Saúde , Caracteres Sexuais , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Medicare , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Prevalência , Estados Unidos/epidemiologia
11.
Physiol Genomics ; 25(3): 514-24, 2006 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-16554550

RESUMO

Its accessibility, unique evolutionary position, and recently assembled genome sequence have advanced the chicken to the forefront of comparative genomics and developmental biology research as a model organism. Several chicken expressed sequence tag (EST) projects have placed the chicken in 10th place for accrued ESTs among all organisms in GenBank. We have completed the single-pass 5'-end sequencing of 37,557 chicken cDNA clones from several single and multiple tissue cDNA libraries and have entered 35,407 EST sequences into GenBank. Our chicken EST sequences and those found in public databases (on July 1, 2004) provided a total of 517,727 public chicken ESTs and mRNAs. These sequences were used in the CAP3 assembly of a chicken gene index composed of 40,850 contigs and 79,192 unassembled singlets. The CAP3 contigs show a 96.7% match to the chicken genome sequence. The University of Delaware (UD) EST collection (43,928 clones) was assembled into 19,237 nonredundant sequences (13,495 contigs and 5,742 unassembled singlets). The UD collection contains 6,223 unique sequences that are not found in other public EST collections but show a 76% match to the chicken genome sequence. Our chicken contig and singlet sequences were annotated according to the highest BlastX and/or BlastN hits. The UD CAP3 contig assemblies and singlets are searchable by nucleotide sequence or key word (http://cogburn.dbi.udel.edu), and the cDNA clones are readily available for distribution from the chick EST website and clone repository (http://www.chickest.udel.edu). The present paper describes the construction and normalization of single and multiple tissue chicken cDNA libraries, high-throughput EST sequencing from these libraries, the CAP3 assembly of a chicken gene index from all public ESTs, and the identification of several nonredundant chicken gene sets for production of custom DNA microarrays.


Assuntos
Galinhas/genética , Etiquetas de Sequências Expressas , Genoma , Animais , Análise por Conglomerados , Mapeamento de Sequências Contíguas , Bases de Dados Genéticas , Biblioteca Gênica , Alinhamento de Sequência , Análise de Sequência de DNA
12.
Pediatr Neurol ; 55: 22-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26597039

RESUMO

OBJECTIVE: To describe and analyze the chronological evolution of the radiological findings in seven children with febrile infection-related epilepsy syndrome. METHODS: This is a retrospective study describing the radiological findings and evolution in seven children with febrile infection-related epilepsy syndrome who presented from 2009 to 2013. The children all fit the defined clinical criteria for febrile infection-related epilepsy syndrome; all had a history of normal psychomotor development who presented with acute-onset catastrophic partial status epilepticus associated with a febrile illness or unspecific infectious process. The children were identified from the author's weekly review of the pediatric inpatient service, and then the data were collected and analyzed retrospectively. RESULTS: Six males and one female ranging from 3 months to 9 years of age presented with status epilepticus preceded by a febrile illness. Extensive investigations for infectious, autoimmune, and metabolic etiologies were unremarkable. Multiple antiepileptic medications were attempted, including drug-induced coma in all of them, with poor response. Immunotherapy with intravenous steroids or intravenous immunoglobulin (three patients had both) was tried in six of seven patients with a poor response. Ketogenic diet was initiated in four of seven patients with limited response. Serial magnetic resonance imaging studies, done from the initial presentation through 18 months of follow-up, showed evolution from normal imaging to severe cerebral atrophy. Progressive cytotoxic edema involving mostly bilateral hippocampi and temporal lobes was appreciated in one to three weeks. At one month from seizure onset, mild to moderate cerebral atrophy and hippocampal sclerosis was appreciated that continued to progress over the next year. After six to twelve months, most of the patients showed moderate to severe cerebral atrophy and by one year, cerebellar atrophy was also appreciated. CONCLUSION: Febrile infection-related epilepsy syndrome is a devastating epilepsy syndrome of childhood without a diagnostic biologic marker. The magnetic resonance imaging findings appear to be progressive and typical. Thus, combined with the clinical course, imaging findings can help to confirm the diagnosis (until a biologic marker is found). This hopefully will allow multicentered treatment protocols in the future.


Assuntos
Cerebelo/patologia , Cérebro/patologia , Progressão da Doença , Gastroenterite/complicações , Infecções Respiratórias/complicações , Convulsões Febris/diagnóstico , Estado Epiléptico/diagnóstico , Atrofia/patologia , Criança , Pré-Escolar , Feminino , Hipocampo/patologia , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Convulsões Febris/etiologia , Estado Epiléptico/etiologia , Síndrome
13.
Pediatr Neurol ; 61: 99-106, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27353696

RESUMO

BACKGROUND: Tics and Tourette syndrome are common problems evaluated by both the general pediatrician and pediatric neurologist. The common comorbidities of tics are well known, but the severe neurological complications are rare and may not be appreciated. METHODS: This is a retrospective case series and literature review. RESULTS: We present here four adolescents with Tourette syndrome who had severe neurological complications secondary to motor tics. We provide the history, neurological examination, and radiological findings in addition to a review of previously reported cases of vascular and cervical cord complications associated with violent motor tics. CONCLUSIONS: We highlight the importance of recognizing the presenting signs of these complications early and the need to vigorously treat violent motor tics to prevent significant neurological complications.


Assuntos
Síndrome de Tourette/complicações , Adolescente , Criança , Humanos , Masculino , Estudos Retrospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/terapia , Tiques/complicações , Tiques/diagnóstico por imagem , Tiques/terapia , Síndrome de Tourette/diagnóstico por imagem , Síndrome de Tourette/terapia
14.
mBio ; 6(6): e01863-15, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26670384

RESUMO

UNLABELLED: Avian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes--MYC, MYB, Mir-155, and TERT--have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high-throughput sequencing to identify additional genes driving tumorigenesis in ALV-induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, including TNFRSF1A, MEF2C, CTDSPL, TAB2, RUNX1, MLL5, CXorf57, and BACH2. We also analyze the genome-wide ALV integration landscape in vivo and find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integration in vivo in the chicken genome. IMPORTANCE: Avian leukosis virus induces B-cell lymphomas in chickens. Earlier studies showed that ALV can induce tumors through insertional mutagenesis, and several genes have been implicated in the development of these tumors. In this study, we use high-throughput sequencing to reveal the genome-wide ALV integration landscape in ALV-induced B-cell lymphomas. We find elevated levels of ALV integration near transcription start sites and use common integration site analysis to greatly expand the number of genes implicated in the development of these tumors. Interestingly, we identify several genes targeted by viral insertions that have not been previously shown to be involved in cancer.


Assuntos
Vírus da Leucose Aviária/fisiologia , Linfoma de Células B/virologia , Integração Viral , Animais , Galinhas , Sequenciamento de Nucleotídeos em Larga Escala , Sítio de Iniciação de Transcrição , Transcrição Gênica
15.
Genome Announc ; 3(2)2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25858851

RESUMO

We report the complete genome sequence of avian leukosis virus subgroup J (ALV-J) isolate PDRC-59831, which causes myeloid leukosis and hemangiomas in chickens. This is an American ALV-J isolate, which was found in a 38-week-old broiler breeder chicken on a farm in Georgia in 2007.

16.
Pediatr Neurol ; 53(3): 257-61, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26183178

RESUMO

BACKGROUND: Bupropion is a monocyclic antidepressant in the aminoketone class, structurally related to amphetamines. The Food and Drug Administration withdrew this product from the market in 1986 after seizures were reported in bulimic patients. It was later reintroduced in 1989 when the incidence of seizures was shown to be dose-related in the immediate release preparation. Massive bupropion ingestion has been associated with status epilepticus and cardiogenic shock in adults. Seizures have been reported in children, but not status epilepticus. This report highlights a patient who presented with status epilepticus and developed cardiopulmonary arrest after bupropion ingestion. False-positive amphetamine diagnosis from urine drug screen on presentation was reported. METHOD: We review the presentation, clinical course, diagnostic studies, and outcome of this patient. We then review the literature regarding bupropion overdose in children. RESULT: Symptoms of bupropion toxicity and risk for seizures are dose-dependent and fatalities have been reported. Our patient developed status epilepticus and cardiopulmonary arrest and then progressed to have a hypoxic ischemic encephalopathy and refractory symptomatic partial seizures. CONCLUSION: Our report highlights the need to keep this medication away from children in order to prevent accidental overdose.


Assuntos
Antidepressivos de Segunda Geração/toxicidade , Bupropiona/toxicidade , Overdose de Drogas/diagnóstico , Estado Epiléptico/diagnóstico , Encéfalo/patologia , Diagnóstico Diferencial , Overdose de Drogas/patologia , Overdose de Drogas/fisiopatologia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Estado Epiléptico/patologia , Estado Epiléptico/fisiopatologia
17.
J Child Neurol ; 29(4): 555-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23481445

RESUMO

Baclofen is a γ-aminobutyric acid (GABA) agonist that is commonly prescribed for the treatment of spasticity in children. The clinical indications for baclofen use in the pediatric population have increased in recent years. Prescribing baclofen mandates education regarding abrupt withdrawal and overdose because of the severe clinical reactions this can precipitate. This report highlights the case of a patient who presented with acute onset of coma and a flaccid paralysis after baclofen overdose. We reviewed the presentation, clinical course, diagnostic studies, and outcome of this patient. A review of prior literature regarding baclofen overdose is included. Baclofen overdose is heralded by dose-related alteration in consciousness and weakness, progressing to coma and a flaccid paralysis. Screening for baclofen overdose is accomplished through high-power liquid chromatography. Baclofen overdose is treated with supportive care and antiepileptic medications as indicated. There is usually full spontaneous recovery with elimination of the medication.


Assuntos
Baclofeno/efeitos adversos , Coma/induzido quimicamente , Overdose de Drogas/etiologia , Relaxantes Musculares Centrais/efeitos adversos , Quadriplegia/induzido quimicamente , Adolescente , Sistema Nervoso Central/patologia , Overdose de Drogas/complicações , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética
18.
J Child Neurol ; 29(2): 162-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23392562

RESUMO

Time to treatment of seizures is critical to efficacy. We performed a quality initiative and evaluated time to treatment of inpatient seizure emergencies with first- and second-line medicines before and after implementation of a computerized, standard treatment protocol. Data from 125 patients revealed that 179 seizure episodes required first-line antiepileptic drugs, and the mean time to treatment was 7.72 minutes. In 87 episodes, patients (49%) received the drugs within 5 minutes. Forty-six episodes required second-line drugs. In 17 (37%), patients received them within 30 minutes (mean 49.48 minutes). After implementation of the protocol, the mean time to treatment with first-line drugs was 3.74 minutes, a reduction of >50% (P < .0001). The mean time to treatment with second-line drugs was 25.05 minutes, a reduction of ∼50% (P < .0001). This effective model for reducing the time to treatment of seizure emergencies may be useful to similar institutions.


Assuntos
Protocolos Clínicos , Quimioterapia Assistida por Computador/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Convulsões/tratamento farmacológico , Tempo para o Tratamento , Anticonvulsivantes/uso terapêutico , Criança , Hospitais Pediátricos/normas , Humanos , Neurologia/normas , Estado Epiléptico/tratamento farmacológico
19.
BMC Proc ; 5 Suppl 4: S2, 2011 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-21645299

RESUMO

BACKGROUND: MicroRNAs are short RNAs (~22 nt) expressed by plants, animals and viruses that regulate gene expression post-transcriptionally, and their importance is highlighted by distinct patterns of expression in many physiological processes, including development, hematopoeisis, stress resistance, and disease. Our group has characterized the microRNAs encoded by the avian herpesviruses; namely, oncogenic Marek's disease (MD) virus (MDV1), non-oncogenic MDV (MDV2) herpesvirus of turkeys (HVT), and infectious laryngotracheitis virus (ILTV). METHODS: MicroRNAs encoded by the avian herpesviruses were identified using next generation sequencing technologies (454, Illumina). RESULTS: The microRNAs of each the avian herpesviruses have unique sequences, but the genomic locations are similar, in that the microRNAs tend to be clustered in the rapidly evolving repeat regions of the viral genomes. For a given viral species the microRNA sequence is highly conserved in different strains with the exception of a virulence-associated polymorphism in the putative promoter of the MDV1 microRNAs upstream of the meq oncogene. These microRNAs are relatively highly expressed in tumors produced by very virulent MDV1 isolates compared to tumors produced by less virulent strains. MDV1 and HVT encode homologs of the host microRNA, miR-221, which targets a gene important in cell cycle regulation. MDV1 encodes a microRNA (mdv1-miR-M4) that shares a seed sequence with miR-155, a microRNA important in immune function. Mdv-miR-M4 is highly expressed in MDV induced tumors, while miR-155 is present at very low levels. CONCLUSIONS: MicroRNAs are highly conserved among different field strains of MDV1, and they are expressed in lytic and latent infections and in MDV1-derived tumors. This suggests that these small molecules are very important to the virus, and roles in immune evasion, anti-apoptosis, or proliferation are likely.

20.
PLoS One ; 6(9): e24785, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21949751

RESUMO

Viral and bacterial pathogens are a significant economic concern to the US broiler industry and the ecological epicenter for poultry pathogens is the mixture of bedding material, chicken excrement and feathers that comprises the litter of a poultry house. This study used high-throughput sequencing to assess the richness and diversity of poultry litter bacterial communities, and to look for connections between these communities and the environmental characteristics of a poultry house including its history of gangrenous dermatitis (GD). Cluster analysis of 16S rRNA gene sequences revealed differences in the distribution of bacterial phylotypes between Wet and Dry litter samples and between houses. Wet litter contained greater diversity with 90% of total bacterial abundance occurring within the top 214 OTU clusters. In contrast, only 50 clusters accounted for 90% of Dry litter bacterial abundance. The sixth largest OTU cluster across all samples classified as an Arcobacter sp., an emerging human pathogen, occurring in only the Wet litter samples of a house with a modern evaporative cooling system. Ironically, the primary pathogenic clostridial and staphylococcal species associated with GD were not found in any house; however, there were thirteen 16S rRNA gene phylotypes of mostly gram-positive phyla that were unique to GD-affected houses and primarily occurred in Wet litter samples. Overall, the poultry house environment appeared to substantially impact the composition of litter bacterial communities and may play a key role in the emergence of food-borne pathogens.


Assuntos
Bactérias/genética , Abrigo para Animais , Esterco/microbiologia , Aves Domésticas , Animais , Bactérias/classificação , Análise por Conglomerados , Dermatite/microbiologia , Biblioteca Gênica , Genes Bacterianos/genética , Variação Genética , Humanos , RNA Ribossômico 16S/genética
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