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1.
J Wildl Dis ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741369

RESUMO

Ranaviruses are pathogens of ectothermic vertebrates (fish, amphibians, and reptiles). Turtles are the most common group of reptiles reported with ranaviral infections. However, there have been no surveys for wild ranaviral infection in any turtles from the suborder Pleurodira, despite ranaviral distributions and experimentally susceptible pleurodiran turtle populations overlapping in several areas, including Australia. We assayed 397 pooled blood samples from six Australian freshwater turtle species collected from five different sites in northern Australia between 2014 and 2019. Historical serologic surveys in the area had found antiranaviral antibodies; however, we did not detect any ranaviral DNA in our samples. Discrepancies between historical serologic and our molecular results may be explained by low viral prevalence during the years that these samples were collected, survivorship bias, or possibly an age class bias in sampling.

2.
Crit Pathw Cardiol ; 21(3): 130-134, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35994721

RESUMO

INTRODUCTION: Patients with atrial fibrillation (AF) are frequently admitted from the emergency department (ED), and when discharged, are not reliably prescribed indicated anticoagulation. We report the impact of a novel computerized ED AF pathway orderset on discharge rate and risk-appropriate anticoagulation in patients with primary AF. METHODS: The orderset included options for rate and rhythm control of primary AF, structured risk assessment for thrombotic complications, recommendations for anticoagulation as appropriate, and follow up with an electrophysiologist. All patients discharged from the ED in whom the AF orderset was utilized over an 18-month period comprised the primary study population. The primary outcome was the rate of appropriate anticoagulation or not according to confirmed CHADS-VASC and HASBLED scores. Additionally, the percentage of primary AF patients discharged directly from the ED was compared in the 18-month periods before and after introduction of the orderset. RESULTS: A total of 56 patients, average age 57.8 years and average initial heart rate 126 beats/minute, were included in the primary analysis. All 56 (100%; 95% confidence interval, 94-100) received guideline-concordant anticoagulation. The discharge rates in the pre- and postorderset implementation periods were 29% and 41%, respectively (95% confidence interval for 12% difference, 5-18). CONCLUSIONS: Our novel AF pathway orderset was associated with 100% guideline-concordant anticoagulation in patients discharged from the ED. Availability of the orderset was associated with a significant increase in the proportion of ED AF patients discharged.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Algoritmos , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Serviço Hospitalar de Emergência , Humanos , Pessoa de Meia-Idade , Alta do Paciente , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
3.
Plant J ; 111(5): 1453-1468, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35816116

RESUMO

Large enzyme families catalyze metabolic diversification by virtue of their ability to use diverse chemical scaffolds. How enzyme families attain such functional diversity is not clear. Furthermore, duplication and promiscuity in such enzyme families limits their functional prediction, which has produced a burgeoning set of incompletely annotated genes in plant genomes. Here, we address these challenges using BAHD acyltransferases as a model. This fast-evolving family expanded drastically in land plants, increasing from one to five copies in algae to approximately 100 copies in diploid angiosperm genomes. Compilation of >160 published activities helped visualize the chemical space occupied by this family and define eight different classes based on structural similarities between acceptor substrates. Using orthologous groups (OGs) across 52 sequenced plant genomes, we developed a method to predict BAHD acceptor substrate class utilization as well as origins of individual BAHD OGs in plant evolution. This method was validated using six novel and 28 previously characterized enzymes and helped improve putative substrate class predictions for BAHDs in the tomato genome. Our results also revealed that while cuticular wax and lignin biosynthetic activities were more ancient, anthocyanin acylation activity was fixed in BAHDs later near the origin of angiosperms. The OG-based analysis enabled identification of signature motifs in anthocyanin-acylating BAHDs, whose importance was validated via molecular dynamic simulations, site-directed mutagenesis and kinetic assays. Our results not only describe how BAHDs contributed to evolution of multiple chemical phenotypes in the plant world but also propose a biocuration-enabled approach for improved functional annotation of plant enzyme families.


Assuntos
Aciltransferases , Solanum lycopersicum , Aciltransferases/metabolismo , Antocianinas/metabolismo , Genoma de Planta/genética , Solanum lycopersicum/genética , Filogenia , Plantas/metabolismo
4.
BMC Ecol Evol ; 22(1): 57, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501685

RESUMO

BACKGROUND: Approximately 50% of freshwater turtles worldwide are currently threatened by habitat loss, rural development and altered stream flows. Paradoxically, reptiles are understudied organisms, with many species lacking basic geographic distribution and abundance data. The iconic Irwin's turtle, Elseya irwini, belongs to a unique group of Australian endemic freshwater turtles capable of cloacal respiration. Water resource development, increased presence of saltwater crocodiles and its cryptic behaviour, have made sampling for Irwin's turtle in parts of its range problematic, resulting in no confirmed detections across much of its known range for > 25 years. Here, we used environmental DNA (eDNA) analysis for E. irwini detection along its historical and contemporary distribution in the Burdekin, Bowen and Broken River catchments and tributaries. Five replicate water samples were collected at 37 sites across those three river catchments. Environmental DNA was extracted using a glycogen-aided precipitation method and screened for the presence of E. irwini through an eDNA assay targeting a 127 base pair-long fragment of the NADH dehydrogenase 4 (ND4) mitochondrial gene. RESULTS: Elseya irwini eDNA was detected at sites within its historic distribution in the lower Burdekin River, where the species had not been formally recorded for > 25 years, indicating the species still inhabits the lower Burdekin area. We also found higher levels of E. iriwni eDNA within its contemporary distribution in the Bowen and Broken Rivers, matching the prevailing scientific view that these areas host larger populations of E. irwini. CONCLUSIONS: This study constitutes the first scientific evidence of E. irwini presence in the lower Burdekin since the original type specimens were collected as part of its formal description, shortly after the construction of the Burdekin Falls Dam. From the higher percentage of positive detections in the upper reaches of the Broken River (Urannah Creek), we conclude that this area constitutes the core habitat area for the species. Our field protocol comprises a user-friendly, time-effective sampling method. Finally, due to safety risks associated with traditional turtle sampling methods in the Burdekin River (e.g., estuarine crocodiles) we propose eDNA sampling as the most pragmatic detection method available for E. irwini.


Assuntos
DNA Ambiental , Tartarugas , Animais , Austrália , DNA Ambiental/genética , Ecossistema , Rios , Tartarugas/genética
5.
Appl Clin Inform ; 13(2): 391-397, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35294986

RESUMO

BACKGROUND: Hospitals are increasingly replacing pagers with clinical texting systems that allow users to use smartphones to send messages while maintaining compliance for privacy and security. As more institutions adopt such systems, the need to understand the impact of such transitions on team communication becomes ever more significant. METHODS: We conducted focus groups with hospitalists and individual interviews with nurses at one academic medical center in the Midwest. All interviews and focus groups were audiorecorded, transcribed, and deidentified for analysis. All transcripts and notes were independently read by two members of the research team and coded for themes. RESULTS: Twenty-one hospitalists and eight nurses participated in the study. Although study participants spoke favorably of texting, they identified more dissatisfactions with texting than benefits. There were disagreements regarding appropriate texting practices both within and between the hospitalists and nurses. CONCLUSION: Despite the benefits of texting, there is room for improving team communication and understanding in the realm of clinical texting. A lack of shared understanding regarding when and how to use texting may require long-term solutions that address teamwork and appropriateness.


Assuntos
Envio de Mensagens de Texto , Atitude do Pessoal de Saúde , Comunicação , Grupos Focais , Hospitais , Humanos
6.
J Emerg Med ; 62(2): 145-153, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35045940

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with respiratory symptoms and renal effects. Data regarding fluid resuscitation and kidney injury in COVID-19 are lacking, and understanding this relationship is critical. OBJECTIVES: To determine if there is an association between fluid volume administered in 24 h and development of renal failure in COVID-19 patients. METHODS: Retrospective chart review; 14 hospitals in Indiana. Included patients were adults admitted between March 11, 2020 and April 13, 2020 with a positive test for severe acute respiratory syndrome coronavirus 2 within 3 days of admission. Patients requiring renal replacement therapy prior to admission were excluded. Volumes and types of resuscitative intravenous fluids in the first 24 h were obtained with demographics, medical history, and other objective data. The primary outcome was initiation of renal replacement therapy. Logistic regression modeling was utilized in creating multivariate models for determining factors associated with the primary outcome. RESULTS: The fluid volume received in the first 24 h after hospital admission was associated with initiation of renal replacement therapy in two different multivariate logistic regression models. An odds ratio of 1.42 (95% confidence interval 1.01-1.99) was observed when adjusting for age, heart failure, obesity, creatinine, bicarbonate, and total fluid volume. An odds ratio of 1.45 (95% confidence interval 1.02-2.05) was observed when variables significant in univariate analysis were adjusted for. CONCLUSIONS: Each liter of intravenous fluid administered to patients with COVID-19 in the first 24 h of presentation was independently associated with an increased risk for initiation of renal replacement therapy, supporting judicious fluid administration in patients with this disease.


Assuntos
Injúria Renal Aguda , COVID-19 , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adulto , Hidratação/efeitos adversos , Humanos , Terapia de Substituição Renal , Estudos Retrospectivos , SARS-CoV-2
7.
Ecol Evol ; 11(20): 13780-13792, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34707817

RESUMO

Installation of feral pig (Sus scrofa) exclusion fences to conserve and rehabilitate coastal floodplain habitat for fish production and water quality services remains untested. Twenty-one floodplain and riverine wetlands in the Archer River catchment (north Queensland) were surveyed during postwet (June-August) and late-dry season (November-December) in 2016, 2017, and 2018, using a fyke net soaked overnight (~14-15 hr) to test: (a) whether the fish assemblage are similar in wetlands with and without fences; and (b) whether specific environmental conditions influence fish composition between fenced and unfenced wetlands. A total of 6,353 fish representing twenty-six species from 15 families were captured. There were no wetland differences in fish assemblages across seasons, years and for fenced and unfenced (PERMANOVA, Pseudo-F < 0.589, p < .84). Interestingly, the late-dry season fish were far smaller compared to postwet season fish: a strategy presumably in place to maximize rapid disposal following rain and floodplain connectivity. In each wetland, a calibrated Hydrolab was deployed (between 2 and4 days, with 20 min logging) in the epilimnion (0.2 m) and revealed distinct diel water quality cycling of temperature, dissolved oxygen and pH (conductivity represented freshwater wetlands), which was more obvious in the late-dry season survey because of extreme summer conditions. Water quality varied among wetlands in terms of the daily amplitude and extent of daily photosynthesis recovery, which highlights the need to consider local conditions and that applying general assumptions around water quality conditions for these types of wetlands is problematic for managers. Though many fish access wetlands during wet season connection, the seasonal effect of reduced water level conditions seems more overimprovised when compared to whether fences are installed, as all wetlands supported few, juvenile, or no fish species because they had dried completely regardless of the presence of fences.

8.
Acad Emerg Med ; 28(5): 511-518, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675164

RESUMO

BACKGROUND: Patients with COVID-19 can present to the emergency department (ED) at any point during the spectrum of illness, making it difficult to predict what level of care the patient will ultimately require. Admission to a ward bed, which is subsequently upgraded within hours to an intensive care unit (ICU) bed, represents an inability to appropriately predict the patient's course of illness. Predicting which patients will require ICU care within 24 hours would allow admissions to be managed more appropriately. METHODS: This was a retrospective study of adults admitted to a large health care system, including 14 hospitals across the state of Indiana. Included patients were aged ≥ 18 years, were admitted to the hospital from the ED, and had a positive polymerase chain reaction (PCR) test for COVID-19. Patients directly admitted to the ICU or in whom the PCR test was obtained > 3 days after hospital admission were excluded. Extracted data points included demographics, comorbidities, ED vital signs, laboratory values, chest imaging results, and level of care on admission. The primary outcome was a combination of either death or transfer to ICU within 24 hours of admission to the hospital. Data analysis was performed by logistic regression modeling to determine a multivariable model of variables that could predict the primary outcome. RESULTS: Of the 542 included patients, 46 (10%) required transfer to ICU within 24 hours of admission. The final composite model, adjusted for age and admission location, included history of heart failure and initial oxygen saturation of <93% plus either white blood cell count > 6.4 or glomerular filtration rate < 46. The odds ratio (OR) for decompensation within 24 hours was 5.17 (95% confidence interval [CI] = 2.17 to 12.31) when all criteria were present. For patients without the above criteria, the OR for ICU transfer was 0.20 (95% CI = 0.09 to 0.45). CONCLUSIONS: Although our model did not perform well enough to stand alone as a decision guide, it highlights certain clinical features that are associated with increased risk of decompensation.


Assuntos
COVID-19 , Adolescente , Adulto , Cuidados Críticos , Serviço Hospitalar de Emergência , Humanos , Unidades de Terapia Intensiva , Admissão do Paciente , Estudos Retrospectivos , SARS-CoV-2
9.
Emerg Top Life Sci ; 5(2): 221-230, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33538291

RESUMO

Structural biologists rely on X-ray crystallography as the main technique for determining the three-dimensional structures of macromolecules; however, in recent years, new methods that go beyond X-ray-based technologies are broadening the selection of tools to understand molecular structure and function. Simultaneously, national facilities are developing programming tools and maintaining personnel to aid novice structural biologists in de novo structure determination. The combination of X-ray free electron lasers (XFELs) and serial femtosecond crystallography (SFX) now enable time-resolved structure determination that allows for capture of dynamic processes, such as reaction mechanism and conformational flexibility. XFEL and SFX, along with microcrystal electron diffraction (MicroED), help side-step the need for large crystals for structural studies. Moreover, advances in cryogenic electron microscopy (cryo-EM) as a tool for structure determination is revolutionizing how difficult to crystallize macromolecules and/or complexes can be visualized at the atomic scale. This review aims to provide a broad overview of these new methods and to guide readers to more in-depth literature of these methods.


Assuntos
Elétrons , Lasers , Cristalografia por Raios X , Biologia Molecular , Raios X
10.
J Med Virol ; 93(5): 2883-2889, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33448423

RESUMO

INTRODUCTION: The rate of bacterial coinfection with SARS-CoV-2 is poorly defined. The decision to administer antibiotics early in the course of SARS-CoV-2 infection depends on the likelihood of bacterial coinfection. METHODS: We performed a retrospective chart review of all patients admitted through the emergency department with confirmed SARS-CoV-2 infection over a 6-week period in a large healthcare system in the United States. Blood and respiratory culture results were abstracted and adjudicated by multiple authors. The primary outcome was the rate of bacteremia. We secondarily looked to define clinical or laboratory features associated with bacteremia. RESULTS: There were 542 patients admitted with confirmed SARS-CoV-2 infection, with an average age of 62.8 years. Of these, 395 had blood cultures performed upon admission, with six true positive results (1.1% of the total population). An additional 14 patients had positive respiratory cultures treated as true pathogens in the first 72 h. Low blood pressure and elevated white blood cell count, neutrophil count, blood urea nitrogen, and lactate were statistically significantly associated with bacteremia. Clinical outcomes were not statistically significantly different between patients with and without bacteremia. CONCLUSIONS: We found a low rate of bacteremia in patients admitted with confirmed SARS-CoV-2 infection. In hemodynamically stable patients, routine antibiotics may not be warranted in this population.


Assuntos
Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , Coinfecção/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Bacteriemia/terapia , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/terapia , COVID-19/diagnóstico , COVID-19/terapia , Coinfecção/diagnóstico , Coinfecção/terapia , Feminino , Hospitalização , Hospitais , Humanos , Indiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento
11.
Acad Emerg Med ; 27(7): 646-647, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32329954

Assuntos
Pacientes , Troponina , Idoso , Humanos
12.
Acad Emerg Med ; 27(1): 6-14, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31854117

RESUMO

BACKGROUND: Elderly patients presenting to the emergency department (ED) with nonspecific complaints (NSCs) often undergo troponin testing to assess for atypical acute coronary syndrome (ACS). However, the rate of ACS and utility of troponin testing in this population is unknown. We sought to determine the rate of ACS and diagnostic yield of troponin testing in elderly patients with NSCs. METHODS: We retrospectively identified all patients aged ≥ 65 years triaged in the ED with NSCs from January 1, 2017, to June 30, 2017. NSCs were defined a priori and included complaints such as weakness, dizziness, or fatigue. NSCs were verified in ED provider notes by trained abstractors blind to testing results. Exclusions were focal chief complaint in provider notes, fever, and no troponin ordered. ACS was strictly defined and independently adjudicated by two trained physician researchers blind to the study hypothesis. We calculated the proportion of patients with ACS within 30 days and the test characteristics of troponin to diagnose ACS. RESULTS: Screening identified 1,146 encounters, and 552 were excluded for fever or focal chief complaints in the provider notes. Of the remaining 594 patients, troponin was ordered in 412 (69%), comprising the study cohort. The mean (±SD) age was 78.7 (±8.3) years, with 58% female and 75% admitted. Troponin elevation occurred in 81 patients (20%). ACS occurred in 5 of 412 (1.2%). Troponin was 100% sensitive (95% confidence interval [CI] = 48% to 100%) and 81% specific (95% CI = 77% to 85%) for ACS. Of patients with elevated troponin, 93.8% were false positives (no ACS). All patients with troponin elevation were admitted, but only one underwent angiography and no patients received reperfusion therapy. CONCLUSIONS: While consideration for ACS is prudent in selected elderly patients with NSCs, ACS was rare and no patients received reperfusion therapy. Given the false-positive rate in our study, our results may not support routine troponin testing for ACS in this population.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Troponina/sangue , Síndrome Coronariana Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Técnicas de Laboratório Clínico/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Estudos Retrospectivos
13.
Ann Emerg Med ; 75(3): 329-338, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31591013

RESUMO

STUDY OBJECTIVE: There is a paucity of evidence to guide the diagnostic evaluation of emergency department (ED) patients presenting after nonfatal strangulation (manual strangulation or near hanging). We seek to define the rate of serious injuries in alert strangled patients and determine which symptoms and examination findings, if any, predict such injuries. METHODS: Using prospectively populated databases and electronic medical record review, we performed a retrospective analysis of alert strangled patients treated in the ED of an academic Level I trauma center. Exclusions were Glasgow Coma Scale (GCS) score less than 13, younger than 16 years, and interhospital transfers. Trained researchers used structured forms to abstract demographics, symptoms, examination findings, radiology and operative findings, and final diagnoses. Injuries requiring greater than 24 hours' observation or specific treatment (surgery, procedure, specific medication) were considered clinically important. The electronic medical record was searched for 30 days after presentation to identify missed injuries. RESULTS: Advanced imaging (computed tomography or magnetic resonance maging) was obtained in 60%. Injuries were identified in 6 patients (1.7%, 95% CI, 0.7% to 3.6%). Two injuries were clinically important (0.6%, 95% CI, 0.1% to 2.0%). Both were cervical artery dissections with no neurologic deficits, treated with aspirin. No additional injuries were identified within 30 days or at next medical contact. Of 343 uninjured patients, 291 (85%) had documented medical follow up confirming the absence of any new diagnosis of injury or stroke. The small number of injuries precluded analyses of associations. CONCLUSION: Alert, strangled patients had a low rate of injuries. All patients with neck injuries had concerning findings besides neck pain; specifically, GCS score less than 15 or dysphagia. Our findings suggest, but do not prove, that a selective imaging strategy is safe in alert patients after strangulation findings besides neck pain.


Assuntos
Asfixia/diagnóstico , Lesões do Pescoço/diagnóstico , Adulto , Asfixia/etiologia , Asfixia/patologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Lesões das Artérias Carótidas/diagnóstico , Lesões das Artérias Carótidas/diagnóstico por imagem , Lesões das Artérias Carótidas/patologia , Angiografia por Tomografia Computadorizada , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pescoço/irrigação sanguínea , Pescoço/diagnóstico por imagem , Pescoço/patologia , Lesões do Pescoço/diagnóstico por imagem , Lesões do Pescoço/etiologia , Lesões do Pescoço/patologia , Estudos Retrospectivos , Tentativa de Suicídio , Violência , Adulto Jovem
14.
J Biol Chem ; 294(45): 16855-16864, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31575658

RESUMO

To modulate responses to developmental or environmental cues, plants use Gretchen Hagen 3 (GH3) acyl acid amido synthetases to conjugate an amino acid to a plant hormone, a reaction that regulates free hormone concentration and downstream responses. The model plant Arabidopsis thaliana has 19 GH3 proteins, of which 8 have confirmed biochemical functions. One Brassicaceae-specific clade of GH3 proteins was predicted to use benzoate as a substrate and includes AtGH3.7 and AtGH3.12/PBS3. Previously identified as a 4-hydroxybenzoic acid-glutamate synthetase, AtGH3.12/PBS3 influences pathogen defense responses through salicylic acid. Recent work has shown that AtGH3.12/PBS3 uses isochorismate as a substrate, forming an isochorismate-glutamate conjugate that converts into salicylic acid. Here, we show that AtGH3.7 and AtGH3.12/PBS3 can also conjugate chorismate to cysteine and glutamate, which act as precursors to aromatic amino acids and salicylic acid, respectively. The X-ray crystal structure of AtGH3.12/PBS3 in complex with AMP and chorismate at 1.94 Å resolution, along with site-directed mutagenesis, revealed how the active site potentially accommodates this substrate. Examination of Arabidopsis knockout lines indicated that the gh3.7 mutants do not alter growth and showed no increased susceptibility to the pathogen Pseudomonas syringae, unlike gh3.12 mutants, which were more susceptible than WT plants, as was the gh3.7/gh3.12 double mutant. The findings of our study suggest that GH3 proteins can use metabolic precursors of aromatic amino acids as substrates.


Assuntos
Aminoácidos Aromáticos/metabolismo , Brassicaceae/enzimologia , Ácido Corísmico/metabolismo , Ligases/metabolismo , Ácido Salicílico/metabolismo , Arabidopsis/enzimologia , Domínio Catalítico , Cinética , Ligases/química , Ligases/genética , Modelos Moleculares , Mutação , Especificidade da Espécie , Especificidade por Substrato
15.
Nat Commun ; 10(1): 3432, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366889

RESUMO

Nonribosomal peptide synthetases produce diverse natural products using a multidomain architecture where the growing peptide, attached to an integrated carrier domain, is delivered to neighboring catalytic domains for bond formation and modification. Investigation of these systems can lead to the discovery of new structures, unusual biosynthetic transformations, and to the engineering of catalysts for generating new products. The antimicrobial ß-lactone obafluorin is produced nonribosomally from dihydroxybenzoic acid and a ß-hydroxy amino acid that cyclizes into the ß-lactone during product release. Here we report the structure of the nonribosomal peptide synthetase ObiF1, highlighting the structure of the ß-lactone-producing thioesterase domain and an interaction between the C-terminal MbtH-like domain with an upstream adenylation domain. Biochemical assays examine catalytic promiscuity, provide mechanistic insight, and demonstrate utility for generating obafluorin analogs. These results advance our understanding of the structural cycle of nonribosomal peptide synthetases and provide insights into the production of ß-lactone natural products.


Assuntos
Burkholderia/genética , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Vias Biossintéticas/fisiologia , Burkholderia/metabolismo , Domínio Catalítico/genética , Cristalografia por Raios X , Lactonas/metabolismo , Modelos Moleculares
16.
AMIA Jt Summits Transl Sci Proc ; 2019: 656-664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31259021

RESUMO

Despite efforts aimed at improving the integration of clinical data from health information exchanges (HIE) and electronic health records (EHR), interoperability remains limited. Barriers due to inefficiencies and workflow interruptions make using HIE data during care delivery difficult. Capitalizing on the development of the Fast Healthcare Interoperability Resource (FHIR) specification, we designed and developed a Chest Pain Dashboard that integrates HIE data into EHRs. This Dashboard was implemented in one emergency department (ED) of Indiana University Health in Indiana. In this paper, we present the preliminary findings from a mixed-methods evaluation of the Dashboard. A difference-in-difference analysis suggests that the ED with the Dashboard implementation resulted in a significant increase in HIE use compared to EDs without. This finding was supported by qualitative interviews. While these results are encouraging, we also identified areas for improvement. FHIR-based solutions may offer promising approaches to encourage greater accessibility and use of HIE data.

17.
J Emerg Med ; 55(6): 780-787, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316621

RESUMO

BACKGROUND: Syncope is a common presentation in the emergency department (ED). The differential diagnosis is long and includes benign conditions as well as acute life threats, such as dysrhythmias or pulmonary embolism. OBJECTIVE: The specific goals of this review are twofold: 1) to define the diagnostic utility of orthostatic vital signs (OVS) as a test for orthostatic syncope, and 2) to determine whether OVS help diagnose or exclude life-threatening causes of syncope in ED patients. METHODS: Three prospective cohort studies plus 2017 national guidelines for syncope management were identified, reviewed, and critically appraised. RESULTS: This literature review found that orthostatic hypotension is common among ED patients with syncope and is often diagnosed as the cause of syncope. CONCLUSIONS: OVS measurements do not, in isolation, reliably diagnose or exclude orthostatic syncope, nor do they appear to have value in ruling out life-threatening causes of syncope.


Assuntos
Serviço Hospitalar de Emergência , Hipotensão Ortostática/diagnóstico , Síncope/diagnóstico , Sinais Vitais , Diagnóstico Diferencial , Humanos
18.
J Fish Biol ; 93(4): 723-728, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29968260

RESUMO

Acute thermal and asphyxia exposure risks for freshwater fish occupying three tropical wetland typologies were examined. Field water-quality data revealed that fish in wetlands grazed by pigs had the highest exposure risks, because they are shallow and heavily damaged by pig activities. In contrast, with the exception is dissolved oxygen (which still reached critical conditions because of aquatic vegetation respiration), deeper permanent and pig-managed wetlands provides the best opportunity for the same fish species to survive in a heavily pig-modified tropical landscape.


Assuntos
Asfixia/veterinária , Peixes/fisiologia , Estresse Fisiológico , Suínos , Áreas Alagadas , Animais , Asfixia/etiologia , Água Doce , Temperatura Alta , Oxigênio/fisiologia , Queensland
19.
Acad Emerg Med ; 25(3): 293-300, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29218817

RESUMO

BACKGROUND: Patients at low risk for acute coronary syndrome are frequently admitted for observation and cardiac testing, resulting in substantial burden and cost to the patient and the health care system. OBJECTIVES: The purpose of this investigation was to measure the effect of the Chest Pain Choice (CPC) decision aid on overall health care utilization as well as utilization of specific services both during the index emergency department (ED) visit and in the subsequent 45 days. METHODS: This was a planned secondary analysis of data from a pragmatic multicenter randomized trial of shared decision making in adults presenting to the ED with chest pain who were being considered for observation unit admission for cardiac stress testing or coronary computed tomography angiography. The trial compared an intervention group engaged in shared decision making facilitated by the CPC decision aid to a control group receiving usual care. Hospital-level billing data were used to measure utilization for the index ED visit and during the following 45 days. Patients in both groups also were asked to keep a diary recording health care utilization over the same 45-day period. Outcomes assessed included length of time in the ED and observation, ED visits, office visits, hospitalizations, testing, imaging, and procedures. RESULTS: Of the 898 patients included in the original trial, we were able to contact 834 (92.9%) patients for 45-day health care diary review. There was no difference in patient-reported health care utilization between the study arms. Hospital-level billing data were obtained for all 898 (100%) patients. During the initial ED visit the length of stay (LOS) was similar, and there was no difference in the frequency of observation unit admission between study arms. However, the mean observation unit LOS was 95 minutes (95% confidence interval [CI] = 40.8-149.8) shorter in the CPC arm and the mean number of tests was lower in the CPC arm (decrease in 19.4 imaging studies per 100 patients, 95% CI = 15.5-23.3). When evaluating the entire encounter and follow-up period, the intervention arm underwent fewer tests (decrease in 125.6 tests per 100 patients, 95% CI = 29.3-221.6). More specifically, there were fewer advanced cardiac imaging tests completed (25.8 fewer per 100 patients, 95% CI = 3.74-47.9) in the intervention arm. CONCLUSIONS: Shared decision making in low-risk chest pain can lead to decreased diagnostic testing without worsening outcomes measured over 45 days.


Assuntos
Dor no Peito/diagnóstico , Tomada de Decisões , Técnicas de Apoio para a Decisão , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos
20.
Med Decis Making ; 38(1): 69-78, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28525723

RESUMO

BACKGROUND: We test the hypotheses that use of the Chest Pain Choice (CPC) decision aid (DA) would be similarly effective in potentially vulnerable subgroups but increase knowledge more in patients with higher education and trust in physicians more in patients from racial minority groups. METHODS: This was a secondary analysis of a multicenter randomized trial in adults with chest pain potentially due to acute coronary syndrome. The trial compared an intervention group engaged in shared decision making (SDM) using CPC to a control group receiving usual care (UC). We assessed for subgroup effects based on age, sex, race, income, insurance, education, literacy, and numeracy. We dichotomized each characteristic and tested for interactions using regression models with indicators for arm assignment and study site. RESULTS: Of 898 patients (451 DA, 447 UC), over 50% were female, over one-third were black, nearly one-third had a high school education or less, and over 60% had "low" health literacy. The DA did not increase knowledge more in patients with higher education ( P for interaction = 0.06) but did increase knowledge more in the "typical" than in the "low" numeracy subgroup (10.6% v. 4.7%, absolute difference [AD] = 5.9%, P for interaction = 0.025). The DA did not significantly increase patient trust in physicians in racial minorities ( P for interaction = 0.06) but did increase trust more in patients with "low" literacy compared with those with "typical" literacy (3.7% v. -1.4%, AD = 5.1, P for interaction = 0.011). CONCLUSIONS: CPC benefited all sociodemographic groups to a similar extent, with greater knowledge transfer in patients with higher numeracy and greater physician trust in patients with "low" health literacy. Tailoring SDM interventions to patient characteristics may be necessary for optimal effectiveness.


Assuntos
Dor no Peito/terapia , Tomada de Decisões , Técnicas de Apoio para a Decisão , Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde , Adulto , Fatores Etários , Idoso , Comportamento de Escolha , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Participação do Paciente , Grupos Raciais , Fatores Sexuais , Fatores Socioeconômicos , Confiança
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