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1.
Simul Healthc ; 19(1S): S90-S97, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37651101

ABSTRACT

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.


Subject(s)
Computer Simulation , Virtual Reality , Humans , Clinical Competence , Health Occupations , Learning
2.
Simul Healthc ; 16(4): 268-274, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-32890319

ABSTRACT

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.


Subject(s)
Simulation Training , Virtual Reality , Computer Simulation , Health Personnel , Humans
3.
Inflamm Bowel Dis ; 25(8): 1408-1416, 2019 07 17.
Article in English | MEDLINE | ID: mdl-30861068

ABSTRACT

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.


Subject(s)
Erectile Dysfunction/epidemiology , Inflammatory Bowel Diseases/complications , Quality of Life , Severity of Illness Index , Sexual Dysfunction, Physiological/epidemiology , Adolescent , Adult , Aged , Erectile Dysfunction/etiology , Follow-Up Studies , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Sexual Dysfunction, Physiological/etiology , Surveys and Questionnaires , United States/epidemiology , Young Adult
4.
Osteoporos Int ; 29(6): 1359-1366, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29520605

ABSTRACT

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.


Subject(s)
Bone Diseases, Metabolic/diagnostic imaging , Inflammatory Bowel Diseases/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Bone Density/drug effects , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/physiopathology , Early Diagnosis , Female , Follow-Up Studies , Glucocorticoids/adverse effects , Glucocorticoids/pharmacology , Humans , Incidence , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Lumbar Vertebrae/physiopathology , Male , Mass Screening/methods , Middle Aged , Registries , Rhode Island/epidemiology , Tomography, X-Ray Computed/methods , Young Adult
5.
Cogn Psychol ; 86: 62-86, 2016 May.
Article in English | MEDLINE | ID: mdl-26896879

ABSTRACT

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.


Subject(s)
Association Learning , Competitive Behavior , Concept Formation , Cues , Judgment , Bayes Theorem , Female , Humans , Linear Models , Male , Models, Psychological , Young Adult
6.
Aliment Pharmacol Ther ; 39(8): 811-22, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24612278

ABSTRACT

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.


Subject(s)
Colitis, Ulcerative/complications , Crohn Disease/complications , Fatigue/etiology , Quality of Life , Adolescent , Adult , Aged , Cohort Studies , Colitis, Ulcerative/physiopathology , Crohn Disease/physiopathology , Depression , Depressive Disorder/epidemiology , Depressive Disorder/etiology , Disability Evaluation , Fatigue/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Psychiatric Status Rating Scales , Registries , Severity of Illness Index , Surveys and Questionnaires , Young Adult
7.
Scand J Med Sci Sports ; 17(3): 216-22, 2007 Jun.
Article in English | MEDLINE | ID: mdl-16800843

ABSTRACT

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.


Subject(s)
Ankle/physiology , Braces , Movement/physiology , Adult , Humans , United States
8.
Transfus Clin Biol ; 13(1-2): 97-102, 2006.
Article in English | MEDLINE | ID: mdl-16563828

ABSTRACT

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.


Subject(s)
Cation Transport Proteins/physiology , Escherichia coli Proteins/physiology , Quaternary Ammonium Compounds/metabolism , Saccharomyces cerevisiae Proteins/physiology , Ammonia/metabolism , Biological Transport , Blood Proteins/chemistry , Blood Proteins/physiology , Cation Transport Proteins/chemistry , Escherichia coli Proteins/chemistry , Gene Expression Regulation , Humans , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/physiology , Models, Molecular , Nucleotidyltransferases/physiology , PII Nitrogen Regulatory Proteins/physiology , Protein Conformation , Rh-Hr Blood-Group System/chemistry , Rh-Hr Blood-Group System/physiology , Saccharomyces cerevisiae Proteins/chemistry , Signal Transduction , Species Specificity , Structure-Activity Relationship , Substrate Specificity
9.
Biochem Soc Trans ; 33(Pt 1): 170-2, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15667297

ABSTRACT

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.


Subject(s)
Bacteria/metabolism , Bacterial Proteins/metabolism , Cation Transport Proteins/metabolism , Escherichia coli Proteins/metabolism , Nitrogen/metabolism , Operon
10.
Int J Sports Med ; 25(1): 73-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14750017

ABSTRACT

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.


Subject(s)
Contusions/pathology , Muscle, Skeletal/injuries , Muscle, Skeletal/physiology , Ultrasonic Therapy , Animals , Athletic Injuries/rehabilitation , Male , Muscle Fibers, Skeletal/pathology , Proteins/analysis , Rats , Rats, Wistar
11.
Ear Nose Throat J ; 80(8): 536, 539-40, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11523471

ABSTRACT

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.


Subject(s)
Manometry/methods , Nasal Cavity/physiology , Respiration , Acoustics , Humans , Nasal Mucosa/physiology , Otolaryngology/instrumentation , Reproducibility of Results
12.
Arch Phys Med Rehabil ; 82(6): 845-50, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11387593

ABSTRACT

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.


Subject(s)
Body Temperature , Cryotherapy , Muscles/physiology , Skinfold Thickness , Adult , Cryotherapy/methods , Humans , Multivariate Analysis , Regression Analysis , Skin Temperature , Temperature , Time Factors
13.
Microbiol Mol Biol Rev ; 65(1): 80-105, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11238986

ABSTRACT

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.


Subject(s)
Bacteria/genetics , Bacteria/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Nitrogen/metabolism , Signal Transduction , Bacterial Proteins/genetics , Biological Transport , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Cyanobacteria/chemistry , Cyanobacteria/genetics , Cyanobacteria/metabolism , Glutamate-Ammonia Ligase/metabolism , PII Nitrogen Regulatory Proteins , Phosphorylation , Plant Proteins/genetics , Plant Proteins/metabolism , Proteobacteria/chemistry , Proteobacteria/genetics , Proteobacteria/metabolism , Structure-Activity Relationship , Transcription Factors/genetics , Transcription Factors/metabolism
14.
Mol Gen Genet ; 264(5): 555-64, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11212910

ABSTRACT

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.


Subject(s)
Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Down-Regulation , Rhizobium leguminosarum/genetics , Symbiosis , Trans-Activators , Transcription Factors , Amino Acid Sequence , DNA-Binding Proteins/genetics , Gene Expression Regulation, Bacterial , Genes, Regulator , Molecular Sequence Data , Nitrogenase/metabolism , PII Nitrogen Regulatory Proteins , Phenotype , Plasmids/metabolism , Promoter Regions, Genetic , Sequence Homology, Amino Acid , Signal Transduction , Time Factors , beta-Galactosidase/metabolism
15.
Crit Care Med ; 28(9): 3161-5, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11008975

ABSTRACT

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.


Subject(s)
Capillary Permeability/immunology , Esophageal Neoplasms/surgery , Esophagectomy , Gastrectomy , Neutrophils/immunology , Postoperative Complications/immunology , Respiratory Distress Syndrome/immunology , Systemic Inflammatory Response Syndrome/immunology , Aged , Female , Humans , Leukocyte Elastase/blood , Male , Middle Aged , Postoperative Complications/diagnosis , Reference Values , Respiratory Distress Syndrome/diagnosis , Selectins/blood , Systemic Inflammatory Response Syndrome/diagnosis , Thrombomodulin/blood , von Willebrand Factor/metabolism
16.
J Biol Chem ; 275(49): 38452-6, 2000 Dec 08.
Article in English | MEDLINE | ID: mdl-10952972

ABSTRACT

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.


Subject(s)
Bacterial Proteins/metabolism , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Escherichia coli/metabolism , Gene Expression Regulation, Bacterial , Genes, Bacterial , Nitrogen Fixation/genetics , Amino Acid Substitution , Bacterial Proteins/chemistry , Carrier Proteins/genetics , Crystallography, X-Ray/methods , Escherichia coli/genetics , Genotype , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/metabolism , Models, Molecular , Mutagenesis, Site-Directed , Protein Structure, Secondary , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism
17.
Mol Microbiol ; 37(2): 331-44, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10931328

ABSTRACT

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.


Subject(s)
Bacterial Proteins/metabolism , Carrier Proteins/metabolism , Cation Transport Proteins , Escherichia coli Proteins , Escherichia coli/metabolism , Membrane Proteins/metabolism , Alkaline Phosphatase/genetics , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Biological Transport , Blotting, Western , Carrier Proteins/chemistry , Carrier Proteins/genetics , Cell Membrane/physiology , Escherichia coli/chemistry , Evolution, Molecular , Genes, Reporter , Humans , Membrane Proteins/chemistry , Membrane Proteins/genetics , Methylamines/metabolism , Models, Biological , Molecular Sequence Data , Polymerase Chain Reaction , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Homology, Amino Acid , beta-Galactosidase/genetics
18.
Mol Microbiol ; 37(2): 443-52, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10931338

ABSTRACT

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.


Subject(s)
Bacterial Proteins , Gene Expression Regulation, Bacterial , Glutamate-Ammonia Ligase/metabolism , Repressor Proteins/genetics , Rhizobium leguminosarum/genetics , Transcription Factors , Amino Acid Sequence , Base Sequence , Blotting, Northern , DNA-Binding Proteins/metabolism , Genetic Complementation Test , Immunoblotting , Klebsiella pneumoniae/genetics , Molecular Sequence Data , Nucleic Acid Conformation , PII Nitrogen Regulatory Proteins , Promoter Regions, Genetic , Protein Biosynthesis , RNA, Messenger/analysis , Repressor Proteins/metabolism , Rhizobium leguminosarum/metabolism , Trans-Activators/metabolism
19.
Nucleic Acids Res ; 28(13): 2563-70, 2000 07 01.
Article in English | MEDLINE | ID: mdl-10871407

ABSTRACT

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.


Subject(s)
DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/metabolism , Klebsiella pneumoniae/enzymology , Sigma Factor/chemistry , Sigma Factor/metabolism , Amino Acid Sequence , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Bacterial/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , DNA-Directed RNA Polymerases/genetics , Genes, Bacterial/genetics , Genes, Reporter/genetics , Holoenzymes/chemistry , Holoenzymes/genetics , Holoenzymes/metabolism , Klebsiella pneumoniae/genetics , Molecular Sequence Data , Nucleic Acid Conformation , Oxidoreductases/genetics , Promoter Regions, Genetic/genetics , Protein Binding , RNA Polymerase Sigma 54 , Sequence Alignment , Sequence Deletion/genetics , Sigma Factor/genetics , Structure-Activity Relationship , Transcription, Genetic/genetics , Transcriptional Activation/genetics
20.
Intensive Care Med ; 26(2): 202-5, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10784309

ABSTRACT

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.


Subject(s)
Brain Injuries/drug therapy , Brain Injuries/physiopathology , Cerebrovascular Circulation , Intracranial Pressure/drug effects , Norepinephrine/therapeutic use , Vasoconstrictor Agents/therapeutic use , Adolescent , Adult , Analysis of Variance , Blood Flow Velocity/drug effects , Blood Flow Velocity/physiology , Blood Pressure/drug effects , Blood Pressure/physiology , Brain Injuries/metabolism , Female , Glasgow Coma Scale , Humans , Infusions, Intravenous , Intensive Care Units , Intracranial Pressure/physiology , Male , Middle Aged , Norepinephrine/administration & dosage , Oxygen/metabolism , Prospective Studies , Ultrasonography, Doppler, Transcranial , Vasoconstrictor Agents/administration & dosage
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