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1.
Simul Healthc ; 19(1S): S90-S97, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37651101

RESUMO

ABSTRACT: With the increasing availability of virtual reality (VR) and its lower overall costs of use, the objective of this review was to compare VR to traditional simulation in terms of learning outcomes. Studies were included if they met the following criteria: ( a ) research study (of any design), ( b ) focused on learners in health professions, and ( c ) compared VR with traditional simulation. Studies were excluded for the following reasons: ( a ) not a research study, ( b ) focused on learners outside health professions, ( c ) used screen-based or computer-based simulation, ( d ) used a task trainer, and ( e ) did not involve a comparison of VR to traditional simulation. The searches were run on November 11 and 12, 2021, in CINAHL via EBSCO, Ovid Embase, ERIC via EBSCO, IEEE Xplore, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science Core Collection. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guided the review. A team of researchers applied Kirkpatrick's Levels, Melnyk's Levels of Evidence, and Critical Appraisal Skills Programme guidelines to assess the level of evidence and look for bias. Fifteen studies were reviewed including 11 randomized controlled trials. The lead researcher synthesized the study results into 3 categories: (1) traditional simulation performed better, (2) VR performed better, and (3) comparable outcomes. There is insufficient evidence to endorse one form of simulation (VR or traditional) as more effective at this time. The body of evidence contained too few studies to draw meaningful conclusions to answer the guiding question. The studies covered a large range of modalities, learner groups, and healthcare topics, preventing a meta-analysis. Based on the literature and experience, we recommend that VR experiences be proctored, include debriefing, have a backup plan for cybersickness or myopia, and have time and costs documented. Use of VR is likely to expand; thus, research is needed to inform the best contexts and applications.


Assuntos
Simulação por Computador , Realidade Virtual , Humanos , Competência Clínica , Ocupações em Saúde , Aprendizagem
2.
Simul Healthc ; 16(4): 268-274, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32890319

RESUMO

SUMMARY STATEMENT: Despite the significant role that stress plays in clinical care and education and the potential benefit of virtual reality (VR) as a simulation modality, there is a dearth of literature on stress and VR. The results of this scoping review have shown the positive effect that VR simulation can have on mitigating the negative aspects of stress during simulation and clinical training as well as improving provider performance and affect. Virtual reality technology, and immersive VR specifically, has the potential to powerfully transform how simulation education is being conducted. Because of this, the authors encourage researchers to put more focus into this topic and in determining how VR can be used to provide simulations with excellent training and a strong sense of presence for the purpose of addressing how stress can impact learners' clinical training and performance.


Assuntos
Treinamento por Simulação , Realidade Virtual , Simulação por Computador , Pessoal de Saúde , Humanos
3.
Inflamm Bowel Dis ; 25(8): 1408-1416, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30861068

RESUMO

BACKGROUND AND AIMS: Cross-sectional studies on sexual function in men with inflammatory bowel disease (IBD) yield mixed results. Using a prospective incidence cohort, we aimed to describe sexual function at baseline and over time and to identify factors associated with impaired sexual function in men with IBD. METHODS: Men 18 years and older enrolled between April 2008 and January 2013 in the Ocean State Crohn's and Colitis Area Registry (OSCCAR) with a minimum of 2 years of follow-up were eligible for study. Male sexual function was assessed using the International Index of Erectile Function (IIEF), a self-administered questionnaire that assesses 5 dimensions of sexual function over the most recent 4 weeks. To assess changes in the IIEF per various demographic and clinical factors, linear mixed effects models were used. RESULTS: Sixty-nine of 82 eligible men (84%) completed the questionnaire (41 Crohn's disease, 28 ulcerative colitis). The mean age (SD) of the cohort at diagnosis was 43.4 (19.2) years. At baseline, 39% of men had global sexual dysfunction, and 94% had erectile dysfunction. Independent factors associated with erectile dysfunction are older age and lower physical and mental component summary scores on the Short Form Health Survey (SF-36). CONCLUSION: In an incident cohort of IBD patients, most men had erectile dysfunction. Physicians should be aware of the high prevalence of erectile dysfunction and its associated risk factors among men with newly diagnosed IBD to direct multidisciplinary treatment planning.


Assuntos
Disfunção Erétil/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Qualidade de Vida , Índice de Gravidade de Doença , Disfunções Sexuais Fisiológicas/epidemiologia , Adolescente , Adulto , Idoso , Disfunção Erétil/etiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Disfunções Sexuais Fisiológicas/etiologia , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto Jovem
4.
Osteoporos Int ; 29(6): 1359-1366, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29520605

RESUMO

Bone disease is prevalent among patients with inflammatory bowel disease (IBD), though bone density screening remains underutilized. We used CT scans performed for other indications in IBD patients to identify and monitor osteopenia using CT attenuation values at the lumbar spine. Significant rates of bone disease were detected which would have otherwise gone undiagnosed. INTRODUCTION: Osteoporosis affects about 14-42% of patients with IBD. Though screening is recommended in IBD patients with risk factors, it remains underutilized. In patients with newly diagnosed IBD, we used CT scans performed for other indications to identify and monitor progression of osteopenia. METHODS: Using the Ocean State Crohn's and Colitis Area Registry, we identified adult patients with one or more abdominal CT scans. Each patient had two age- and gender-matched controls. Radiologists measured attenuation through trabecular bone in the L1 vertebral body recorded in Hounsfield units (HU). Generalized estimating equations were used to measure how HU varied as a function of gender, type of IBD, and age. RESULTS: One hundred five IBD patients were included, and 72.4% were classified as "normal" bone mineral density (BMD) and 27.6% as potentially osteopenic: 8.6% with ulcerative colitis and 19.0% with Crohn's disease. We found a decrease in bone density over time (p < 0.001) and that BMD decreases more in Crohn's disease than in ulcerative colitis (p < 0.004). Sixty patients had two CT scans, and mean loss of 9.3 HU was noted. There was a non-significant decrease in BMD over time in patients exposed to > 31 days of steroids and BMD was stable with < 30 days of steroid exposure (p < 0.09). CONCLUSION: Using CT scans obtained for other indications, we found low rates of osteopenia and osteoporosis that may otherwise have gone undiagnosed. Refinement of opportunistic screening may have advantages in terms of cost-savings and earlier detection of bone loss.


Assuntos
Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Diagnóstico Precoce , Feminino , Seguimentos , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Humanos , Incidência , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Vértebras Lombares/fisiopatologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Sistema de Registros , Rhode Island/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
5.
Cogn Psychol ; 86: 62-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26896879

RESUMO

Although we live in a complex and multi-causal world, learners often lack sufficient data and/or cognitive resources to acquire a fully veridical causal model. The general goal of making precise predictions with energy-efficient representations suggests a generic prior favoring causal models that include a relatively small number of strong causes. Such "sparse and strong" priors make it possible to quickly identify the most potent individual causes, relegating weaker causes to secondary status or eliminating them from consideration altogether. Sparse-and-strong priors predict that competition will be observed between candidate causes of the same polarity (i.e., generative or else preventive) even if they occur independently. For instance, the strength of a moderately strong cause should be underestimated when an uncorrelated strong cause also occurs in the general learning environment, relative to when a weaker cause also occurs. We report three experiments investigating whether independently-occurring causes (either generative or preventive) compete when people make judgments of causal strength. Cue competition was indeed observed for both generative and preventive causes. The data were used to assess alternative computational models of human learning in complex multi-causal situations.


Assuntos
Aprendizagem por Associação , Comportamento Competitivo , Formação de Conceito , Sinais (Psicologia) , Julgamento , Teorema de Bayes , Feminino , Humanos , Modelos Lineares , Masculino , Modelos Psicológicos , Adulto Jovem
6.
Aliment Pharmacol Ther ; 39(8): 811-22, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24612278

RESUMO

BACKGROUND: Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC). Data on fatigue in newly diagnosed patients are unavailable. AIM: To report prevalence of fatigue in newly diagnosed CD and UC patients and examine its association with health-related quality of life (HRQOL), depression and disability. METHODS: The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is a statewide cohort of newly diagnosed inflammatory bowel disease patients in Rhode Island. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were administered instruments measuring HRQOL, overall disability and work impairment, and depression. RESULTS: Fatigue was prevalent in 26.4% of 220 subjects. Cohen's d effect sizes for fatigue were large: Short-Form 36 Health Survey mental health component (CD 1.5, UC 1.4) and physical health component (CD 1.4, UC 1.4), EuroQol-5D valuation of current health state (CD 1.2, UC 1.0), Inflammatory Bowel Disease Questionnaire (CD 1.9, UC 1.6) and Patient Health Questionnaire depression scale (CD 1.8, UC 1.7). Fatigued patients reported more work impairment (Score difference: CD 29.5%, UC 23.8%) and activity impairment (score difference: CD 32.3%, UC 25.7%) on the Work Productivity and Activity Impairment Questionnaire. Fatigue's association with all scores remained highly significant despite controlling for disease activity. CONCLUSIONS: Fatigue is strongly associated with poor HRQOL, disability and depression similarly in CD and UC even when controlling for disease activity. Fatigue's association with a wide range of patient-reported outcome measures suggests that monitoring fatigue is a simple way to screen for overall disruption in patient life.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Fadiga/etiologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Estudos de Coortes , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Depressão , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Avaliação da Deficiência , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Sistema de Registros , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
7.
Scand J Med Sci Sports ; 17(3): 216-22, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16800843

RESUMO

The purpose of this study was to evaluate the effects of ankle bracing on rearfoot angular displacement and angular velocity during a sudden inversion movement. A 1 x 3 factorial design was used. The single independent variable was ankle brace condition with three levels: semi-rigid, lace-up and control. The two dependent variables were rearfoot average angular displacement and average angular velocity. Twenty-four healthy volunteers participated in this study. A motion analysis system was used to capture, model and calculate two-dimensional rearfoot motion while the subjects' ankle/foot complex was inverted to 35 degrees on a platform device. All subjects performed five trials of each ankle brace condition, and the average of these trials was used for statistical analysis. The semi-rigid brace significantly reduced rearfoot angular displacement and angular velocity compared with the lace-up (P<0.05) and control conditions (P<0.05). Additionally, the lace-up style brace demonstrated significantly less rearfoot angular displacement and angular velocity compared with the control condition (P<0.05). These results demonstrate that a semi-rigid ankle brace is more superior then a lace-up style brace in limiting rearfoot angular displacement and angular velocity. Moreover, the lace-up style brace offers significant restriction of these measures compared with no support.


Assuntos
Tornozelo/fisiologia , Braquetes , Movimento/fisiologia , Adulto , Humanos , Estados Unidos
8.
Transfus Clin Biol ; 13(1-2): 97-102, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16563828

RESUMO

The Escherichia coli ammonium transport protein (AmtB) has become the model system of choice for analysis of the process of ammonium uptake by the ubiquitous Amt family of inner membrane proteins. Over the past 6 years we have developed a range of genetic and biochemical tools in this system. These have allowed structure/function analysis to develop rapidly, offering insight initially into the membrane topology of the protein and most recently leading to the solution of high-resolution 3D structures. Genetic analysis has revealed a novel regulatory mechanism that is apparently conserved in prokaryotic Amt proteins and genetic approaches are also now being used to dissect structure/function relationships in Amt proteins. The now well-recognised homology between the Amt proteins, found in archaea, eubacteria, fungi and plants, and the Rhesus proteins, found characteristically in animals, also means that studies on E. coli AmtB can potentially shed light on structure/function relationships in the clinically important Rh proteins.


Assuntos
Proteínas de Transporte de Cátions/fisiologia , Proteínas de Escherichia coli/fisiologia , Compostos de Amônio Quaternário/metabolismo , Proteínas de Saccharomyces cerevisiae/fisiologia , Amônia/metabolismo , Transporte Biológico , Proteínas Sanguíneas/química , Proteínas Sanguíneas/fisiologia , Proteínas de Transporte de Cátions/química , Proteínas de Escherichia coli/química , Regulação da Expressão Gênica , Humanos , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/fisiologia , Modelos Moleculares , Nucleotidiltransferases/fisiologia , Proteínas PII Reguladoras de Nitrogênio/fisiologia , Conformação Proteica , Sistema do Grupo Sanguíneo Rh-Hr/química , Sistema do Grupo Sanguíneo Rh-Hr/fisiologia , Proteínas de Saccharomyces cerevisiae/química , Transdução de Sinais , Especificidade da Espécie , Relação Estrutura-Atividade , Especificidade por Substrato
9.
Biochem Soc Trans ; 33(Pt 1): 170-2, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15667297

RESUMO

Ammonium transport proteins belonging to the Amt family are ubiquitous in prokaryotes. In Escherichia coli, the AmtB protein and the associated P(II) signal transduction protein (GlnK) have recently been recognized as an ammonium sensory system that effectively couples the intracellular nitrogen regulation (Ntr) system to external changes in ammonium availability. Given the almost invariant coupling of AmtB and GlnK in bacteria and archaea it seems probable that these two proteins may constitute an ancestral nitrogen-responsive system that has been coupled with a variety of unrelated nitrogen regulatory processes, which are now found in prokaryotes. The multiplicity of P(II) proteins could therefore be considered to have evolved from an ancestral GlnK-like protein and to have subsequently been adapted to control many other aspects of nitrogen metabolism.


Assuntos
Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Escherichia coli/metabolismo , Nitrogênio/metabolismo , Óperon
10.
Int J Sports Med ; 25(1): 73-7, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14750017

RESUMO

Athletic trainers typically use therapeutic ultrasound to treat skeletal muscle contusion injuries. However, the structural outcomes underlying this treatment are not well understood. Our working hypothesis was that following a blunt contusion injury to the gastrocnemius muscle, ultrasound treatment would facilitate recovery, as indicated by changes in several biological markers of skeletal muscle regeneration. Eighty male Wistar rats (three-month) were studied. Following anesthetic administration, each animal received a bilateral contusion injury to the gastrocnemius muscle. Pulsed ultrasound treatment was subsequently initiated six hours post-contusion injury unilaterally on the right gastrocnemius muscle, and ultrasound treatment was continued once daily for seven days. The left (non-ultrasound treated) and right (ultrasound treated) gastrocnemius muscles of 10 animals per group were excised at 1-, 3-, 5-, 7-, 14-, 21-, 28-, and 40-days post-contusion injury. There were no differences in muscle mass, total protein concentration, or fiber cross-sectional area between the right and left gastrocnemius muscles at any post-injury time point examined. Further, when fiber cross-sectional area was normalized to muscle mass, there were no differences. Myonuclear number and cross-sectional area per myonuclei between the right and left gastrocnemius muscles were not different. These results suggest that ultrasound, as administered, does not hasten or improve the regeneration of skeletal muscle following contusion injury.


Assuntos
Contusões/patologia , Músculo Esquelético/lesões , Músculo Esquelético/fisiologia , Terapia por Ultrassom , Animais , Traumatismos em Atletas/reabilitação , Masculino , Fibras Musculares Esqueléticas/patologia , Proteínas/análise , Ratos , Ratos Wistar
11.
Ear Nose Throat J ; 80(8): 536, 539-40, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11523471

RESUMO

We evaluated the intrasession and intersession reliability of acoustic rhinometry in measuring nasal cross-sectional areas in 10 subjects. Subjects were measured under three conditions: with a Breathe Right nasal strip in place, with a sham strip in place, and with no strip in place. Two sets of three measurements were taken 1 week apart. The intrasession reliability both with and without the Breathe Right strip was very good (intraclass correlation coefficient [ICC] [2,1]: 0.97 and 0.98, respectively). The intersession reliability with and without the Breathe Right strip was not nearly as good (ICC [2,1]: 0.62 and 0.67). The Breathe Right strip increased the mean nasal cross-sectional area by 0.10 cm2 (17.4%). We conclude that acoustic rhinometry is a reliable way to measure nasal cross-sectional area during a single session of multiple tests, but it is not as reliable across sessions. We also determined that the Breathe Right nasal strip significantly increases nasal cross-sectional area.


Assuntos
Manometria/métodos , Cavidade Nasal/fisiologia , Respiração , Acústica , Humanos , Mucosa Nasal/fisiologia , Otolaringologia/instrumentação , Reprodutibilidade dos Testes
12.
Arch Phys Med Rehabil ; 82(6): 845-50, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11387593

RESUMO

OBJECTIVE: To describe the relationships among muscle temperature, skin temperature, room temperature, body core temperature, time, and subcutaneous adipose thickness during cryotherapy and rewarming. DESIGN: A multiple linear regression with 5 independent variables (skin temperature, body core temperature, subcutaneous adipose thickness, room temperature, time) predicting intramuscular (IM) temperature. SETTING: A sports injury research laboratory. PARTICIPANTS: Fifteen volunteers with thigh skinfold measurements smaller than 40 mm. INTERVENTIONS: Thirty-minute cryotherapy treatment (ice bag) followed by a 120-minute rewarming period. MAIN OUTCOME MEASURES: The relationship between skin and IM temperature was described, and an equation predicting IM temperature by using room temperature, skin temperature, body core temperature, time, and adipose thickness was developed. RESULTS: Pearson's correlations between each predictor variable of IM temperature during cryotherapy were skin temperature, r = .46; skinfold, r = .37; time, r = -.59; core temperature, r =.21; and room temperature, r = -.47. During rewarming, the correlations were skin temperature, r = .71; skinfold, r = .27; time, r = .76; core temperature, r = - .05; and room temperature, r = - .21. A multiple regression equation (R(2) = .76) was developed to predict IM temperature during cryotherapy. A separate equation (R(2) =.81) was developed to predict muscle temperatures during rewarming. CONCLUSIONS: During and after ice application, no single predictor adequately explained the change in IM temperature. Skin surface temperature was a weak predictor of IM temperature during cryotherapy and should not be used as the sole dependent measure in cryotherapy efficacy studies.


Assuntos
Temperatura Corporal , Crioterapia , Músculos/fisiologia , Dobras Cutâneas , Adulto , Crioterapia/métodos , Humanos , Análise Multivariada , Análise de Regressão , Temperatura Cutânea , Temperatura , Fatores de Tempo
13.
Microbiol Mol Biol Rev ; 65(1): 80-105, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11238986

RESUMO

The P(II) family of signal transduction proteins are among the most widely distributed signal proteins in the bacterial world. First identified in 1969 as a component of the glutamine synthetase regulatory apparatus, P(II) proteins have since been recognized as playing a pivotal role in control of prokaryotic nitrogen metabolism. More recently, members of the family have been found in higher plants, where they also potentially play a role in nitrogen control. The P(II) proteins can function in the regulation of both gene transcription, by modulating the activity of regulatory proteins, and the catalytic activity of enzymes involved in nitrogen metabolism. There is also emerging evidence that they may regulate the activity of proteins required for transport of nitrogen compounds into the cell. In this review we discuss the history of the P(II) proteins, their structures and biochemistry, and their distribution and functions in prokaryotes. We survey data emerging from bacterial genome sequences and consider other likely or potential targets for control by P(II) proteins.


Assuntos
Bactérias/genética , Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Nitrogênio/metabolismo , Transdução de Sinais , Proteínas de Bactérias/genética , Transporte Biológico , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Cianobactérias/química , Cianobactérias/genética , Cianobactérias/metabolismo , Glutamato-Amônia Ligase/metabolismo , Proteínas PII Reguladoras de Nitrogênio , Fosforilação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteobactérias/química , Proteobactérias/genética , Proteobactérias/metabolismo , Relação Estrutura-Atividade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Mol Gen Genet ; 264(5): 555-64, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11212910

RESUMO

Symbiotic nitrogen fixation involves the development, on the legume plant root, of specialised organs called nodules, within which plant photosynthates are exchanged for combined nitrogen of bacterial origin. The glnB gene encodes a signal transduction protein (P(II)) which is a component of the bacterial nitrogen regulation (Ntr) system and an essential regulator of ammonium assimilation. We demonstrate that in Rhizobium leguminosarum the glnB promoter is strongly regulated by nitrogen and NtrC, but still shows a significant level of activity in conditions of nitrogen excess. Expression of genes involved in nitrogen assimilation has been shown to be absent in nitrogen-fixing bacteroids, and, in agreement with this, we find that the glnB promoter is down-regulated during bacteroid differentiation at a time coincident with the arrest of bacterial division in the nodule. This pattern is common to other bacterial genes involved in nitrogen assimilation and it is noteworthy that the zone where the glnB promoter is active is coincident with the region in which NtrC is expressed.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação para Baixo , Rhizobium leguminosarum/genética , Simbiose , Transativadores , Fatores de Transcrição , Sequência de Aminoácidos , Proteínas de Ligação a DNA/genética , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Dados de Sequência Molecular , Nitrogenase/metabolismo , Proteínas PII Reguladoras de Nitrogênio , Fenótipo , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Fatores de Tempo , beta-Galactosidase/metabolismo
15.
Crit Care Med ; 28(9): 3161-5, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11008975

RESUMO

OBJECTIVE: Esophagogastrectomy is an established surgical treatment for esophageal malignancy. The postoperative period may be complicated by the development of acute lung injury syndromes and thus, may provide a useful model in which to study the early pathogenic mechanisms of inflammatory lung injury. DESIGN: Open, prospective study. SETTING: High dependency and intensive therapy units. PATIENTS: Eight healthy male volunteers and 20 patients in the early postoperative period INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The lung protein accumulation index (PAI) of radiolabeled transferrin was determined by using a portable, double-isotope system. The following circulating inflammatory markers-thought to reflect neutrophil-endothelial activation and injury including circulating neutrophil elastase-soluble L-, E-, and P-selectins and thrombomodulin and von Willebrand factor antigen were assayed from venous blood samples The PAI for healthy volunteers was median -0.5 (range, -1.73 to 0.27) x 10(-3)/min and for patients undergoing esophagogastrectomy -0.005 (range, -1.53 to 2.28) x 10(-3)/min. There was no statistical difference between the two groups. In the postesophagogastrectomy group, a significant elevation in circulating levels of neutrophil elastase, soluble P- and E-selectin, thrombomodulin, and von Willebrand factor antigen were observed relative to the control group but only circulating plasma elastase demonstrated a significant correlation with the PAI (r2 = .23, p =.03). CONCLUSIONS: The data suggest patients undergoing esophagogastrectomy develop a inflammatory response but this is not a surrogate of permeability and other factors are likely to determine persistent injury to the alveolar-capillary barrier function in this patient group.


Assuntos
Permeabilidade Capilar/imunologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Gastrectomia , Neutrófilos/imunologia , Complicações Pós-Operatórias/imunologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Idoso , Feminino , Humanos , Elastase de Leucócito/sangue , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Valores de Referência , Síndrome do Desconforto Respiratório/diagnóstico , Selectinas/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Trombomodulina/sangue , Fator de von Willebrand/metabolismo
16.
Mol Microbiol ; 37(2): 331-44, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10931328

RESUMO

The Mep/Amt proteins constitute a new family of transport proteins that are ubiquitous in nature. Members from bacteria, yeast and plants have been identified experimentally as high-affinity ammonium transporters. We have determined the topology of AmtB, a Mep/Amt protein from Escherichia coli, as a representative protein for the complete family. This was established using a minimal set of AmtB-PhoA fusion proteins with a complementary set of AmtB-LacZ fusions. These data, accompanied by an in silico analysis, indicate that the majority of the Mep/Amt proteins contain 11 membrane-spanning helices, with the N-terminus on the exterior face of the membrane and the C-terminus on the interior. A small subset, including E. coli AmtB, probably have an additional twelfth membrane-spanning region at the N-terminus. Addition of PhoA or LacZ alpha-peptide to the C-terminus of E. coli AmtB resulted in complete loss of transport activity, as judged by measurements of [14C]-methylammonium uptake. This C-terminal region, along with four membrane-spanning helices, contains multiple residues that are conserved within the Mep/Amt protein family. Structural modelling of the E. coli AmtB protein suggests a number of secondary structural features that might contribute to function, including a putative ammonium binding site on the periplasmic face of the membrane at residue Asp-182. The implications of these results are discussed in relation to the structure and function of the related human Rhesus proteins.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transporte de Cátions , Proteínas de Escherichia coli , Escherichia coli/metabolismo , Proteínas de Membrana/metabolismo , Fosfatase Alcalina/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Transporte Biológico , Western Blotting , Proteínas de Transporte/química , Proteínas de Transporte/genética , Membrana Celular/fisiologia , Escherichia coli/química , Evolução Molecular , Genes Reporter , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Metilaminas/metabolismo , Modelos Biológicos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , beta-Galactosidase/genética
17.
Mol Microbiol ; 37(2): 443-52, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10931338

RESUMO

We report the identification of a previously unrecognized gene that is involved in the regulation of the Rhizobium leguminosarum glnII (glutamine synthetase II) gene. This gene, which is situated immediately upstream of glnII, was identified by means of a deletion/complementation analysis performed in the heterologous background of Klebsiella pneumoniae. It has been designated gstI (glutamine synthetase translational Inhibitor) because, when a complete version of gstI is present, it is possible to detect glnII-specific mRNA, but neither GSII activity nor GSII protein. The gstI gene encodes a small (63 amino acids) protein, which acts in cis or in trans with respect to glnII and is transcribed divergently with respect to glnII from a promoter that was found to be strongly repressed by the nitrogen transcriptional regulator NtrC. A mutated version of GstI lacking the last 14 amino acids completely lost its capacity to repress glnII expression. Our results indicate that gstI mediates the translation inhibition of glnII mRNA and, based on in silico analyses, a mechanism for GstI action is proposed.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Glutamato-Amônia Ligase/metabolismo , Proteínas Repressoras/genética , Rhizobium leguminosarum/genética , Fatores de Transcrição , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Proteínas de Ligação a DNA/metabolismo , Teste de Complementação Genética , Immunoblotting , Klebsiella pneumoniae/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Proteínas PII Reguladoras de Nitrogênio , Regiões Promotoras Genéticas , Biossíntese de Proteínas , RNA Mensageiro/análise , Proteínas Repressoras/metabolismo , Rhizobium leguminosarum/metabolismo , Transativadores/metabolismo
18.
J Biol Chem ; 275(49): 38452-6, 2000 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-10952972

RESUMO

X-ray crystallographic analysis of the Escherichia coli P(II) protein paralogues GlnB and GlnK has shown that they share a superimposable structural core but can differ in conformation of the T-loop, a region of the protein (residues 37-54) that has been shown to be important for interaction with other proteins. In Klebsiella pneumoniae GlnK has been shown to have a clearly defined function in regulating NifL-mediated inhibition of NifA activity in response to the nitrogen status, and GlnB, when expressed from the chromosome, does not substitute for GlnK. Because the T-loops of K. pneumoniae and E. coli GlnB and GlnK differ at just three residues, 43, 52, and 54, we have used a previously constructed heterologous system, in which K. pneumoniae nifLA is expressed in E. coli, to investigate the importance of GlnK residues 43, 52, and 54 for regulation of the NifLA interaction. By site-directed mutagenesis of glnB we have shown that residue 54 is the single most important amino acid in the T-loop in the context of the regulation of NifA activity. Furthermore, a combination of just two changes, in residues 54 and 43, allows GlnB to function as GlnK and completely relieve NifL inhibition of NifA activity.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Fixação de Nitrogênio/genética , Substituição de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Transporte/genética , Cristalografia por Raios X/métodos , Escherichia coli/genética , Genótipo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo
19.
Nucleic Acids Res ; 28(13): 2563-70, 2000 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-10871407

RESUMO

Bacterial RNA polymerase holoenzymes containing the sigma subunit sigma(N) (sigma(54)) can form a stable closed complex with promoter DNA but only undergo transition to an open complex and transcription initiation when acted on by an activator protein. Proteins of the sigma(N) family have a conserved N-terminal region of 50 amino acids (Region I) that is separated from a conserved C-terminal region of around 360 amino acids (Region III) by a much more variable sequence of between 30 and 110 residues (Region II). We have investigated the role of Region II in Klebsiella pneumoniae sigma(N) by studying the properties of deletions of all or part of the region both in vivo and in vitro. We found that whilst Region II is not essential, deletion of all or part of it can significantly impair sigma(N) activity. Deletions have effects on DNA binding by the isolated sigma factor and on holoenzyme formation, but the most marked effects are on transition of the holoenzyme from the closed to the open complex in the presence of the activator protein.


Assuntos
RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/metabolismo , Klebsiella pneumoniae/enzimologia , Fator sigma/química , Fator sigma/metabolismo , Sequência de Aminoácidos , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , RNA Polimerases Dirigidas por DNA/genética , Genes Bacterianos/genética , Genes Reporter/genética , Holoenzimas/química , Holoenzimas/genética , Holoenzimas/metabolismo , Klebsiella pneumoniae/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Oxirredutases/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA Polimerase Sigma 54 , Alinhamento de Sequência , Deleção de Sequência/genética , Fator sigma/genética , Relação Estrutura-Atividade , Transcrição Gênica/genética , Ativação Transcricional/genética
20.
Intensive Care Med ; 26(2): 202-5, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10784309

RESUMO

OBJECTIVE: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI). DESIGN: Prospective, interventional study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3-8). INTERVENTIONS: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if % CPP/%CVR < or = 2. RESULTS: Cerebral blood flow (CBF: Xe133 inhalation technique), jugular bulb oxygen saturation (SjO2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % (+/- 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 +/- 3 to 28 +/- 3 ml/ 100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO2 did not change significantly from baseline. TCD remained within the normal range. CONCLUSIONS: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/fisiopatologia , Circulação Cerebrovascular , Pressão Intracraniana/efeitos dos fármacos , Norepinefrina/uso terapêutico , Vasoconstritores/uso terapêutico , Adolescente , Adulto , Análise de Variância , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Lesões Encefálicas/metabolismo , Feminino , Escala de Coma de Glasgow , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Pressão Intracraniana/fisiologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Oxigênio/metabolismo , Estudos Prospectivos , Ultrassonografia Doppler Transcraniana , Vasoconstritores/administração & dosagem
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