RESUMO
This study sought to determine whether rap expertise is associated with enhanced knowledge of psychoacoustic similarity. Using a stimulus composed of pseudo-word assonantal half-rhyme triplets (e.g., freet/speet//yeek), expert improvisational rap lyricists were compared to laypersons (non-lyricists) in their judgments of half-rhyme acceptability. According to both a perception-based and a linguistic feature-based measure of psychoacoustic similarity, lyricists were distinct from non-lyricists in the rates at which they found half-rhymes acceptable, and in how group responses were correlated with the similarity measures. Data indicate that, compared to non-lyricists, lyricists' half-rhyme acceptance rates are more highly correlated with linguistic features that have more robust perceptual cues. Evidence suggests that lyricists and non-lyricists employ different strategies for determining the acceptability of half-rhymes, and that lyricists might be more sensitive or attuned to similar aspects of speech sounds.
Assuntos
Julgamento , Percepção da Fala , Humanos , Psicoacústica , Fonética , Sinais (Psicologia)RESUMO
OBJECTIVE: Pediatric procedural sedation (PPS) is used to maintain children's safety, comfort, and cooperation during emergency department procedures. Our objective was to gather data describing PPS practice across the United States to highlight the variations in practice and adherence to National Guidelines. METHODS: We performed a nationwide survey of PPS practitioners using a secure web-based software program. A link to the survey was sent to all subscribers of a pediatric emergency medicine listserv. We collected participant demographics, their PPS approach for personnel, monitoring, equipment, postsedation observation, and side effects, as well as providers' medication preferences for 3 common PPS scenarios. RESULTS: We received 211 completed surveys from 34 States. There were 20.6% respondents that were based in New York, 83.4% were pediatric emergency medicine attendings, and 91.7% were based in the United States teaching hospitals. Our participants learned PPS by various methods, most commonly: observation of at least 10 PPS (29.9%); self-study (24.8%); and classroom lectures (24.5%). Seventy-seven percent of our participants reported no body mass index cutoff to do PPS. There were 31.5% of our participants that observe children after PPS up to 1 hour, 30.1% up to 2 hours. There were 67.7% of the PPS providers that were a separate person from the practitioner doing the procedure, and 98.2% required a separate trained nurse to be present for monitoring. There were 92.6% of PPS providers that measure end-tidal carbon dioxide (ETCO2) during the sedation. Most PPS providers reported having no reversal agents (71.4%) and no defibrillator (65.9%) at bedside. For the abscess drainage scenario, 22% of participants preferred local anesthetic alone, and 22.5% preferred utilizing local anesthetic in combination with intravenous ketamine. For a forearm fracture reduction scenario, 62.8% of participants would choose intravenous ketamine alone. For the laceration repair scenario, the most favored drug combination was local anesthesia + intranasal midazolam by 39.8% of participants. CONCLUSIONS: Our study demonstrates a wide variability in several aspects of PPS and low adherence to national PPS guidelines.
Assuntos
Ketamina , Medicina de Emergência Pediátrica , Criança , Sedação Consciente , Serviço Hospitalar de Emergência , Humanos , Midazolam , Estados UnidosRESUMO
Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors, and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly). The reaction kinetics suggested that GlyGly may function as an acceptor molecule for gingipain-catalyzed transpeptidation. Purified gingipains and P. gingivalis whole cells were used to digest selected substrates including human hemoglobin in the presence or absence of peptide acceptors. Mass spectrometric analysis of the substrates digested with gingipains in the presence of GlyGly showed that transpeptidation outcompeted hydrolysis, whereas the trypsin-digested controls exhibited predominantly hydrolysis activity. The transpeptidation levels increased with increasing concentration of GlyGly. Purified gingipains and whole cells exhibited extensive transpeptidation activities on human hemoglobin. All hemoglobin cleavage sites were found to be suitable for GlyGly transpeptidation, and this transpeptidation enhanced hemoglobin digestion. The transpeptidation products were often more abundant than the corresponding hydrolysis products. In the absence of GlyGly, hemoglobin peptides produced during digestion were utilized as acceptors leading to the detection of up to 116 different transpeptidation products in a single reaction. P. gingivalis cells were able to digest hemoglobin faster when acceptor peptides derived from human serum albumin were included in the reaction, suggesting that gingipain-catalyzed transpeptidation may be relevant for substrates encountered in vivo. The transpeptidation of host proteins in vivo may potentially lead to the breakdown of immunological tolerance, culminating in autoimmune reactions.
Assuntos
Adesinas Bacterianas/metabolismo , Cisteína Endopeptidases/metabolismo , Peptidil Transferases/metabolismo , Porphyromonas gingivalis/enzimologia , Autoimunidade , Cisteína Endopeptidases Gingipaínas , Hemoglobinas/metabolismo , Humanos , Proteólise , Fatores de Virulência/metabolismoRESUMO
OBJECTIVES: A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). METHODS: MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. RESULTS: Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. CONCLUSION: Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management.
Assuntos
Ablação por Cateter/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Temperatura Alta/efeitos adversos , Terapia a Laser/efeitos adversos , Veia Safena/cirurgia , Varizes/cirurgia , Trombose Venosa/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Veia Safena/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Varizes/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagemRESUMO
OBJECTIVE: Satellite pediatric emergency departments (PEDs) have emerged as a strategy to increase patient capacity. We sought to determine the impact on patient visits, physician fee collections, and value of emergency department (ED) time at the primary PED after opening a nearby satellite PED. We also illustrate the spatial distribution of patient demographics and overlapping catchment areas for the primary and satellite PEDs using geographical information system. METHODS: A structured, financial retrospective review was conducted. Aggregate patient demographic data and billing data were collected regarding physician fee charges, collections, and patient visits for both PEDs. All ED visits from January 2009 to December 2013 were analyzed. Geographical information system mapping using ArcGIS mapped ED patient visits. RESULTS: Patient visits at the primary PED were 53,050 in 2009 before the satellite PED opened. The primary PED visits increased after opening the satellite PED to 55,932 in 2013. The satellite PED visits increased to 21,590 in 2013. Collections per visit at the primary PED decreased from $105.13 per visit in 2011 to $86.91 per visit in 2013. Total collections at the satellite PED decreased per visit from $155.41 per visit in 2011 to $128.53 per visit in 2013. CONCLUSIONS: After opening a nearby satellite PED, patient visits at the primary PED did not substantially decrease, suggesting that there was a previously unrecognized demand for PED services. The collections per ED visit were greater at the satellite ED, likely due to a higher collection rate.
Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Satélites/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Criança , Demografia , Serviço Hospitalar de Emergência/economia , Feminino , Hospitais Pediátricos/economia , Hospitais Satélites/economia , Humanos , Masculino , Estudos RetrospectivosRESUMO
Aneurysmal degeneration of the superior mesenteric artery (SMA) is a rare clinical finding, estimated to affect <1% of the general population in postmortem studies. Due to the rare prevalence of aneurysms affecting the SMA, there are no clear or definitive published consensus guidelines for its management at presentation, with both surgical and endovascular options described. An aberrant or replaced right hepatic artery (RRHA) is thought to affect 10-15% of the population. The prevalence of both conditions presenting concomitantly is unknown, but undoubtedly even rarer. We describe the successful management of a symptomatic SMA aneurysm with an RRHA emerging from the aneurysmal sac presenting to our vascular unit. This was repaired via an open surgical approach with SMA aneurysmectomy and interposition grafting using reversed vein with preservation of RHA liver perfusion via a novel reconstruction option. This case highlights the challenge that visceral aneurysms pose, especially when simple or orthodox reconstruction options are limited due to rare or unusual anatomy.
Assuntos
Aneurisma/complicações , Artéria Hepática/anormalidades , Artéria Mesentérica Superior , Malformações Vasculares/complicações , Anastomose Cirúrgica , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Angiografia por Tomografia Computadorizada , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/cirurgia , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/cirurgia , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica , Veia Safena/transplante , Resultado do Tratamento , Enxerto Vascular/métodos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/cirurgiaRESUMO
Tryptic digestion of the calcium-sensitive caseins yields casein phosphopeptides (CPP) that contain clusters of phosphorylated seryl residues. The CPP stabilize calcium and phosphate ions through the formation of complexes. The calcium phosphate in these complexes is biologically available for intestinal absorption and remineralization of subsurface lesions in tooth enamel. We have studied the structure of the complexes formed by the CPP with calcium phosphate using a variety of nuclear magnetic resonance (NMR) techniques. Translational diffusion measurements indicated that the ß-CN(1-25)-ACP nanocomplex has a hydrodynamic radius of 1.526 ± 0.044 nm at pH 6.0, which increases to 1.923 ± 0.082 nm at pH 9.0. (1)H NMR spectra were well resolved, and (3)JH(N)-H(α) measurements ranged from a low of 5.5 Hz to a high of 8.1 Hz. Total correlation spectroscopy and nuclear Overhauser effect spectroscopy spectra were acquired and sequentially assigned. Experiments described in this paper have allowed the development of a structural model of the ß-CN(1-25)-amorphous calcium phosphate nanocomplex.
Assuntos
Fosfatos de Cálcio/química , Caseínas/química , Sequência de Aminoácidos , Animais , Caseínas/farmacocinética , Bovinos , Humanos , Absorção Intestinal , Micelas , Modelos Moleculares , Complexos Multiproteicos/química , Nanoestruturas/química , Ressonância Magnética Nuclear Biomolecular , Fosfopeptídeos/químicaAssuntos
Cálculos/terapia , Drenagem , Nefrotomia , Abscesso do Psoas/terapia , Pielonefrite Xantogranulomatosa/complicações , Cálculos/diagnóstico por imagem , Cálculos/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/etiologia , Pielonefrite Xantogranulomatosa/diagnóstico por imagem , Radiografia Intervencionista , Resultado do TratamentoRESUMO
The repair of early dental caries lesions has been demonstrated by the application of the remineralisation technology based on casein phosphopeptide-stabilised amorphous calcium phosphate complexes (CPP-ACP). These complexes consist of an amorphous calcium phosphate mineral phase stabilised and encapsulated by the self-assembly of milk-derived phosphopeptides. During topical application of CPP-ACP complexes in the oral cavity, the CPP encounters the enamel pellicle consisting of salivary proteins and peptides. However the interactions of the CPP with the enamel salivary pellicle are not known. The studies presented here reveal that the predominant peptides of CPP-ACP complexes do interact with specific salivary proteins and peptides of the enamel pellicle, and provide a mechanism by which the CPP-ACP complexes are localised at the tooth surface to promote remineralisation.
Assuntos
Caseínas/farmacologia , Saliva/efeitos dos fármacos , Caseínas/efeitos adversos , Película Dentária/efeitos dos fármacos , Película Dentária/metabolismo , Humanos , Ligação Proteica , Saliva/metabolismo , Proteínas e Peptídeos Salivares/metabolismoRESUMO
OBJECTIVE: Methods currently used to triage patients from mass casualty events have a sparse evidence basis. The objective of this project was to assess gaps of the widely used Simple Triage and Rapid Transport (START) algorithm using a large database when it is used to triage low-acuity patients. Subsequently, we developed and tested evidenced-based improvements to START. METHODS: Using the National Trauma Database (NTDB), a large set of trauma victims were assigned START triage levels, which were then compared to recorded patient mortality outcomes using area under the receiver-operator curve (AUC). Subjects assigned to the "Minor/Green" level who nevertheless died prior to hospital discharge were considered mistriaged. Recursive partitioning identified factors associated with of these mistriaged patients. These factors were then used to develop candidate START models of improved triage, whose overall performance was then re-evaluated using data from the NTDB. This process of evaluating performance, identifying errors, and further adjusting candidate models was repeated iteratively. RESULTS: The study included 322,162 subjects assigned to "Minor/Green" of which 2,046 died before hospital discharge. Age was the primary predictor of under-triage by START. Candidate models which re-assigned patients from the "Minor/Green" triage level to the "Delayed/Yellow" triage level based on age (either for patients >60 or >75), reduced mortality in the "Minor/Green" group from 0.6% to 0.1% and 0.3%, respectively. These candidate START models also showed net improvement in the AUC for predicting mortality overall and in select subgroups. CONCLUSION: In this research model using trauma registry data, most START under-triage errors occurred in elderly patients. Overall START accuracy was improved by placing elderly but otherwise minimally injured-mass casualty victims into a higher risk triage level. Alternatively, such patients would be candidates for closer monitoring at the scene or expedited transport ahead of other, younger "Minor/Green" victims.
Assuntos
Incidentes com Feridos em Massa , Triagem/métodos , Adulto , Idoso , Algoritmos , Área Sob a Curva , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
Exertional heat stroke incidence is on the rise and has become the third leading cause of death in high school athletes. It is entirely preventable, yet this is a case of a 15-year-old, 97-kg male football player who presented unresponsive and hyperthermic after an August football practice. His blood pressure was 80/30, and his pulse was 180. He had a rectal temperature of 107.3°F, and upon entering the emergency department, he was rapidly cooled in 40 minutes. As he progressed, he developed metabolic acidosis, elevated liver enzymes, a prolapsed mitral valve with elevated troponin levels, and worsening hypotension even with extracorporeal membrane oxygenation support. After 3 days in the hospital, this young man was pronounced dead as a result of complications from exertional heat stroke. We address not only the complications of his hospital course relative to his positive blood cultures but also the complications that can result from attention-deficit/hyperactivity disorder medication our patient was taking. As the population of young adults becomes more obese and more highly medicated for attention-deficit/hyperactivity disorder, we sought out these growing trends in correlation with the increase in incidence of heat-related illness. We also address the predisposing factors that make young high school athletes more likely to experience heat illness and propose further steps to educate this susceptible population.
Assuntos
Futebol Americano , Golpe de Calor/etiologia , Adolescente , Anfetaminas/urina , Ansiolíticos/urina , Benzodiazepinas/urina , Transfusão de Sangue , Evolução Fatal , Golpe de Calor/diagnóstico , Golpe de Calor/terapia , Humanos , Masculino , Midazolam/urinaRESUMO
OBJECTIVE: The objective of this study was to compare the duration of analgesia, need for analgesic medications, and pain-related nursing interventions in patients who did and did not receive ultrasound-guided femoral nerve blocks for femur fracture pain. METHODS: This is a retrospective, preimplementation and postimplementation cohort study. An emergency department log of patients receiving femoral nerve blocks for femur fracture pain was compared with a similar cohort of patients with femur fractures who did not receive nerve blocks. The primary outcome is time from initial pain treatment until the next dose of analgesic. Data were analyzed using Kaplan-Meier methods. Secondary outcomes include number of doses of pain medication, total amount of morphine given, and number of pain-related nursing interventions. Data were analyzed with the Mann-Whitney U test. RESULTS: Eighty-one patients met inclusion/exclusion criteria: 50 in the preimplementation cohort and 31 in the postimplementation group. The median times until next dose of analgesic medication were 2.2 hours (interquartile range [IQR], 1.2-3.4 hours) in the preimplementation group and 6.1 hours (IQR, 3.8-9.5 hours) in the postimplementation group (P < 0.001). The median numbers of doses of pain medication were 0.3 per hour (IQR, 0.25-0.5 per hour) in the preimplementation group and 0.15 per hour (IQR, 0.07-0.3 per hour) in the postimplementation group. The median total doses of morphine were 14.8 µg/kg per hour (IQR, 9.4-19.2 µg/kg per hour) in the preimplementation group and 6.5 µg/kg per hour (IQR, 0-12.2 µg/kg per hour) in the postimplementation group (P = 0.01). The median numbers of nursing interventions were 0.4 per hour (IQR, 0.25-0.5 per hour) in the preimplementation group and 0.15 per hour (IQR, 0.1-0.2 per hour) in the postimplementation group (P < 0.001). CONCLUSIONS: Patients who received ultrasound-guided femoral nerve block for femur fracture pain had longer duration of analgesia, required fewer doses of analgesic medications, and needed fewer nursing interventions than those receiving systemic analgesic medication alone.
Assuntos
Analgesia/métodos , Analgésicos/uso terapêutico , Serviço Hospitalar de Emergência , Fraturas do Fêmur/terapia , Nervo Femoral , Bloqueio Nervoso/métodos , Dor/tratamento farmacológico , Ultrassonografia de Intervenção , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Manejo da Dor/métodos , Medição da Dor , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Recent studies reviewing immune mechanisms of immune thrombocytopenia (ITP) have suggested acute and chronic forms may represent distinct immunopathological disorders. This study evaluated absolute lymphocyte counts (ALCs) as predictors for ITP outcomes. PROCEDURE: CBCs with differential counts were ascertained at presentation, 3, 6, and 12 months for 204 patients. Receiver operating characteristic (ROC) curves were used to determine cutoff values. Logistic regression models and recursive partitioning were used to evaluate which variables were significantly associated with outcomes. RESULTS: ALC values at presentation were not independently predictive of disease duration. However, ALC values at 3 months were significant predictors. Sixty-eight percent (40/59) of patients >8 years of age and 43% (20/46) of patients ≤ 8 years who had an ALC ≤ 3,000/µl at 3 months developed chronic ITP. This compares to chronic rates of only 25% (3/12) and 2% (2/87) of patients >8 and ≤ 8 years, respectively, with an ALC > 3,000/µl at 3 months. Further, 92% (60/65) of patients who developed chronic ITP had a 3-month ALC ≤ 3,000/µl. An ALC > 3,000/µl at 3 months is a strong predictor for platelet recovery as only 5% (5/99) of these patients developed chronic ITP. CONCLUSION: This study suggests progression to lower lymphocyte counts over the first few months of disease is a strong predictor for chronic ITP, allowing for risk stratification of patients, particularly when used in conjunction with other known predictors. Further research is needed to confirm these findings and to fully investigate the pathophysiological mechanisms responsible for this association.
Assuntos
Contagem de Linfócitos , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
STUDY OBJECTIVE: A variety of methods have been proposed and used in disaster triage situations, but there is little more than expert opinion to support most of them. Anecdotal disaster experiences often report mediocre real-world triage accuracy. The study objective was to determine the accuracy of several disaster triage methods when predicting clinically important outcomes in a large cohort of trauma victims. METHODS: Pediatric, adult, and geriatric trauma victims from the National Trauma Data Bank were assigned triage levels, using each of 6 disaster triage methods: simple triage and rapid treatment (START), Fire Department of New York (FDNY), CareFlight, Glasgow Coma Scale (GCS), Sacco Score, and Unadjusted Sacco Score. Methods for approximating triage systems were vetted by subject matter experts. Triage assignments were compared against patient mortality at hospital discharge with area under the receiver operator curve. Secondary outcomes included death in the emergency department, use of a ventilator, and lengths of stay. Subgroup analysis assessed triage accuracy in patients by age, trauma type, and sex. RESULTS: In this study, 530,695 records were included. The Sacco Score predicted mortality most accurately, with area under the receiver operator curve of 0.883 (95% confidence interval 0.880 to 0.885), and performed well in most subgroups. FDNY was more accurate than START for adults but less accurate for children. CareFlight was best for burn victims, with area under the receiver operator curve of 0.87 (95% confidence interval 0.85 to 0.89) but mistriaged more salvageable trauma patients to "dead/black" (41% survived) than did other disaster triage methods (≈10% survived). CONCLUSION: Among 6 disaster triage methods compared against actual outcomes in trauma registry patients, the Sacco Score predicted mortality most accurately. This analysis highlighted comparative strengths and weakness of START, FDNY, CareFlight, and Sacco, suggesting areas in which each might be improved. The GCS predicted outcomes similarly to dedicated disaster triage strategies.
Assuntos
Medicina de Desastres/métodos , Triagem/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Desastres/estatística & dados numéricos , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Incidentes com Feridos em Massa/mortalidade , Incidentes com Feridos em Massa/estatística & dados numéricos , Pessoa de Meia-Idade , Curva ROC , Sistema de Registros , Estudos Retrospectivos , Ferimentos e Lesões/mortalidade , Adulto JovemRESUMO
OBJECTIVE: The objective of this study was to determine the predictive value of the Glasgow coma scale (GCS) and the Glasgow motor component (GMC) for overall mortality, death on arrival, and major injury and the relationship between GCS and length of stay (LOS) in the emergency department (ED) and hospital. METHODS: Records from the American College of Surgeons National Trauma Data Base from 2007 to 2009 were extracted. Patients 0 to 18 years old transported from a trauma scene with complete initial scene data were included. Statistical analysis, including construction of receiver-operator curves, determined the correlation between GCS, GMC, and the clinical outcomes of interest. RESULTS: There were 104,035 records with complete data for analysis, including 3946 deaths. Mean patient age was 12.6 (SD, 5.5) years. Glasgow coma scale was predictive of overall mortality, with area under the receiver-operator curve (AUC) of 0.946 (95% confidence interval [CI], 0.941-0.951); death on arrival, with AUC of 0.958 (95% CI, 0.953-0.963); and risk of major injury, with AUC of 0.720 (0.715-0.724). Lower GCS scores were associated with shorter ED LOS and longer hospital stays (P <0.001, analysis of variance) except GCS 3, associated with shorter hospitalizations. For predicting overall mortality, the AUC for GMC was 0.940 (95% CI, 0.935-0.945), and for predicting major injury, the AUC was 0.681 (95% CI, 0.677-0.686). CONCLUSIONS: For pediatric trauma victims, the GCS is predictive of mortality and injury outcomes, as well as both ED and hospital LOS, and has excellent prognostic accuracy. The GMC has predictive value for injury and mortality that is nearly equivalent to the full GCS.
Assuntos
Serviço Hospitalar de Emergência/organização & administração , Escala de Coma de Glasgow , Ferimentos e Lesões/mortalidade , Adolescente , Análise de Variância , Área Sob a Curva , Criança , Pré-Escolar , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Valor Preditivo dos Testes , Curva ROC , Sistema de Registros , Estados UnidosRESUMO
The Arg-specific gingipains of Porphyromonas gingivalis RgpA and RgpB have 97% identical sequences in their catalytic domains yet their propeptides are only 76% identical. RgpA isolates as a proteinase-adhesin complex (HRgpA) which hinders direct kinetic comparison of RgpAcat as a monomer with monomeric RgpB. We tested modifications of rgpA identifying a variant that enabled us to isolate histidine-tagged monomeric RgpA (rRgpAH). Kinetic comparisons between rRgpAH and RgpB used benzoyl-L-Arg-4-nitroanilide with and without cysteine and glycylglycine acceptor molecules. With no glycylglycine, values of Km, Vmax, kcat and kcat/Km for each enzyme were similar, but with glycylglycine Km decreased, Vmax increased and kcat increased ~ twofold for RgpB but ~ sixfold for rRgpAH. The kcat/Km for rRgpAH was unchanged whereas that of RgpB more than halved. Recombinant RgpA propeptide inhibited rRgpAH and RgpB with Ki 13 nM and 15 nM Ki respectively slightly more effectively than RgpB propeptide which inhibited rRgpAH and RgpB with Ki 22 nM and 29 nM respectively (p < 0.0001); a result that may be attributable to the divergent propeptide sequences. Overall, the data for rRgpAH reflected observations previously made by others using HRgpA, indicating rRgpAH fidelity and confirming the first production and isolation of functional affinity tagged RgpA.
Assuntos
Cisteína Endopeptidases , Peptídeo Hidrolases , Cisteína Endopeptidases Gingipaínas , Cisteína Endopeptidases/metabolismo , Adesinas Bacterianas/química , Domínio Catalítico , Porphyromonas gingivalis/metabolismo , Hemaglutininas/químicaRESUMO
Protein substrates of a novel secretion system of Porphyromonas gingivalis contain a conserved C-terminal domain (CTD) essential for secretion and attachment to the cell surface. Inactivation of lptO (PG0027) or porT produced mutants that lacked surface protease activity and an electron-dense surface layer. Both mutants showed co-accumulation of A-LPS and unmodified CTD proteins in the periplasm. Lipid profiling by mass spectrometry showed the presence of both tetra- and penta-acylated forms of mono-phosphorylated lipid A in the wild-type and porT mutant, while only the penta-acylated forms of mono-phosphorylated lipid A were found in the lptO mutant, indicating a specific role of LptO in the O-deacylation of mono-phosphorylated lipid A. Increased levels of non-phosphorylated lipid A and the presence of novel phospholipids in the lptO mutant were also observed that may compensate for the missing mono-phosphorylated tetra-acylated lipid A in the outer membrane (OM). Molecular modelling predicted LptO to adopt a ß-barrel structure characteristic of an OM protein, supported by the enrichment of LptO in OM vesicles. The results suggest that LPS deacylation by LptO is linked to the co-ordinated secretion of A-LPS and CTD proteins by a novel secretion and attachment system to form a structured surface layer.
Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Lipopolissacarídeos/metabolismo , Porphyromonas gingivalis/metabolismo , Acilação , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Lipopolissacarídeos/química , Periplasma/química , Periplasma/genética , Periplasma/metabolismo , Porphyromonas gingivalis/química , Porphyromonas gingivalis/genética , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
Porphyromonas gingivalis is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of P. gingivalis are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-binding glycoprotein found in saliva and gingival crevicular fluid, is believed to play an important role in innate immunity. In this study, bovine milk LF displayed proteinase inhibitory activity against P. gingivalis whole cells, significantly inhibiting both Arg- and Lys-specific proteolytic activities. LF inhibited the Arg-specific activity of purified RgpB, which lacks adhesin domains, and also inhibited the same activity of the RgpA/Kgp proteinase-adhesin complexes in a time-dependent manner, with a first-order inactivation rate constant (k(inact)) of 0.023 min(-1) and an inhibitor affinity constant (K(I)) of 5.02 µM. LF inhibited P. gingivalis biofilm formation by >80% at concentrations above 0.625 µM. LF was relatively resistant to hydrolysis by P. gingivalis cells but was cleaved into two major polypeptides (53 and 33 kDa) at R(284) to S(285), as determined by in-source decay mass spectrometry; however, these polypeptides remained associated with each other and retained inhibitory activity. The biofilm inhibitory activity of LF against P. gingivalis was not attributed to direct antibacterial activity, as LF displayed little growth inhibitory activity against planktonic cells. As the known RgpA/B and Kgp inhibitor N-α-p-tosyl-l-lysine chloromethylketone also inhibited P. gingivalis biofilm formation, the antibiofilm effect of LF may at least in part be attributable to its antiproteinase activity.
Assuntos
Adesinas Bacterianas/metabolismo , Biofilmes/efeitos dos fármacos , Cisteína Endopeptidases/metabolismo , Lactoferrina/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Biofilmes/crescimento & desenvolvimento , Bovinos , Cisteína Endopeptidases Gingipaínas , Líquido do Sulco Gengival/imunologia , Líquido do Sulco Gengival/metabolismo , Cinética , Espectrometria de Massas , Modelos Moleculares , Dados de Sequência Molecular , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/crescimento & desenvolvimento , Ligação Proteica , Saliva/imunologia , Saliva/metabolismoRESUMO
INTRODUCTION: Though many mass-casualty triage methods have been proposed, few have been validated in an evidence-based manner. The Sacco Triage Method (STM) has been shown to accurately stratify adult victims of blunt and penetrating trauma into groups of increasing mortality risk. However, it has not been validated for pediatric trauma victims. PURPOSE: Evaluate the STM's performance in pediatric trauma victims. METHODS: Records from the United States' National Trauma Data Base, a registry of trauma victims developed by the American College of Surgeons, were extracted for the 2007-2009 reporting years. Patients ≤ 18 years of age transported from a trauma scene with complete initial scene data were included in the analysis. Sacco triage scores were assigned to each registry patient, and receiver-operator curves were developed for predicting mortality, along with several secondary outcomes. Area under the receiver-operator curve (AUC) was the main outcome statistic. Sensitivity analysis was performed using a Sacco score without age adjustment, using blunt versus penetrating trauma, and using patients <12 years of age. RESULTS: There were 210,175 pediatric records, of which 90,037 had complete data for analysis. The STM with age adjustment predicted pediatric trauma mortality with an AUC of 0.933 (95% CI: 0.925-0.940). Without the age adjustment term, it predicted mortality with an AUC of 0.924 (95% CI: 0.916-0.933). The STM with age adjustment predicted blunt trauma mortality in 72,467 patients with an AUC of 0.938 (95% CI: 0.929-0.947) and penetrating trauma mortality in 10,099 patients with an AUC of 0.927 (95% CI: 0.911-0.943). These findings did not change significantly when analysis was limited to patients <12 years of age. The Sacco Triage Method was also predictive of some secondary outcomes, such as major injury and death on arrival to the emergency department. CONCLUSION: The Sacco Triage Method, with or without its age adjustment term, was a highly accurate predictor of mortality in pediatric trauma patients in this registry database. This triage method appears to be a valid strategy for the prioritization of injured children.
Assuntos
Serviços Médicos de Emergência/organização & administração , Pediatria/métodos , Triagem/métodos , Ferimentos e Lesões/classificação , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Medicina Baseada em Evidências , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Curva ROC , Sistema de Registros , Índices de Gravidade do Trauma , Estados Unidos/epidemiologia , Ferimentos e Lesões/epidemiologiaRESUMO
Porphyromonas gingivalis is a major pathogen associated with chronic periodontitis, an inflammatory disease of the supporting tissues of the teeth. The Arg-specific (RgpA/B) and Lys-specific (Kgp) cysteine proteinases of P. gingivalis are major virulence factors for the bacterium. In this study κ-casein(109-137) was identified in a chymosin digest of casein as an inhibiting peptide of the P. gingivalis proteinases. The peptide was synthesized and shown to inhibit proteolytic activity associated with P. gingivalis whole cells, purified RgpA-Kgp proteinase-adhesin complexes, and purified RgpB proteinase. The peptide κ-casein(109-137) exhibited synergism with Zn(II) against both Arg- and Lys-specific proteinases. The active region for inhibition was identified as κ-casein(117-137) using synthetic peptides. Kinetic studies revealed that κ-casein(109-137) inhibits in an uncompetitive manner. A molecular model based on the uncompetitive action and its synergistic ability with Zn(II) was developed to explain the mechanism of inhibition. Preincubation of P. gingivalis with κ-casein(109-137) significantly reduced lesion development in a murine model of infection.