RESUMO
OBJECTIVE: The objective of the study is to determine if tamsulosin initiated in the emergency department (ED) decreases the time to ureteral stone passage at 1 week or time to pain resolution, compared to placebo. METHODS: We performed a prospective, randomized, double-blinded, placebo-controlled trial of tamsulosin vs placebo in ED patients with ureterolithiasis on computed tomography. Patients were identified and enrolled between April 2007 and February 2009 and were randomized to either 0.4 mg of tamsulosin or placebo for 1 week. We contacted participants using a telephone survey on post-ED visit days 1, 2, 3, and 7. The primary outcome was time to stone passage, with secondary outcomes being maximum pain score and amount of pain medication required. RESULTS: Of the 127 patients enrolled during this study, 15 were lost to follow-up, and 12 required surgical interventions before the 7-day mark, leaving 100 patients for analysis. Of the 100 patients, 53 received tamsulosin and 47 received placebo. There was no difference between groups in percentage of male, mean age, initial serum creatinine, average stone size, stone location, and history of prior stone. The probability that the patient did not pass a stone at 7 days was not different between tamsulosin and placebo, 62.1% (95% confidence interval, 49.1%-75.1%) vs 54.4% (95% confidence interval, 40.3%-68.6%; P = .58). There was no significant difference in the high pain score (P = .12) or hydrocodone/acetaminophen intake (P = .76) between treatment groups at any of the time points. CONCLUSION: This study reveals no difference in the proportion of stone passage or high pain score and pain medication utilization at 7 days between tamsulosin and placebo.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Serviço Hospitalar de Emergência , Sulfonamidas/uso terapêutico , Cálculos Ureterais/tratamento farmacológico , Adulto , Analgésicos/uso terapêutico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Dor/etiologia , Dor/prevenção & controle , Estudos Prospectivos , Tansulosina , Fatores de Tempo , Resultado do Tratamento , Cálculos Ureterais/complicações , Cálculos Ureterais/diagnósticoRESUMO
Vitamins A and E are fat-soluble vitamins that play important roles in several physiological processes. Monitoring their concentrations is needed to detect deficiency and guide therapy. In this study, we developed a high-performance liquid chromatography method to measure the major forms of vitamin A (retinol) and vitamin E (α-tocopherol and γ-tocopherol) in human blood plasma. Vitamins A and E were extracted with hexane and separated on a reversed-phase column using methanol as the mobile phase. Retinol was detected by ultraviolet absorption, whereas tocopherols were detected by fluorescence emission. The chromatographic cycle time was 4.0 min per sample. The analytical measurement range was 0.03-5.14, 0.32-36.02, and 0.10-9.99 mg/L for retinol, α-tocopherol, and γ-tocopherol, respectively. Intr-aassay and total coefficient of variation were <6.0% for all compounds. This method was traceable to standard reference materials offered by the National Institute of Standards and Technology. Reference intervals were established using plasma samples collected from 51 healthy adult donors and were found to be 0.30-1.20, 6.0-23.0, and 0.3-3.2 mg/L for retinol, α-tocopherol, and γ-tocopherol, respectively. In conclusion, we developed and validated a fast, simple, and sensitive high-performance liquid chromatography method for measuring the major forms of vitamins A and E in human plasma.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Vitamina A/sangue , Vitamina E/sangue , Humanos , Sensibilidade e EspecificidadeRESUMO
In the oleaginous yeast Yarrowia lipolytica, de novo lipid synthesis and accumulation are induced under conditions of nitrogen limitation (or a high carbon-to-nitrogen ratio). The regulatory pathway responsible for this induction has not been identified. Here we report that the SNF1 pathway plays a key role in the transition from the growth phase to the oleaginous phase in Y. lipolytica. Strains with a Y. lipolytica snf1 (Ylsnf1) deletion accumulated fatty acids constitutively at levels up to 2.6-fold higher than those of the wild type. When introduced into a Y. lipolytica strain engineered to produce omega-3 eicosapentaenoic acid (EPA), Ylsnf1 deletion led to a 52% increase in EPA titers (7.6% of dry cell weight) over the control. Other components of the Y. lipolytica SNF1 pathway were also identified, and their function in limiting fatty acid accumulation is suggested by gene deletion analyses. Deletion of the gene encoding YlSnf4, YlGal83, or YlSak1 significantly increased lipid accumulation in both growth and oleaginous phases compared to the wild type. Furthermore, microarray and quantitative reverse transcription-PCR (qRT-PCR) analyses of the Ylsnf1 mutant identified significantly differentially expressed genes during de novo lipid synthesis and accumulation in Y. lipolytica. Gene ontology analysis found that these genes were highly enriched with genes involved in lipid metabolism. This work presents a new role for Snf1/AMP-activated protein kinase (AMPK) pathways in lipid accumulation in this oleaginous yeast.
Assuntos
Regulação Fúngica da Expressão Gênica , Metabolismo dos Lipídeos , Proteínas Serina-Treonina Quinases/metabolismo , Yarrowia/genética , Yarrowia/metabolismo , Deleção de Genes , Perfilação da Expressão Gênica , Análise em Microsséries , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase em Tempo Real , Yarrowia/enzimologiaRESUMO
Oleaginous yeast Yarrowia lipolytica is an important host for the production of lipid-derived compounds or heterologous proteins. Selection of strong promoters and effective expression systems is critical for heterologous protein secretion. To search for a strong promoter in Y. lipolytica, activities of FBA1, TDH1 and GPM1 promoters were compared to that of TEF1 promoter by constructing GUS reporter fusions. The FBA1 promoter activity was 2.2 and 5.5 times stronger than the TDH1 and GPM1 promoters, respectively. The FBA1IN promoter (FBA1 sequence of -826 to +169) containing an intron (+64 to +165) showed five-fold higher expression than the FBA1 promoter (-831 to -1). The transcriptional enhancement by the 5'-region within the FBA1 gene was confirmed by GPM1::FBA1 chimeric promoter construction. Using the strong FBA1IN promoter, four different S. cerevisiae SUC2 expression cassettes were tested for the SUC+ phenotype in Y. lipolytica. Functional invertase secretion was facilitated by the Xpr2 prepro-region with an additional 13 amino acids of mature Xpr2, or by the native Suc2 signal sequence. However, these two secretory signals in tandem, or the mature Suc2 with no secretory signal, did not direct secretion of functional invertase. Unlike previously reported Y. lipolytica SUC+ strains, our engineered stains secreted most of invertase into the medium.
Assuntos
Regiões Promotoras Genéticas/genética , Yarrowia/genética , beta-Frutofuranosidase/metabolismo , Sequência de Bases , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes Reporter , Engenharia Genética , Vetores Genéticos/genética , Dados de Sequência Molecular , Fenótipo , Sacarose/metabolismo , Yarrowia/enzimologia , beta-Frutofuranosidase/genéticaRESUMO
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an established biomarker for endothelial function, while symmetric dimethylarginine (SDMA), an emerging biomarker for renal function, has been shown to outperform creatinine-based equations for estimated glomerular filtration rate. In order to study these analytes for clinical research, a fast and simple method for measuring arginine (ARG), SDMA, and ADMA in plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed. Plasma (50 µL) was mixed with 50 µL of internal standard of (13)C-arginine and d(7)-ADMA followed by protein precipitation with methanol containing 1% ammonium acetate (300 µL). After centrifugation, the supernatant (100 µL) was mixed with 300 µL of acetonitrile with 1% formic acid, and the mixture was injected onto a silica column monitored by a mass spectrometer. The analytical cycle time was 5.0 min. The method was linear from 5.7 to 489.7 µM for ARG, 0.06 to 5.15 µM for SDMA, and from 0.34 to 5.65 µM for ADMA, with an accuracy of 99.0-120.0%. Total coefficients of variation for all analytes ranged from 2.7% to 7.7% for three concentration levels. The effects of hemolysis, lipemia, uremia, icterus, specimen tube types, storage at different temperature, and freeze/thaw were thoroughly investigated. Reference ranges were established using 51 well-defined reference subjects (12 men and 39 women, age 19-64 years): 53.1-129.7 µM for ARG, 0.32-0.65 µM for SDMA, and 0.36-0.67 µM for ADMA. In conclusion, the validated LC-MS/MS method described here offers a fast and reliable ARG, SDMA, and ADMA quantitation in plasma with minimum sample preparation.
Assuntos
Arginina/análogos & derivados , Arginina/sangue , Técnicas de Laboratório Clínico , Adulto , Cromatografia Líquida de Alta Pressão/normas , Técnicas de Laboratório Clínico/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Espectrometria de Massas em Tandem/normas , Adulto JovemRESUMO
UNLABELLED: There is a developing body of literature documenting adverse survival outcome of out-of-hospital endotracheal intubation for critical multiple trauma and head injury patients. OBJECTIVE: To compare the rates of survival to hospital admission and discharge of nontraumatic out-of-hospital cardiac arrest (OHCA) patients who received successful out-of-hospital endotracheal intubation and those who were not intubated. METHODS: We conducted a retrospective analysis from an ongoing database of OHCA patients brought to a large suburban tertiary care emergency department by paramedic services between 1995 and 2006. We dichotomized patients by whether they were successfully endotracheally intubated or not prior to hospital arrival. Utstein style cardiac arrest variables were abstracted for all cases. All survivors to hospital admission were reviewed to exclude those patients in whom intubation was not attempted or unnecessary, such as those who had successful first-shock recovery of spontaneous circulation. We used chi square and logistic regression techniques for analysis, using survival to discharge as the primary outcome and survival to admission as a secondary outcome. RESULTS: There were 1,515 total cases with 33 early survivors excluded. Overall, 1,220 (86.2%) were intubated; of those intubated, 270 (20.2%) survived to admission and 93 (7.0%) survived to discharge. Upon univariate analysis, there was no difference in survival between intubated and non intubated groups (6.5% vs 10.0%, OR = 0.63, 95% CI 0.37,1.08). For patients initially in ventricular fibrillation/ventricular tachycardia (VT/VF), in a multivariate Logit model, intubation significantly decreased survival to discharge, adjusted odds ratio (OR) = 0.52 (95% confidence interval 0.27, 0.998). Intubated non-VF patients were more likely to survive to admission, adjusted OR 2.96 (1.04, 8.43), but not to discharge (1.8% vs. 1.0%, p = 1.0). CONCLUSION: This observational study in an unselected population shows that patients in VF/VT arrest who underwent out-of-hospital intubation were less likely to survive to discharge than those not intubated. Out-of-hospital intubation of patients with non-VF arrest was associated with an increased rate of survival to admission, but not survival to discharge. Future prospective studies are needed to define the role of out-of-hospital endotracheal intubation in cardiac arrest patients.
Assuntos
Serviços Médicos de Emergência/métodos , Intubação Intratraqueal/mortalidade , Suporte Vital Cardíaco Avançado , Idoso , Idoso de 80 Anos ou mais , Manuseio das Vias Aéreas/métodos , Intervalos de Confiança , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Intubação Intratraqueal/métodos , Intubação Intratraqueal/estatística & dados numéricos , Modelos Logísticos , Masculino , Michigan , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Análise de Regressão , Estudos Retrospectivos , Análise de Sobrevida , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/terapia , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/terapiaRESUMO
Introduction Insufficient attention has been directed towards urosepsis. Notably, no protocols or clinical decision rules currently exist outlining the appropriate use of imaging in uroseptic patients. The primary objective of our study was to retrospectively evaluate uroseptic emergency department (ED) patients who underwent abdominal imaging, to report the proportion of patients with imaging findings necessitating emergent surgical consultation. Methods We retrospectively identified 1142 patients ≥ 18 years of age that presented to the ED from January 2009 to December 2012 with ICD9 code indicative of urosepsis. All included patients underwent ED-ordered abdominal computerized tomography (CT) or retroperitoneal ultrasound (US). Imaging and urinalysis (UA) results were categorized. We report proportions with odds ratios and 95% confidence intervals. Results Of 1142 patients, we excluded 80 for neg UA, 167 for < 2 SIRS (systemic inflammatory response syndrome), 320 for positive blood cultures, and 37 for incomplete data. This yielded 538 patients which the authors reviewed the results of the CT or US to determine the proportion who required emergent surgical consultation and who underwent surgical or interventional procedure. There were 243 (45%) that had CT or US results that necessitated emergency surgical consultation, of those 180 (33%) underwent surgical or interventional procedure. Similar rates of emergency surgical consultation occurred when sub-divided by positive versus equivocal UA, with 43% and 47%, respectively. Conclusions Forty-five percent of our abdominally imaged urosepsis cohort had imaging findings that necessitated emergent surgical consultation, with a similar proportion in the subset with positive versus equivocal UA. The utility of abdominal imaging in this population should be studied prospectively.
RESUMO
Importance: Outdoor particulate matter 2.5 µm or less in diameter (PM2.5) is a ubiquitous environmental neurotoxicant that may affect the developing brain. Little is known about associations between PM2.5 and white matter connectivity. Objectives: To assess associations between annual residential PM2.5 exposure and white matter microstructure health in a US sample of children 9 to 10 years of age and to examine whether associations are specific to certain white matter pathways or vary across neuroimaging diffusion markers reflective of intracellular and extracellular microstructural processes. Design, Setting, and Participants: This cross-sectional study, the Adolescent Brain and Cognitive Development (ABCD) Study, was composed of 21 study sites across the US and used baseline data collected from children 9 to 10 years of age from September 1, 2016, to October 15, 2018. Data analysis was performed from September 15, 2020, to June 30, 2021. Exposures: Annual mean PM2.5 exposure estimated by ensemble-based models and assigned to the primary residential addresses at baseline. Main Outcomes and Measures: Diffusion-weighted imaging (DWI) and tractography were used to delineate white matter tracts. The biophysical modeling technique of restriction spectrum imaging (RSI) was implemented to examine total hindered diffusion and restricted isotropic and anisotropic intracellular diffusion in each tract. Hierarchical mixed-effects models with natural splines were used to analyze the associations between PM2.5 exposure and DWI. Results: In a study population of 7602 children (mean [SD] age, 119.1 [7.42] months; 3955 [52.0%] female; 160 [ 21.%] Asian, 1025 [13.5%] Black, 1616 [21.3%] Hispanic, 4025 [52.9%] White, and 774 [10.2%] other [identified by parents as American Indian/Native American or Alaska Native; Native Hawaiian, Guamanian, Samoan, other Pacific Islander; Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, or other Asian; or other race]), associations were seen between annual ambient PM2.5 and hemispheric differences in white matter microstructure. Hemisphere-stratified models revealed significant associations between PM2.5 exposure and restricted isotropic intracellular diffusion in the left cingulum, in the left superior longitudinal fasciculus, and bilaterally in the fornix and uncinate fasciculus. In tracts with strong positive associations, a PM2.5 increase from 8 to 12 µg/m3 was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Widespread negative associations were observed between PM2.5 and mean diffusivity. Conclusions and Relevance: The findings of this cross-sectional study suggest that annual mean PM2.5 exposure during childhood is associated with increased restricted isotropic diffusion and decreased mean diffusivity of specific white matter tracts, potentially reflecting differences in the composition of white matter microarchitecture.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Desenvolvimento Infantil/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Neurotoxinas/efeitos adversos , Material Particulado/efeitos adversos , Substância Branca/anatomia & histologia , Substância Branca/efeitos dos fármacos , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Estados UnidosRESUMO
BACKGROUND: Trichoderma reesei is one of the best-known cellulolytic organisms, producing large quantities of a complete set of extracellular cellulases and hemicellulases for the degradation of lignocellulosic substances. Hence, T. reesei is a biotechnically important host and it is used commercially in enzyme production, of both native and foreign origin. Many strategies for producing enzymes in T. reesei rely on the cbh1 and other cellulase gene promoters for high-level expression and these promoters require induction by sophorose, lactose or other inducers for high productivity during manufacturing. RESULTS: We described an approach for producing high levels of secreted proteins by overexpression of a transcription factor ACE3 in T. reesei. We refined the ace3 gene structure and identified specific ACE3 variants that enable production of secreted cellulases and hemicellulases on glucose as a sole carbon source (i.e., in the absence of an inducer). These specific ACE3 variants contain a full-length Zn2Cys6 binuclear cluster domain at the N-terminus and a defined length of truncations at the C-terminus. When expressed at a moderate level in the fungal cells, the ACE3 variants can induce high-level expression of cellulases and hemicellulases on glucose (i.e., in the absence of an inducer), and further improve expression on lactose or glucose/sophorose (i.e., in the presence of an inducer). Finally, we demonstrated that this method is applicable to industrial strains and fermentation conditions, improving protein production both in the absence and in the presence of an inducer. CONCLUSIONS: This study demonstrates that overexpression of ACE3 variants enables a high level of protein production in the absence of an inducer, and boosts protein production in the presence of an inducer. It is an efficient approach to increase protein productivity and to reduce manufacturing costs.
RESUMO
STUDY OBJECTIVE: Point-of-care testing reduces time to cardiac marker results in patients evaluated for acute coronary syndromes, yet evidence this translates to a decreased length of stay is lacking. We hypothesized that point-of-care testing decreases length of stay in patients being evaluated for acute coronary syndromes in the emergency department (ED). METHODS: Patients being evaluated for possible acute coronary syndromes at 4 EDs in the United States were randomized to having point-of-care markers as well as central laboratory markers, or central laboratory markers only (laboratory arm). Point-of-care markers were obtained using early serial testing at presentation and at 90, 180, and 360 minutes as required by the treating physician. Evaluation, treatment, and disposition decisions were at the treating physician's discretion. Length of stay was from presentation to the time of departure from the ED, either to an inpatient setting or to home. RESULTS: There were 1,000 patients in each study arm. There were 520 patients discharged home from the ED. Median (interquartile range) time to discharge home was 4.6 hours (3.5 to 6.1 hours) in laboratory patients and 4.5 hours (3.5 to 6.1 hours) in point-of-care patients. Median (interquartile range) time to transfer to an inpatient setting for admitted patients was 5.5 hours (4.2 to 7.5 hours) in laboratory patients, and 5.4 hours (4.1 to 7.3 hours) in point-of-care patients. At one site, time to transfer to the floor was reduced in the point-of-care arm compared with the laboratory arm (difference in medians 0.45 hours; 95% confidence interval [CI] -0.14 to 1.04 hours). At one site, time to ED departure for discharged patients was higher in the point-of-care arm than the laboratory arm (difference in medians 1.25 hours; 95% CI 0.13 to 2.36 hours). CONCLUSION: The effect of point-of-care testing on length of stay in the ED varies between settings. At one site, point-of-care testing decreased time to admission, whereas at another, point-of-care testing increased time to discharge. Potential effects of point-of-care testing on patient throughput should be considered in the full context of ED operations.
Assuntos
Síndrome Coronariana Aguda/diagnóstico , Biomarcadores/sangue , Laboratórios Hospitalares/organização & administração , Tempo de Internação , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Adulto , Idoso , Serviço Hospitalar de Emergência , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
A key step in a chemoenzymatic process for the production of high-purity glycolic acid (GLA) is the enzymatic conversion of glycolonitrile (GLN) to ammonium glycolate using a nitrilase derived from Acidovorax facilis 72W. Protein engineering and over-expression of this nitrilase, combined with optimized fermentation of an E. coli transformant were used to increase the enzyme-specific activity up to 15-fold and the biocatalyst-specific activity up to 125-fold. These improvements enabled achievement of the desired volumetric productivity and biocatalyst productivity for the conversion of GLN to ammonium glycolate.
Assuntos
Acetonitrilas/química , Aminoidrolases/química , Aminoidrolases/metabolismo , Betaproteobacteria/enzimologia , Escherichia coli/enzimologia , Glicolatos/síntese química , Engenharia de Proteínas/métodos , Aminoidrolases/genética , Betaproteobacteria/genética , Escherichia coli/genética , Proteínas Recombinantes/metabolismoRESUMO
OBJECTIVE: The goal of trauma triage is to match resources to the needs of seriously injured patients. The trauma triage literature has used a variety of outcome measures to assess appropriate trauma activation. The objective of this study was to determine the agreement between procedural and nonprocedural outcome measures in a population of seriously injured patients transported to a single trauma center. METHODS: Study authors reviewed all "level 2" trauma activations (January 2002-December 2003) at an American College of Surgeons (ACS) Level 1 trauma center. "Level 2" trauma activations were based on modified ACS Committee on Trauma (COT) triage criteria. Outcomes were classified as nonprocedural (Injury Severity Score [ISS] > 15 and intensive care unit [ICU] admission) and procedural (nonorthopedic emergent surgery, emergency chest tube placement, emergency department intubation, emergency department transfusion, or emergent interventional radiology care). RESULTS: Of 479 patients, five were transferred out of hospital. The remaining 474 were predominantly male (62%), with a mean age of 39.7 years. Their average ISS was 13.2. There were nine deaths. For all subjects, 144 (30%) were admitted to the ICU, 172 (36%) had an ISS > 15, 80 (17%) received an emergent procedure, and 46 (10%) went for emergent surgery. Kappas comparing agreement of ISS > 15 with emergent resuscitation and emergent surgery were 0.31 and 0.15, respectively. Kappas comparing ICU admission with emergent resuscitation and emergent surgery were 0.51 and 0.26, respectively. CONCLUSIONS: We identify moderate to poor agreement between nonprocedural and procedural outcomes of trauma triage in this population.
Assuntos
Avaliação de Resultados em Cuidados de Saúde , Triagem/normas , Ferimentos e Lesões , Adulto , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Michigan , Pessoa de Meia-Idade , Estudos Retrospectivos , Transporte de Pacientes , Centros de Traumatologia , Índices de Gravidade do Trauma , Adulto JovemRESUMO
OBJECTIVES: Some physicians prescribe corticosteroids as adjunctive therapy for patients with migraine headaches to decrease the rate of rebound headache. The efficacy of this practice has not been tested. Our objective is to determine the efficacy of single-dose dexamethasone as adjunctive therapy for emergency medicine patients with migraine headache in preventing headache recurrence at 3 and 30 days posttreatment. METHODS: From November 2004 to November 2005, we conducted a multicenter, double-blinded, placebo-controlled randomized clinical trial of adult patients who met the International Headache Society definition of migraine headache. After informed consent, patients were randomly assigned to one of two groups: receiving either placebo or 24 mg dexamethasone intravenously. To ensure generalizability, all other aspects of patient care were left to the discretion of the emergency physician. Clinical and demographic information was obtained; and patients were subsequently contacted at both 3 and 30 days to determine headache recurrence, current functional disability, and need for return to the ED. Our primary outcome measures were the recurrence of migraine headache at 3 and 30 days. We used Fisher exact to test for statistical significance. RESULTS: A total of 115 patients were enrolled, with 16 patients lost to follow-up at 3 days and 3 additional patients lost at 30 days. Baseline characteristics as well as adverse event profiles were equivalent in both study groups. At 3-day follow-up, 45% (95% confidence interval [CI] 31%-60%) of the placebo group had recurrence of their migraine compared with 35% (95% CI 24%-48%) in the dexamethasone group (P = .68). At 30-day follow-up, this relative reduction in migraine recurrence decreased to a 4% difference between the 2 groups (P = .68). Limitations include small sample size and significant proportion lost to follow-up. CONCLUSION: A single dose of dexamethasone as adjunctive therapy for migraine headache does not decrease the recurrence of migraines at 3 or 30 days.
Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Transtornos de Enxaqueca/prevenção & controle , Prevenção Secundária , Doença Aguda , Adulto , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Transtornos de Enxaqueca/tratamento farmacológico , Resultado do TratamentoRESUMO
The present study was undertaken to provide the foundation for development of genome-scale resources for the fathead minnow (Pimephales promelas), an important model organism widely used in both aquatic toxicology research and regulatory testing. The authors report on the first sequencing and 2 draft assemblies for the reference genome of this species. Approximately 120× sequence coverage was achieved via Illumina sequencing of a combination of paired-end, mate-pair, and fosmid libraries. Evaluation and comparison of these assemblies demonstrate that they are of sufficient quality to be useful for genome-enabled studies, with 418 of 458 (91%) conserved eukaryotic genes mapping to at least 1 of the assemblies. In addition to its immediate utility, the present work provides a strong foundation on which to build further refinements of a reference genome for the fathead minnow.
Assuntos
Cyprinidae/genética , Genoma/genética , Animais , Mapeamento Cromossômico , DNA/genética , Genes , Biblioteca Genômica , Família Multigênica/genética , Valores de Referência , Análise de Sequência de DNARESUMO
Chromosomal mutants were isolated in Escherichia coli that altered carotenoid production from transformed carotenoid biosynthesis genes on a pACYC-derived plasmid (pPCB15). The mutations were mapped by sequencing. One group of mutations appeared to affect the cell metabolism without changing the copy number of the carotenoid synthesis plasmid. The other group of mutations either increased or decreased the copy number of the pPCB15 plasmid as determined by real-time PCR. The copy number change in most mutants was likely specific for ColE1-type plasmids for which copy number is controlled by a small antisense RNA. This collection of host strains would be useful for fine tuning expression of proteins and adjusting production of desired molecules without recloning to different vectors.
Assuntos
Proteínas de Bactérias/genética , Carotenoides/biossíntese , Escherichia coli/isolamento & purificação , Dosagem de Genes , Mutação , Plasmídeos , Proteínas de Bactérias/metabolismo , Biotecnologia/métodos , Cromossomos Bacterianos/genética , Elementos de DNA Transponíveis , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Mutagênese InsercionalRESUMO
PURPOSE: A simple method is needed to risk stratify normotensive patients with pulmonary embolism. We studied whether bedside clinical data can predict in-hospital complications from pulmonary embolism. METHODS: We performed a multicenter derivation phase, followed by validation in a single center. All patients were normotensive; the diagnosis of pulmonary embolism was established by objective imaging. Classification and regression analysis was performed to derive a decision tree from 27 parameters recorded from 207 patients. The validation study was conducted on a separate group of 96 patients to determine the derived criterion's diagnostic accuracy for in-hospital complications (cardiogenic shock, respiratory failure, or death). RESULTS: Mortality in the derivation phase was 4% (n = 8) at 24 hours and 10% (n = 21) at 30 days. A room-air pulse oximetry reading <95% was the most important predictor of death; mortality was 2% (95% confidence interval [CI]: 0% to 6%) in patients with pulse oximetry >or=95% versus 20% (95% CI: 12% to 29%) with pulse oximetry <95%. In the validation phase, the room-air pulse oximetry was <95% at the time of diagnosis in 9 of 10 patients who developed an in-hospital complication (sensitivity, 90%) and >or=95% in 55 of 86 patients without complications (specificity, 64%). CONCLUSION: Mortality from pulmonary embolism in normotensive patients is high. A room-air pulse oximetry reading >or=95% at diagnosis is associated with a significantly lower probability of in-hospital complications from pulmonary embolism.
Assuntos
Hospitalização , Oximetria/normas , Embolia Pulmonar/complicações , Insuficiência Respiratória/prevenção & controle , Choque Cardiogênico/prevenção & controle , Pressão Sanguínea/fisiologia , Humanos , Valor Preditivo dos Testes , Estudos Prospectivos , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Reprodutibilidade dos Testes , Insuficiência Respiratória/etiologia , Medição de Risco/métodos , Sensibilidade e Especificidade , Choque Cardiogênico/etiologia , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To estimate the cost effectiveness of a 7-year police automatic external defibrillator (AED) program in four suburban communities. METHOD: 10-year retrospective study (7/89-7/99) of patients of four suburban communities during two study periods: (1) police first response and advanced life support (ALS) care (No-AED) and; (2) AED equipped police first response (P-AED) with subsequent ALS care. Using the perspective of the communities, we obtained costs of AED program from police agencies. We estimated cost/life saved and cost/year lives saved using decreased time to VF shock by EMS. We performed a sensitivity analysis for estimates of potential benefit using estimated improved survival as a result of decreased EMS response interval and obtained survival data. We used literature-based estimates of life expectancy after cardiac arrest survival to estimate cost/year life saved. We used student's t-test and chi(2) to estimate differences between groups. RESULTS: During the 10-year study period 208 patients met study criteria; (81 No-AED, 128 P-AED). The two groups were not different by patient age, ALS response interval, percent in VF, percent witnessed (WIT), or arrest location. Interval to first defibrillator equipped EMS vehicle arrival was less in the P-AED group (2.0 vs. 5.4 min, P<0.001) as was the interval from the emergency (911) call to first VF shock (6.6 vs. 8.4 min, P=0.02). Survival to DC was not statistically different with P-AED (11.9 vs. 9.9%, P=0.66) but this study was not powered to detect a difference. Estimated cost per life saved with P-AED varied from $23542 to $70342 and cost per year life saved ranged from $1582 to $16060. CONCLUSION: Police AED appears to be a cost-effective intervention in these suburban communities which have relatively rapid EMS response intervals.
Assuntos
Cardioversão Elétrica/economia , Serviços Médicos de Emergência/economia , Promoção da Saúde/economia , Parada Cardíaca/terapia , Idoso , Automação , Reanimação Cardiopulmonar/economia , Reanimação Cardiopulmonar/estatística & dados numéricos , Análise Custo-Benefício , Cardioversão Elétrica/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Parada Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Polícia , Probabilidade , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , População Suburbana , Análise de Sobrevida , Fatores de Tempo , Estados UnidosRESUMO
UNLABELLED: Older people are trained infrequently in cardiopulmonary resuscitation (CPR), yet are more likely to witness a cardiac arrest. Older people who are CPR trained perform CPR when witnessing a cardiac arrest. OBJECTIVE: To assess whether elderly adults (>55 years) who receive chest-compression only cardiopulmonary resuscitation (CC-CPR) training display equivalent skill retention rates compared with those who receive traditional CPR instruction. We also identified factors associated with 3 months skill retention at 3 months in both groups. METHODS: Older adults in a suburban hospital Older Adult Services program were invited to participate in an experimental CPR course. The 2 h course was modelled after the AHA Friends and Family course, and used one of two standardized video scenarios. Seventy four subjects were randomized to CC-CPR (n=36) or traditional CPR (n=38) training. Participation consisted of initial training, followed by a 3 months return videotaped assessment. Three months skill competence was assessed either by consensus between two video evaluators, or the on-site evaluator. Chi square and Kappa tests were used for analysis, and unadjusted odds ratios and 95% confidence intervals are reported. RESULTS: Skill retention assessments were completed on 29 (81%) CC-CPR and 26 (68%) CPR trainees. Subjects were elderly (71.5+/-6.69 years), and had a high rate of previous CPR training (58.0%). Groups were similar in demographic characteristics. After training, participants exhibited high rates of perceived competence (86.4%), although the overall 3 months skill retention was low (43.6%). CC-CPR training resulted in equivalent skill retention rates as compared with traditional CPR training (51.7 vs. 44.4%; P=0.586). No participant factors were associated with skill retention, including age, previous CPR training, education level, medical history, or perceived physical ability to perform. CONCLUSION: We identified low rates of CPR skill retention in this elderly population. CC-CPR instruction was associated with equivalent skill retention rates compared with traditional CPR instruction. No demographic factors were associated with successful skill retention.
Assuntos
Reanimação Cardiopulmonar/métodos , Idoso , Reanimação Cardiopulmonar/educação , Feminino , Parada Cardíaca/terapia , Humanos , Masculino , Projetos Piloto , Pressão , Estudos Prospectivos , Retenção Psicológica , Tórax , Fatores de Tempo , Gravação em VídeoRESUMO
UNLABELLED: Glucocorticoids are an effective treatment for croup, although the most beneficial route of administration remains unclear. Recent studies have concluded that both intramuscular dexamethasone and oral dexamethasone are effective treatments, but there are few data directly comparing the two for moderate-to-severe croup. OBJECTIVES: The authors' primary objective was to determine whether there is a difference in proportion of children with resolution of symptoms attributable to croup at 24 hours, when treated with oral or intramuscular dexamethasone. Secondarily, the authors sought to estimate whether there is a difference in proportion of children with resolution of symptoms attributable to croup at 10 days and to estimate the interval to complete resolution of symptoms between these two routes. METHODS: The authors performed a prospective, randomized, double-blind trial involving children aged 3-84 months with moderate-to-severe croup, presenting to a suburban teaching emergency department (ED). Patients were eligible for enrollment if they had inspiratory stridor or a barky cough and a croup score of 2 or greater after 10-15 minutes of cool mist therapy. The patients were randomized to one of two intervention groups. In both groups, the parents were not present in the treatment room during study drug administration. One group received 0.6 mg/kg of intramuscular dexamethasone and an oral placebo, while the other group received 0.6 mg/kg of oral dexamethasone and direct pressure on their thigh with the hub of a syringe. A nurse placed a Band-Aid on the site of the real or mock injection. Parents were contacted by telephone approximately 1 and 10 days after the index visit to ask about their child's symptoms using a standardized questionnaire. Data were analyzed using an intention-to-treat approach. RESULTS: Of 126 patients eligible, 96 were recruited, with complete follow-up on 95. The groups were similar in all baseline characteristics, treatments received in the ED, and disposition. At 24 hours and 10 days after the visit, there were no statistical differences between the groups for the proportion with stridor, expiratory sounds, barky cough, sleep pattern, the degree of improvement, or the proportion with complete resolution of symptoms at one day. CONCLUSIONS: No statistical differences for any parameters were observed between intramuscular and oral dexamethasone treatments for children with moderate-to-severe croup at 24 hours or at any time the week after treatment. The durations of symptoms were similar between the treatment groups.
Assuntos
Crupe/tratamento farmacológico , Dexametasona/uso terapêutico , Administração Oral , Pré-Escolar , Crupe/classificação , Dexametasona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lactente , Injeções Intramusculares , Masculino , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Older persons are the group most likely to respond to cardiac arrests in private residences. OBJECTIVE: To characterize the knowledge about, attitudes toward, and perceived self-efficacy of older persons in learning and providing cardiopulmonary resuscitation. METHODS: A total of 2743 surveys were mailed to adults 55 years and older who resided in a single Michigan suburb. Data were collected on demographics, medical history, training in and willingness to provide cardiopulmonary resuscitation, and concerns about providing this intervention. RESULTS: The 631 persons (24.6%) who responded were elderly (mean age, 73.5 years) and had a mean of 1.7 occupants per household. More than one third lived alone. Of all respondents, 275 (43.6%) had received training in cardiopulmonary resuscitation, 370 (58.6%) indicated a willingness to learn cardiopulmonary resuscitation, and 412 (65.3%) thought that they had the ability to perform this intervention. Respondents 80 years or younger were significantly more likely than respondents more than 80 years old to be willing to learn cardiopulmonary resuscitation (65.7% vs 19.0%, P < .001) and perceived themselves as able to perform it (73.0% vs 34.0%, P < .001). The absence of mouth-to-mouth ventilation as part of training had minimal impact on the willingness of either age group to receive training (61.2% vs 58.6%, P = .19). Perceived ability to learn and perform cardiopulmonary resuscitation did not vary with the medical history of the respondent or the respondent's spouse. CONCLUSION: Adults 56 to 80 years old perceive themselves as able to perform cardiopulmonary resuscitation and are interested in receiving training.