RESUMO
Shiga toxin-producing Escherichia coli (STEC) are important enteric pathogens responsible for sporadic cases and outbreaks of gastroenteritis. E.coli O157:H7/NM (STEC O157) are the most commonly known STEC serotypes but it is now increasingly apparent that non-O157 STEC serotypes have been underreported in the past because they were not part of routine screening in many front-line laboratories. The Canadian Public Health Laboratory Network (CPHLN) has identified the need for improved detection and surveillance of non-O157 STEC and has developed the following recommendations to assist in the decision-making process for clinical and reference microbiology laboratories. These recommendations should be followed to the best of a laboratory's abilities based on the availability of technology and resources. The CPHLN recommends that when screening for the agents of bacterial gastroenteritis from a stool sample, front-line laboratories use either a chromogenic agar culture or a culture-independent diagnostic test (CIDT). CIDT options include nucleic acid amplification tests (NAATs) to detect Shiga toxin genes or enzyme immunoassays (EIAs) to detect Shiga toxins. If either CIDT method is positive for possible STEC, laboratories must have a mechanism to culture and isolate STEC in order to support both provincial and national surveillance as well as outbreak investigations and response. These CPHLN recommendations should result in improved detection of STEC in patients presenting with diarrhea, especially when due to the non-O157 serotypes. These measures should enhance the overall quality of healthcare and food safety, and provide better protection of the public via improved surveillance and outbreak detection and response.
RESUMO
OBJECTIVE: Indicators for head CT scan defined by the 2007 National Institute for Health and Care Excellence (NICE) guidelines were analysed to identify CT uptake, influential variables and yield. DESIGN: Cross-sectional study. SETTING: Hospital inpatient units: England, Wales, Northern Ireland and the Channel Islands. PATIENTS: Children (<15â years) admitted to hospital for more than 4â h following a head injury (September 2009 to February 2010). INTERVENTIONS: CT scan. MAIN OUTCOME MEASURES: Number of children who had CT, extent to which NICE guidelines were followed and diagnostic yield. RESULTS: Data on 5700 children were returned by 90% of eligible hospitals, 84% of whom were admitted to a general hospital. CT scans were performed on 30.4% of children (1734), with a higher diagnostic yield in infants (56.5% (144/255)) than children aged 1 to 14â years (26.5% (391/1476)). Overall, only 40.4% (984 of 2437 children) fulfilling at least one of the four NICE criteria for CT actually underwent one. These children were much less likely to receive CT if admitted to a general hospital than to a specialist centre (OR 0.52 (95% CI 0.45 to 0.59)); there was considerable variation between healthcare regions. When indicated, children >3â years were much more likely to have CT than those <3â years (OR 2.35 (95% CI 2.08 to 2.65)). CONCLUSION: Compliance with guidelines and diagnostic yield was variable across age groups, the type of hospital and region where children were admitted. With this pattern of clinical practice the risks of both missing intracranial injury and overuse of CT are considerable.
Assuntos
Traumatismos Craniocerebrais/diagnóstico por imagem , Seleção de Pacientes , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Acidentes por Quedas/estatística & dados numéricos , Acidentes Domésticos , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Procedimentos Clínicos , Estudos Transversais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Prevalência , Fraturas Cranianas/diagnóstico por imagem , Fraturas Cranianas/epidemiologia , Tempo para o Tratamento , Resultado do Tratamento , Inconsciência/diagnóstico por imagem , Inconsciência/epidemiologia , Reino Unido/epidemiologia , Procedimentos Desnecessários/estatística & dados numéricosRESUMO
Staphylococcus aureus bacteraemia (SAB) is a common, serious infection that is associated with high rates of morbidity and mortality. Evidence suggests that infectious disease consultation (IDC) improves clinical management in patients with SAB. We examined whether the introduction of a routine bedside IDC service for adults with SAB improved clinical management and outcomes compared to telephone consultation. We conducted an observational cohort study of 571 adults with SAB at a teaching hospital in the United Kingdom between July 2006 and December 2012. A telephone consultation was provided on the day of positive blood culture in all cases, but an additional bedside IDC was provided after November 2009 (routine IDC group). Compared to patients in the pre-IDC group, those in the routine IDC group were more likely to have a removable focus of infection identified, echocardiography performed and follow-up blood cultures performed. They also received longer courses of antimicrobial therapy, were more likely to receive combination antimicrobial therapy and were more likely to have SAB recorded in the hospital discharge summary. There was a trend towards lower mortality at 30 days in the routine IDC group compared to the pre-IDC group (12% vs. 22%, p 0.07). Our findings suggest that routine bedside IDC should become the standard of care for adults with SAB.
Assuntos
Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Encaminhamento e Consulta/estatística & dados numéricos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Estudos de Coortes , Feminino , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Estafilocócicas/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
Williams syndrome (WS) is a neurodevelopmental disorder with a variable phenotype. Molecular genetic studies have indicated that hemizygosity at the elastin locus (ELN) may account for the cardiac abnormalities seen in WS, but that mental retardation and hypercalcemia are likely caused by other genes flanking ELN. In this study, we defined the minimal critical deletion region in 63 patients using 10 microsatellite markers and 5 fluorescence in situ hybridization (FISH) probes on chromosome 7q, flanking ELN. The haplotype analyses showed the deleted cases to have deletions of consistent size, as did the FISH analyses using genomic probes for the known ends of the commonly deleted region defined by the satellite markers. In all informative cases deleted at ELN, the deletion extends from D7S489U to D7S1870. The genetic distance between these two markers is about 2 cM. Of the 51 informative patients with deletions, 29 were maternal and 22 were paternal in origin. There was no evidence for effects on stature by examining gender, ethnicity, cardiac status, or parental origin of the deletion. Heteroduplex analysis for LIMK1, a candidate gene previously implicated in the WS phenotype, did not show any mutations in our WS patients not deleted for ELN. LIMK1 deletions were found in all elastin-deletion cases who had WS. One case, who has isolated, supravalvular aortic stenosis and an elastin deletion, was not deleted for LIMK1. It remains to be determined if haploinsufficiency of LIMK1 is responsible in part for the WS phenotype or is simply deleted due to its close proximity to the elastin locus.
Assuntos
Cromossomos Humanos Par 7 , Elastina/genética , Transtornos do Crescimento/genética , Cardiopatias Congênitas/genética , Síndrome de Williams/genética , DNA/análise , Análise Mutacional de DNA , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Deleção de Sequência , Síndrome de Williams/etnologia , Síndrome de Williams/fisiopatologiaRESUMO
Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer.
Assuntos
RNA Helicases DEAD-box/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Mutação , Blastoma Pulmonar/genética , Ribonuclease III/genética , Proteína Supressora de Tumor p53/genética , Sequência de Bases , Cromossomos Humanos Par 5/genética , RNA Helicases DEAD-box/metabolismo , Variações do Número de Cópias de DNA , Exoma/genética , Feminino , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/química , Conformação de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Blastoma Pulmonar/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribonuclease III/metabolismo , Análise de Sequência de DNA/métodos , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Clostridium difficile infection remains a major challenge for hospitals. Although targeted infection control initiatives have been shown to be effective in reducing the incidence of hospital-acquired C. difficile infection, there is little evidence available to assess the effectiveness of specific interventions. AIM: To use statistical modelling to detect substantial reductions in the incidence of C. difficile from time series data from two hospitals in England, and relate these time points to infection control interventions. METHODS: A statistical breakpoints model was fitted to likely hospital-acquired C. difficile infection incidence data from a teaching hospital (2002-2009) and a district general hospital (2005-2009) in England. Models with increasing complexity (i.e. increasing the number of breakpoints) were tested for an improved fit to the data. Partitions estimated from breakpoint models were tested for individual stability using statistical process control charts. Major infection control interventions from both hospitals during this time were grouped according to their primary target (antibiotics, cleaning, isolation, other) and mapped to the model-suggested breakpoints. FINDINGS: For both hospitals, breakpoints coincided with enhancements to cleaning protocols. Statistical models enabled formal assessment of the impact of different interventions, and showed that enhancements to deep cleaning programmes are the interventions that have most likely led to substantial reductions in hospital-acquired C. difficile infections at the two hospitals studied.
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Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/prevenção & controle , Infecção Hospitalar/prevenção & controle , Desinfecção/métodos , Zeladoria Hospitalar/métodos , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Inglaterra , Pesquisa sobre Serviços de Saúde/métodos , Hospitais , Humanos , Modelos EstatísticosAssuntos
Adaptação Psicológica , Paraplegia/reabilitação , Escolaridade , Fantasia , Humanos , Masculino , Motivação , Ocupações , Personalidade , Ajustamento Social , Classe Social , Fatores SocioeconômicosRESUMO
The complete sequencing of the human genome and the development of molecularly targeted cancer therapy have promoted efforts to identify systematically the genetic alterations in human cancer. By high-throughput sequencing of tyrosine kinase genes in human non-small-cell lung cancer, we identified somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene (EGFR) that are correlated with clinical response to EGFR tyrosine kinase inhibitors (TKIs). We have shown that these mutant forms of EGFR induce oncogenic transformation in different cellular systems. Cells whose growth depends on EGFR with mutations in exons 19 and 21 are sensitive to EGFR-TKIs, whereas cells expressing insertion mutations in exon 20 or the T790M point mutant, found in tumor biopsies from patients that relapsed after an initial response to EGFR-TKIs, are resistant. Furthermore, by applying a novel, massively parallel sequencing technology, we have shown that clinically relevant oncogene mutations can be detected in clinical specimens with very low tumor content, thereby enabling optimal patient selection for mutation-directed therapy. In summary, by applying high-throughput genomic resequencing, we have identified a novel therapeutic target, mutant EGFR, in lung cancer and evaluated its role in predicting response to targeted therapy.
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Adenocarcinoma/genética , Genes erbB-1 , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/enzimologia , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/química , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Camundongos , Células NIH 3T3 , Inibidores de Proteínas Quinases/uso terapêutico , Estrutura Terciária de ProteínaRESUMO
The Edwards Personal Preference Schedule (EPPS) was administered to 24 outstanding U.S. female athletes who were competitors in the 1972 Olympic Games. The resulting EPPS group profile strongly points to the essential normality of these competitors. Within the framework of a well-balanced needs profile, the two highest group needs scores were in the realm of achievement and autonomy. Thus, these prominent athletes demonstrated the kind of personality profile anticipated from a group of women with seemingly high needs for achievement and self-accomplishment. The EPPS, therefore, appears to be a promising personality measure to assess achievement motivation.
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Impulso (Psicologia) , Personalidade , Esportes , Logro , Agressão , Atenção , Feminino , Humanos , Individualidade , Entrevista Psicológica , Motivação , Inventário de Personalidade , Autoimagem , Inquéritos e Questionários , Estados UnidosRESUMO
High-resolution G-banding analysis has demonstrated remarkable morphological conservation of the chromosomes of the Hominidae family members (humans, chimpanzees, gorillas, and orangutans), with the most notable differences between the genomes appearing as changes in heterochromatin distribution and pericentric inversions. Pericentric inversions may have been important for the establishment of reproductive isolation and speciation of the hominoids as they diverged from a common ancestor. Here the previously published primate karyotype comparisons, coupled with the resources of the Human Genome Project, have been used to identify pericentric inversion breakpoints seen when comparing the human karyotype to that of chimpanzee. Yeast artificial chromosome (YAC) clones were used to detect, by fluorescence in situ hybridization, five evolutionary pericentric inversion breakpoints present on the chimpanzee chromosome equivalents of human chromosomes 4, 9, and 12. In addition, two YACs from human 12p that detect a breakpoint in chimpanzee detect a similar rearrangement in gorilla.
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Inversão Cromossômica , Mapeamento Cromossômico , Evolução Molecular , Hominidae/genética , Pan troglodytes/genética , Animais , Bandeamento Cromossômico , Quebra Cromossômica , Cromossomos Artificiais de Levedura , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 9 , Gorilla gorilla/genética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Pongo pygmaeus/genéticaRESUMO
To investigate the frequency of deletions of the elastin gene in patients with Williams syndrome (WS), we screened 44 patients by both FISH and PCR amplification of a dinucleotide repeat polymorphism. FISH was performed using cosmids containing either the 5' or the 3' end of the elastin gene. PCR analysis was performed on the patients and their parents with a (CA)n repeat polymorphism found in intron 17 of the elastin locus. Of the 44 patients screened, 91% were shown to be deleted by FISH. Using the DNA polymorphism, both maternally (39%) and paternally (61%) derived deletions were found. Four patients were not deleted for elastin but have clinical features of WS. Since deletions of elastin cannot account for several features found in WS, these patients will be valuable in further delineation of the critical region responsible for the WS phenotype. Although PCR can be useful for determining the parental origin of the deletion, our results demonstrate that FISH analysis of the elastin locus provides a more rapid and informative test to confirm a clinical diagnosis of WS. The presence of two copies of the elastin locus in a patient does not, however, rule out WS as a diagnosis.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 7/genética , Elastina/genética , Deleção de Genes , Anormalidades Múltiplas/diagnóstico , Estenose da Valva Aórtica/genética , Face/anormalidades , Feminino , Transtornos do Crescimento/genética , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Cariotipagem , Masculino , Reação em Cadeia da PolimeraseRESUMO
With the ultimate goal of creating a sequence-ready physical map of all of chromosome 5, 303 new human chromosome 5-specific STS markers have been systematically generated and regionally ordered. Chromosome 5 DNA prepared from flow-sorted chromosomes was digested with restriction enzymes BamHI and HindIII and cloned in bacteriophage M13mp18. Random clones were sequenced, and appropriate PCR deoxyoligomers were synthesized. An acceptable sequence-tagged site (STS)-PCR assay yielded the appropriate size amplification product from both total human DNA and hybrid cell line DNA containing only human chromosome 5. Each STS has been regionally localized by breakpoint analysis using a set of hybrid cell panels consisting of natural deletions or translocations of human chromosome 5. This hybrid cell panel was able to localize the STSs to 1 of 51 bins on the short arm and 1 of 15 bins on the long arm. The STS markers appear to be randomly distributed along the length of this 194-Mb chromosome. The current overall density of these markers (approximately 1 STS/640 kb), combined with the numerous PCR-based physical and genetic markers generated by other groups, will provide sufficient "nucleation points" for YAC contig assembly and verification in any region of human chromosome 5.
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Mapeamento Cromossômico , Cromossomos Humanos Par 5/genética , Sitios de Sequências Rotuladas , Animais , Bandeamento Cromossômico , Cromossomos Artificiais de Levedura/genética , Cromossomos Humanos Par 5/ultraestrutura , Clonagem Molecular , Cricetinae , Marcadores Genéticos , Humanos , Células Híbridas , Reação em Cadeia da PolimeraseRESUMO
Sialic acids are important cell-surface molecules of animals in the deuterostome lineage. Although humans do not express easily detectable amounts of N-glycolylneuraminic acid (Neu5Gc, a hydroxylated form of the common sialic acid N-acetylneuraminic acid, Neu5Ac), it is a major component in great ape tissues, except in the brain. This difference correlates with lack of the hydroxylase activity that converts CMP-Neu5Ac to CMP-Neu5Gc. Here we report cloning of human and chimpanzee hydroxylase cDNAs. Although this chimpanzee cDNA is similar to the murine homologue, the human cDNA contains a 92-bp deletion resulting in a frameshift mutation. The isolated human gene also shows evidence for this deletion. Genomic PCR analysis indicates that this deletion does not occur in any of the African great apes. The gene is localized to 6p22-p23 in both humans and great apes, which does not correspond to known chromosomal rearrangements that occurred during hominoid evolution. Thus, the lineage leading to modern humans suffered a mutation sometime after the common ancestor with the chimpanzee and bonobo, potentially affecting recognition by a variety of endogenous and exogenous sialic acid-binding lectins. Also, the expression of Neu5Gc previously reported in human fetuses and tumors as well as the traces detected in some normal adult humans must be mediated by an alternate pathway.