bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mixed venous oxygen saturation levels do not exclude fluid responsiveness in critically ill septic patients
Authors: Velissaris Dimitrios , Pierrakos Charalampos , Scolletta Sabino , De Backer Daniel , Vincent Jean Louis 
Published: September 2011

Abstract
Introduction
The aim of this study was to determine whether the degree of fluid responsiveness in critically ill septic patients is related to baseline mixed venous oxygen saturation (SvO2) levels. We also sought to define whether fluid responsiveness would be less likely in the presence of a high SvO2 (>70%).

Methods
This observational study was conducted in a 32-bed university hospital medicosurgical ICU. The hemodynamic response to a fluid challenge was evaluated in 65 critically ill patients with severe sepsis. Patients were divided into two groups (responders and nonresponders) according to their cardiac index (CI) response to the challenge (>10% or <10%).

Results
Of the 65 patients, 34 (52%) were fluid responders. Baseline SvO2, CI, heart rate (HR) and mean arterial pressure (MAP) were not statistically different between groups. The responders had lower pulmonary artery occlusion pressure (PAOP) and central venous pressure (CVP) at baseline than the nonresponders. After the fluid challenge, there were no differences between the two groups in MAP, CVP, PAOP or HR. There was no correlation between changes in CI or stroke volume index and baseline SvO2. Receiver operating characteristic analysis showed that SvO2 was not a predictor of fluid responsiveness.

Conclusions
The response of septic patients to a fluid challenge is independent of baseline SvO2. The presence of a high SvO2 does not necessarily exclude the need for further fluid administration.
Transcriptional responses of Burkholderia cenocepacia to polymyxin B in isogenic strains with diverse polymyxin B resistance phenotypes
Authors: Loutet Slade A , Di Lorenzo Flaviana , Clarke Chelsea , Molinaro Antonio , Valvano Miguel A 
Published: September 2011

Abstract

Background

Burkholderia cenocepacia is a Gram-negative opportunistic pathogen displaying high resistance to antimicrobial peptides and polymyxins. We identified mechanisms of resistance by analyzing transcriptional changes to polymyxin B treatment in three isogenic B. cenocepacia strains with diverse polymyxin B resistance phenotypes: the polymyxin B-resistant parental strain K56-2, a polymyxin B-sensitive K56-2 mutant strain with heptoseless lipopolysaccharide (LPS) (RSF34), and a derivative of RSF34 (RSF34 4000B) isolated through multiple rounds of selection in polymyxin B that despite having a heptoseless LPS is highly polymyxin B-resistant.

Results
A heptoseless LPS mutant of B. cenocepacia was passaged through multiple rounds of selection to regain high levels of polymyxin B-resistance. This process resulted in various phenotypic changes in the isolate that could contribute to polymyxin B resistance and are consistent with LPS-independent changes in the outer membrane. The transcriptional response of three B. cenocepacia strains to subinhibitory concentrations of polymyxin B was analyzed using microarray analysis and validated by quantitative Real Time-PCR. There were numerous baseline changes in expression between the three strains in the absence of polymyxin B. In both K56-2 and RSF34, similar transcriptional changes upon treatment with polymyxin B were found and included upregulation of various genes that may be involved in polymyxin B resistance and downregulation of genes required for the synthesis and operation of flagella. This last result was validated phenotypically as both swimming and swarming motility were impaired in the presence of polymyxin B. RSF34 4000B had altered the expression in a larger number of genes upon treatment with polymyxin B than either K56-2 or RSF34, but the relative fold-changes in expression were lower.

Conclusions
It is possible to generate polymyxin B-resistant isolates from polymyxin B-sensitive mutant strains of B. cenocepacia, likely due to the multifactorial nature of polymyxin B resistance of this bacterium. Microarray analysis showed that B. cenocepacia mounts multiple transcriptional responses following exposure to polymyxin B. Polymyxin B-regulated genes identified in this study may be required for polymyxin B resistance, which must be tested experimentally. Exposure to polymyxin B also decreases expression of flagellar genes resulting in reduced swimming and swarming motility.
Experimental annotation of the human pathogen Histoplasma capsulatum transcribed regions using high-resolution tiling arrays
Authors: Voorhies Mark , Foo Catherine K , Sil Anita 
Published: September 2011

Abstract

Background
The fungal pathogen Histoplasma capsulatum is thought to be the most common cause of fungal respiratory infections in immunocompetent humans, yet little is known about its biology. Here we provide the first genome-wide studies to experimentally validate its genome annotation. A functional interrogation of the Histoplasma genome provides critical support for continued investigation into the biology and pathogenesis of H. capsulatum and related fungi.

Results
We employed a three-pronged approach to provide a functional annotation for the H. capsulatum G217B strain. First, we probed high-density tiling arrays with labeled cDNAs from cells grown under diverse conditions. These data defined 6,172 transcriptionally active regions (TARs), providing validation of 6,008 gene predictions. Interestingly, 22% of these predictions showed evidence of anti-sense transcription. Additionally, we detected transcription of 264 novel genes not present in the original gene predictions. To further enrich our analysis, we incorporated expression data from whole-genome oligonucleotide microarrays. These expression data included profiling under growth conditions that were not represented in the tiling experiment, and validated an additional 2,249 gene predictions. Finally, we compared the G217B gene predictions to other available fungal genomes, and observed that an additional 254 gene predictions had an ortholog in a different fungal species, suggesting that they represent genuine coding sequences.

Conclusions
These analyses yielded a high confidence set of validated gene predictions for H. capsulatum. The transcript sets resulting from this study are a valuable resource for further experimental characterization of this ubiquitous fungal pathogen. The data is available for interactive exploration at http://histo.ucsf.edu.
Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation
Authors: Li Ji-Yao , Chai Biaoxin , Zhang Weizhen , Wu Xiaobin , Zhang Chao , Fritze Danielle , Xia Zefeng , Patterson Cam , Mulholland Michael W 
Published: September 2011

Abstract

Background
The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4) is expressed in neuropeptide Y and proopiomelanocortin (POMC) neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s) of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4) is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling.

Results

In situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308.

Conclusions
These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.
Frequency of impulse control behaviours associated with dopaminergic therapy in restless legs syndrome
Authors: Voon Valerie , Schoerling Andrea , Wenzel Sascha , Ekanayake Vindhya , Reiff Julia , Trenkwalder Claudia , Sixel-Döring Friederike 
Published: September 2011

Abstract

Background
Low doses of dopamine agonists (DA) and levodopa are effective in the treatment of restless legs syndrome (RLS). A range of impulse control and compulsive behaviours (ICBs) have been reported following the use of DAs and levodopa in patients with Parkinson's disease. With this study we sought to assess the cross-sectional prevalence of impulse control behaviours (ICBs) in restless legs syndrome (RLS) and to determine factors associated with ICBs in a population cohort in Germany.

Methods
Several questionnaires based on validated and previously used instruments for assessment of ICBs were mailed out to patients being treated for RLS. Final diagnoses of ICBs were based on stringent diagnostic criteria after psychiatric interviews were performed.

Results
10/140 RLS patients of a clinical cohort (7.1%) were finally diagnosed with ICBs, 8 of 10 on dopamine agonist (DA) therapy, 2 of 10 on levodopa. 8 of the 10 affected patients showed more than one type of abnormal behaviour. Among those who responded to the questionnaires 6/140 [4.3%] revealed binge eating, 5/140 [3.6%] compulsive shopping, 3/140 [2.1%] pathological gambling, 3/140 [2.1%] punding, and 2/140 [1.4%] hypersexuality in psychiatric assessments. Among those who did not respond to questionnaires, 32 were randomly selected and interviewed: only 1 patient showed positive criteria of ICBs with compulsive shopping and binge eating. ICBs were associated with higher DA dose (p = 0.001), younger RLS onset (p = 0.04), history of experimental drug use (p = 0.002), female gender (p = 0.04) and a family history of gambling disorders (p = 0.02), which accounted for 52% of the risk variance.

Conclusion
RLS patients treated with dopaminergic agents and dopamine agonists in particular, should be forewarned of potential side effects. A careful history of risk factors should be taken.
Immune reconstitution syndrome presenting as probable AIDS-related lymphoma: a case report
Authors: Mortensen Bo K , Nielsen Susanne D , Christensen Charlotte B , Helweg-Larsen Jannik 
Published: September 2011

Abstract
We report an unusual case of HIV-related immune reconstitution inflammatory syndrome, presenting as suspected AIDS-related lymphoma. Symptoms, initial investigations including fine-needle biopsy and 18F-FDG PET/CT scan were highly compatible with high grade AIDS-related lymphoma, however subsequently IRIS was diagnosed. We discuss pitfalls in the interpretation of diagnostic results in ARL versus IRIS.
Dynorphin is Expressed Primarily by GABAergic Neurons That Contain Galanin in the Rat Dorsal Horn
Authors: Sardella Thomas CP , Polgár Erika , Garzo Francesca , Furuta Takahiro , Kaneko Takeshi , Watanabe Masahiko , Todd Andrew J 
Published: September 2011

Background: The opioid peptide dynorphin is expressed by certain neurons in the superficial dorsal horn of the spinal cord, but little is known about the types of cell that contain dynorphin. In this study, we have used an antibody against the dynorphin precursor preprodynorphin (PPD), to reveal the cell bodies and axons of dynorphin-expressing neurons in the rat spinal cord. The main aims were to estimate the proportion of neurons in each of laminae I-III that express dynorphin and to determine whether they are excitatory or inhibitory neurons. Results: PPD-immunoreactive cells were concentrated in lamina I and the outer part of lamina II (IIo), where they constituted 17% and 8%, respectively, of all neurons. Around half of those in lamina I and 80% of those in lamina II were GABA-immunoreactive. We have previously identified four non-overlapping neurochemical populations of inhibitory interneurons in this region, defined by the presence of neuropeptide Y, galanin, parvalbumin and neuronal nitric oxide synthase. PPD co-localised extensively with galanin in both cell bodies and axons, but rarely or not at all with the other three markers. PPD was present in around 4% of GABAergic boutons (identified by the presence of the vesicular GABA transporter) in laminae I-II. Conclusions: These results show that most dynorphin-expressing cells in the superficial dorsal horn are inhibitory interneurons, and that they largely correspond to the population that is defined by the presence of galanin. We estimate that dynorphin is present in ∼32% of inhibitory interneurons in lamina I and 11% of those in lamina II. Since the proportion of GABAergic boutons that contain PPD in these laminae was considerably lower than this, our findings suggest that these neurons may generate relatively small axonal arborisations.
Minimally invasive presacral approach for revision of an Axial Lumbar Interbody Fusion rod due to fall-related lumbosacral instability: a case report
Authors: Cohen Anders , Miller Larry E. , Block Jon E. 
Published: September 2011

Abstract

Introduction
The purpose of this study was to describe procedural details of a minimally invasive presacral approach for revision of an L5-S1 Axial Lumbar Interbody Fusion rod.

Case presentation
A 70-year-old Caucasian man presented to our facility with marked thoracolumbar scoliosis, osteoarthritic changes characterized by high-grade osteophytes, and significant intervertebral disc collapse and calcification. Our patient required crutches during ambulation and reported intractable axial and radicular pain. Multi-level reconstruction of L1-4 was accomplished with extreme lateral interbody fusion, although focal lumbosacral symptoms persisted due to disc space collapse at L5-S1.
Lumbosacral interbody distraction and stabilization was achieved four weeks later with the Axial Lumbar Interbody Fusion System (TranS1 Inc., Wilmington, NC, USA) and rod implantation via an axial presacral approach.
Despite symptom resolution following this procedure, our patient suffered a fall six weeks postoperatively with direct sacral impaction resulting in symptom recurrence and loss of L5-S1 distraction. Following seven months of unsuccessful conservative care, a revision of the Axial Lumbar Interbody Fusion rod was performed that utilized the same presacral approach and used a larger diameter implant. Minimal adhesions were encountered upon presacral re-entry. A precise operative trajectory to the base of the previously implanted rod was achieved using fluoroscopic guidance. Surgical removal of the implant was successful with minimal bone resection required. A larger diameter Axial Lumbar Interbody Fusion rod was then implanted and joint distraction was re-established. The radicular symptoms resolved following revision surgery and our patient was ambulating without assistance on post-operative day one. No adverse events were reported.

Conclusions
The Axial Lumbar Interbody Fusion distraction rod may be revised and replaced with a larger diameter rod using the same presacral approach.
Bioconversion of paper sludge to biofuel by simultaneous saccharification and fermentation using a cellulase of paper sludge origin and thermotolerant Saccharomyces cerevisiaeTJ14
Authors: Prasetyo Joni , Naruse Kazuya , Kato Tatsuya , Boonchird Chuenchit , Harashima Satoshi , Park Enoch Y 
Published: September 2011

Abstract

Background
Ethanol production from paper sludge (PS) by simultaneous saccharification and fermentation (SSF) is considered to be the most appropriate way to process PS, as it contains negligible lignin. In this study, SSF was conducted using a cellulase produced from PS by the hypercellulase producer, Acremonium cellulolyticus C-1 for PS saccharification, and a thermotolerant ethanol producer Saccharomyces cerevisiae TJ14 for ethanol production. Using cellulase of PS origin minimizes biofuel production costs, because the culture broth containing cellulase can be used directly.

Results
When 50 g PS organic material (PSOM)/l was used in SSF, the ethanol yield based on PSOM was 23% (g ethanol/g PSOM) and was two times higher than that obtained by a separate hydrolysis and fermentation process. Cellulase activity throughout SSF remained at around 60% of the initial activity. When 50 to 150 g PSOM/l was used in SSF, the ethanol yield was 21% to 23% (g ethanol/g PSOM) at the 500 ml Erlenmeyer flask scale. Ethanol production and theoretical ethanol yield based on initial hexose was 40 g/l and 66.3% (g ethanol/g hexose) at 80 h, respectively, when 161 g/l of PSOM, 15 filter paper units (FPU)/g PSOM, and 20% inoculum were used for SSF, which was confirmed in the 2 l scale experiment. This indicates that PS is a good raw material for bioethanol production.

Conclusions
Ethanol concentration increased with increasing PSOM concentration. The ethanol yield was stable at PSOM concentrations of up to 150 g/l, but decreased at concentrations higher than 150 g/l because of mass transfer limitations. Based on a 2 l scale experiment, when 1,000 kg PS was used, 3,182 kFPU cellulase was produced from 134.7 kg PS. Produced cellulase was used for SSF with 865.3 kg PS and ethanol production was estimated to be 51.1 kg. Increasing the yeast inoculum or cellulase concentration did not significantly improve the ethanol yield or concentration.
Reduced clot strength upon admission, evaluated by thrombelastography (TEG), in trauma patients is independently associated with increased 30-day mortality
Authors: Nystrup Kristin B , Windeløv Nis A , Thomsen Annemarie B , Johansson Pär I 
Published: September 2011

Abstract

Introduction
Exsanguination due to uncontrolled bleeding is the leading cause of potentially preventable deaths among trauma patients. About one third of trauma patients present with coagulopathy on admission, which is associated with increased mortality and will aggravate bleeding in a traumatized patient. Thrombelastographic (TEG) clot strength has previously been shown to predict outcome in critically ill patients. The aim of the present study was to investigate this relation in the trauma setting.

Methods
A retrospective study of trauma patients with an injury severity qualifying them for inclusion in the European Trauma Audit and Research Network (TARN) and a TEG analysis performed upon arrival at the trauma centre.

Results
Eighty-nine patients were included. The mean Injury Severity Score (ISS) was 21 with a 30-day mortality of 17%. Patients with a reduced clot strength (maximal amplitude < 50 mm) evaluated by TEG, presented with a higher ISS 27 (95% CI, 20-34) vs. 19 (95% CI, 17-22), p = 0.006 than the rest of the cohort. Clot strength correlated with the amount of packed red blood cells (p = 0.01), fresh frozen plasma (p = 0.04) and platelet concentrates (p = 0.03) transfused during the first 24 hours of admission. Patients with low clot strength demonstrated increased 30-day mortality (47% vs. 10%, p < 0.001). By logistic regression analysis reduced clot strength was an independent predictor of increased mortality after adjusting for age and ISS.

Conclusion
Low clot strength upon admission is independently associated with increased 30-day mortality in trauma patients and it could be speculated that targeted interventions based on the result of the TEG analysis may improve patient outcome. Prospective randomized trials investigating this potential are highly warranted.
Seropositivity is associated with insulin resistance in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register (NOAR): an observational study
Authors: Mirjafari Hoda , Farragher Tracey M , Verstappen Suzanne MM , Yates Allen , Bunn Diane , Marshall Tarnya , Lunt Mark , Symmons Deborah PM , Bruce Ian N 
Published: September 2011

Abstract
Introduction
Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception cohort of patients with early IP.

Methods
Patients with early IP (two or more swollen joints for four or more weeks), aged 18 to 65 years, seen within 24 months of symptom onset were recruited from the Norfolk Arthritis Register (NOAR), a primary-care-based inception cohort. Assessment included joint examination, current and prior therapy and completion of the Health Assessment Questionnaire. Fasting blood was taken for measurement of CVD risk factors, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), C-reactive protein (CRP), and insulin levels. IR was calculated using the homeostatic model assessment (HOMA-IR). We examined factors associated with IR using univariate and multivariable linear regression models.

Results
A total of 196 patients, including 59 (30%) males, were studied with a median (interquartile range, IQR) age and IP symptom duration of 49 (40 to 57) years and 6.7 (4.6 to 10.7) months, respectively. After age and gender adjustment, HOMA-IR was associated with obesity, (β-Coefficient (95% CI); 1.60 (0.96, 2.24)), higher systolic and diastolic blood pressure (0.03 (0.01, 0.05) and 0.04 (0.01, 0.08) respectively), triglycerides (1.06 (0.54, 1.57)), and HDL (-1.38 (-2.17,-0.58)). HOMA-IR was associated with serological status and this association persisted after adjustment for classic CVD risk factors and other IP-related variables (RF β-Coefficient (95% CI); 0.87 (0.20, 1.53) and ACPA β-Coefficient (95% CI); 1.42 (0.70, 2.15)).

Conclusions
Seropositivity for RF or ACPA was associated with IR in this early IP cohort. This association may, in part, explain why seropositive patients have excess CVD mortality.
Short-term effects of combining upright and prone positions in patients with ARDS: a prospective randomized study
Authors: Robak Oliver , Schellongowski Peter , Bojic Andja , Laczika Klaus , Locker Gottfried J , Staudinger Thomas 
Published: September 2011

Abstract
Introduction
Prone position is known to improve oxygenation in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Supine upright (semirecumbent) position also exerts beneficial effects on gas exchange in this group of patients. We evaluated the effect of combining upright and prone position on oxygenation and respiratory mechanics in patients with ALI or ARDS in a prospective randomized cross-over study.

Methods
After turning them prone from a supine position, we randomized the patients to a prone position or combined prone and upright position. After 2 hours, the position was changed to the other one for another 6 hours. The gas exchange and static compliance of the respiratory system, lungs, and chest wall were assessed in the supine position as well as every hour in the prone position.

Results
Twenty patients were enrolled in the study. The PaO2/FiO2 ratio improved significantly from the supine to the prone position and further significantly increased with additional upright position. Fourteen (70%) patients were classified as responders to the prone position, whereas 17 (85%) patients responded to the prone plus upright position compared with the supine position (P = n.s.). No statistically significant changes were found with respect to compliance.

Conclusions
Combining the prone position with the upright position in patients with ALI or ARDS leads to further improvement of oxygenation.

Trial registration
Clinical Trials No. NCT00753129