bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenaline modulates the global transcriptional profile of Salmonella revealing a role in the antimicrobial peptide and oxidative stress resistance responses
Authors: Karavolos MH , Spencer H , Bulmer DM , Thompson A , Winzer K , Williams P , Hinton JCD , Khan CM Anjam 
Published: October 2008

Abstract

Background
The successful interaction of bacterial pathogens with host tissues requires the sensing of specific chemical and physical cues. The human gut contains a huge number of neurons involved in the secretion and sensing of a class of neuroendocrine hormones called catecholamines. Recently, in Escherichia coli O157:H7, the catecholamines adrenaline and noradrenaline were shown to act synergistically with a bacterial quorum sensing molecule, autoinducer 3 (AI-3), to affect bacterial virulence and motility. We wished to investigate the impact of adrenaline on the biology of Salmonella spp.

Results
We have determined the effect of adrenaline on the transcriptome of the gut pathogen Salmonella enterica serovar Typhimurium. Addition of adrenaline led to an induction of key metal transport systems within 30 minutes of treatment. The oxidative stress responses employing manganese internalisation were also elicited. Cells lacking the key oxidative stress regulator OxyR showed reduced survival in the presence of adrenaline and complete restoration of growth upon addition of manganese. A significant reduction in the expression of the pmrHFIJKLM antimicrobial peptide resistance operon reduced the ability of Salmonella to survive polymyxin B following addition of adrenaline. Notably, both phenotypes were reversed by the addition of the β-adrenergic blocker propranolol. Our data suggest that the BasSR two component signal transduction system is the likely adrenaline sensor mediating the antimicrobial peptide response.

Conclusion

Salmonella are able to sense adrenaline and downregulate the antimicrobial peptide resistance pmr locus through the BasSR two component signalling system. Through iron transport, adrenaline may affect the oxidative stress balance of the cell requiring OxyR for normal growth. Both adrenaline effects can be inhibited by the addition of the β-adrenergic blocker propranolol. Adrenaline sensing may provide an environmental cue for the induction of the Salmonella stress response in anticipation of imminent host-derived oxidative stress. However, adrenaline may also serve in favour of the host defences by lowering antimicrobial peptide resistance and hence documenting for the first time such a function for a hormone.
Transglutaminase activity in the hematopoietic tissue of a crustacean, Pacifastacus leniusculus, importance in hemocyte homeostasis
Authors: Lin Xionghui , Söderhäll Kenneth , Söderhäll Irene 
Published: October 2008

Abstract

Background
Transglutaminases (TGases) form a group of enzymes that have many different substrates and among the most well known are fibrin for Factor XIIIa and the clotting protein in crustaceans. We also found that TGase is an abundant protein in the hematopoietic tissue (Hpt) cells of crayfish and hence we have studied the possible function of this enzyme in hematopoiesis.

Results
TGase is one of the most abundant proteins in the Hpt and its mRNA expression as well as enzyme activity is very high in the Hpt cells, lesser in the semi-granular hemocytes and very low in the granular cells. In cultured hematopoietic tissues, high activity was present in cells in the centre of the tissue, whereas cells migrating out of the tissue had very low TGase activity. RNAi experiments using dsRNA for TGase completely knocked down the transcript and as a result the cell morphology was changed and the cells started to spread intensely. If astakine, a cytokine directly involved in hematopoiesis, was added the cells started to spread and adopt a morphology similar to that observed after RNAi of TGase. Astakine had no effect on TGase expression, but after a prolonged incubation for one week with this invertebrate cytokine, TGase activity inside and outside the cells was completely lost. Thus it seems as if astakine addition to the Hpt cells and RNAi of TGase in the cell culture will lead to the same results, i.e. loss of TGase activity in the cells and they start to differentiate and spread.

Conclusion
The results of this study suggest that TGase is important for keeping the Hpt cells in an undifferentiated stage inside the hematopoietic tissue and if expression of TGase mRNA is blocked the cells start to differentiate and spread.
This shows a new function for transglutaminase in preventing hematopoietic stem cells from starting to differentiate and migrate into the hemolymph, whereas their proliferation is unaffected. Astakine is also important for the hematopoiesis, since it induces hemocyte synthesis in the Hpt but now we also show that it in some unknown way participates in the differentiation of the Hpt cells.
Pocket Doppler and vascular laboratory equipment yield comparable results for ankle brachial index measurement
Authors: Nicolaï Saskia PA , Kruidenier Lotte M , Rouwet Ellen V , Wetzels-Gulpers Liliane , Rozeman Constantijn AM , Prins Martin H , Teijink Joep AW 
Published: October 2008

Abstract

Background
The ankle brachial index (ABI) is a well-established tool for screening and diagnosis of peripheral arterial disease (PAD). In this study we assessed the validity of ABI determination using a pocket Doppler device compared with automatic vascular laboratory measurement in patients suspected of PAD.

Methods
Consecutive patients with symptoms of PAD referred for ABI measurement between December 2006 and August 2007 were included. Resting ABI was determined with a pocket Doppler, followed by ABI measurement with automatic vascular laboratory equipment, performed by an experienced vascular technician. The leg with the lowest ABI was used for analysis.

Results
From 99 patients the mean resting ABI was 0.80 measured with the pocket Doppler and 0.85 measured with vascular laboratory equipment. A Bland-Altman plot demonstrated great correspondence between the two methods. The mean difference between the two methods was 0.05 (P < .001). Multivariate linear regression analysis showed no dependency of the difference on either the average measured ABI or affected or unaffected leg.

Conclusion
Since the small, albeit statistically significant, difference between the two methods is not clinically relevant, our study demonstrates that ABI measurements with pocket Doppler and vascular laboratory equipment yield comparable results and can replace each other. Results support the use of the pocket Doppler for screening of PAD, allowing initiation of cardiovascular risk factor management in primary care, provided that the equipment operator is experienced.
Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: A randomised controlled trial in British general practice
Authors: Park Paul , Simmons Rebecca K , Prevost A Toby , Griffin Simon J 
Published: October 2008

Abstract

Background
To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illness perceptions.

Methods
Randomised controlled trial in two general practices in Cambridgeshire. Individuals aged 40–69 without known diabetes were identified as being at high risk of having undiagnosed type 2 diabetes using patient records and a validated risk score (n = 1,280). 355 individuals were randomised in a 2 to 1 ratio into non-invited (n = 238) and invited (n = 116) groups. A stepwise screening programme confirmed the presence or absence of diabetes. Six weeks after the last contact (either test or invitation), a questionnaire was sent to all participants, including non-attenders and those who were not originally invited. Outcome measures included attendance, anxiety (short-form Spielberger State Anxiety Inventory-STAI), self-rated health and diabetes illness perceptions.

Results
95 people (82% of those invited) attended for the initial capillary blood test. Six individuals were diagnosed with diabetes. Invited participants were more anxious than those not invited (37.6 vs. 34.1 STAI, p-value = 0.015), and those diagnosed with diabetes were considerably more anxious than those classified free of diabetes (46.7 vs. 37.0 STAI, p-value = 0.031). Non-attenders had a higher mean treatment control sub-scale (3.87 vs. 3.56, p-value = 0.016) and a lower mean emotional representation sub-scale (1.81 vs. 2.68, p-value = 0.001) than attenders. No differences in the other five illness perception sub-scales or self-rated health were found.

Conclusion
Screening for type 2 diabetes in primary care is feasible but may be associated with higher levels of short-term anxiety among invited compared with non-invited participants.

Trial registration
ISRCTN99175498
The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors
Authors: Rossi Fiorella , Querido Bianca , Nimmagadda Manideepthi , Cocklin Simon , Navas-Martín Sonia , Martín-García Julio 
Published: October 2008

Abstract

Background
HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env) have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen env from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2), we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env.

Results
Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283) has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an env clone from a brain-derived isolate and into a brain tissue-derived env clone, and the T283N change into a spleen-derived env from the same individual; however, we found that their phenotypes were not affected.

Conclusion
We have identified that the V1-V3 region of a brain-derived envelope glycoprotein seems to play a crucial role in determining not only the low CD4 dependence and increased macrophage tropism, but also the augmented fusogenicity and reduced sensitivity to T-1249 and BMS-378806. By contrast, increased sensitivity to HNG-105 mostly correlated with low CD4 dependence and macrophage tropism but was not determined by the presence of the brain's V1-V3 region, confirming that viral determinants of phenotypic changes in brain-derived envelope glycoproteins are likely complex and context-dependent.
The intracellular detection of MIP-1beta enhances the capacity to detect IFN-gamma mediated HIV-1-specific CD8 T-cell responses in a flow cytometric setting providing a sensitive alternative to the ELISPOT
Authors: Kutscher Sarah , Dembek Claudia J , Allgayer Simone , Heltai Silvia , Stadlbauer Birgit , Biswas Priscilla , Nozza Silvia , Tambussi Giuseppe , Bogner Johannes R , Stellbrink Hans J , Goebel Frank D , Lusso Paolo , Tinelli Marco , Poli Guido , Erfle Volker , Pohla Heike , Malnati Mauro , Cosma Antonio 
Published: October 2008

AbstractBackgroundT-cell mediated immunity likely plays an important role in controlling HIV-1 infection and progression to AIDS. Several candidate vaccines against HIV-1 aim at stimulating cellular immune responses, either alone or together with the induction of neutralizing antibodies, and assays able to measure CD8 and CD4 T-cell responses need to be implemented. At present, the IFN-γ-based ELISPOT assay is considered the gold standard and it is broadly preferred as primary assay for detection of antigen-specific T-cell responses in vaccine trials. However, in spite of its high sensitivity, the measurement of the sole IFN-γ production provides limited information on the quality of the immune response. On the other hand, the introduction of polychromatic flow-cytometry-based assays such as the intracellular cytokine staining (ICS) strongly improved the capacity to detect several markers on a single cell level.ResultsThe cumulative analysis of 275 samples from 31 different HIV-1 infected individuals using an ICS staining procedure optimized by our laboratories revealed that, following antigenic stimulation, IFN-γ producing T-cells were also producing MIP-1β whereas T-cells characterized by the sole production of IFN-γ were rare. Since the analysis of the combination of two functions decreases the background and the measurement of the IFN-γ+ MIP-1β+ T-cells was equivalent to the measurement of the total IFN-γ+ T-cells, we adopted the IFN-γ+ MIP-1β+ data analysis system to evaluate IFN-γ-based, antigen-specific T-cell responses. Comparison of our ICS assay with ELISPOT assays performed in two different experienced laboratories demonstrated that the IFN-γ+ MIP-1β+ data analysis system increased the sensitivity of the ICS up to levels comparable to the sensitivity of the ELISPOT assay.ConclusionThe IFN-γ+ MIP-1β+ data evaluation system provides a clear advantage for the detection of low magnitude HIV-1-specific responses. These results are important to guide the choice for suitable highly sensitive immune assays and to build reagent panels able to accurately characterize the phenotype and function of responding T-cells. More importantly, the ICS assay can be used as primary assay to evaluate HIV-1-specific responses without losing sensitivity in comparison to the ELISPOT assay.
Iterative reconstruction of a global metabolic model of Acinetobacter baylyi ADP1 using high-throughput growth phenotype and gene essentiality data
Authors: Durot Maxime , Le Fèvre François , de Berardinis Véronique , Kreimeyer Annett , Vallenet David , Combe Cyril , Smidtas Serge , Salanoubat Marcel , Weissenbach Jean , Schachter Vincent 
Published: October 2008

Abstract

Background
Genome-scale metabolic models are powerful tools to study global properties of metabolic networks. They provide a way to integrate various types of biological information in a single framework, providing a structured representation of available knowledge on the metabolism of the respective species.

Results
We reconstructed a constraint-based metabolic model of Acinetobacter baylyi ADP1, a soil bacterium of interest for environmental and biotechnological applications with large-spectrum biodegradation capabilities. Following initial reconstruction from genome annotation and the literature, we iteratively refined the model by comparing its predictions with the results of large-scale experiments: (1) high-throughput growth phenotypes of the wild-type strain on 190 distinct environments, (2) genome-wide gene essentialities from a knockout mutant library, and (3) large-scale growth phenotypes of all mutant strains on 8 minimal media. Out of 1412 predictions, 1262 were initially consistent with our experimental observations. Inconsistencies were systematically examined, leading in 65 cases to model corrections. The predictions of the final version of the model, which included three rounds of refinements, are consistent with the experimental results for (1) 91% of the wild-type growth phenotypes, (2) 94% of the gene essentiality results, and (3) 94% of the mutant growth phenotypes. To facilitate the exploitation of the metabolic model, we provide a web interface allowing online predictions and visualization of results on metabolic maps.

Conclusion
The iterative reconstruction procedure led to significant model improvements, showing that genome-wide mutant phenotypes on several media can significantly facilitate the transition from genome annotation to a high-quality model.
Evaluation of the safety of high-frequency chest wall oscillation (HFCWO) therapy in blunt thoracic trauma patients
Authors: Anderson Casandra A , Palmer Cassandra A , Ney Arthur L , Becker Brian , Schaffel Steven D , Quickel Robert R 
Published: October 2008

Abstract

Background
Airway clearance is frequently needed by patients suffering from blunt chest wall trauma. High Frequency Chest Wall Oscillation (HFCWO) has been shown to be effective in helping to clear secretions from the lungs of patients with cystic fibrosis, bronchiectasis, asthma, primary ciliary dyskinesia, emphysema, COPD, and many others. Chest wall trauma patients are at increased risk for development of pulmonary complications related to airway clearance. These patients frequently have chest tubes, drains, catheters, etc. which could become dislodged during HFCWO. This prospective observational study was conducted to determine if HFCWO treatment, as provided by The Vest™ Airway Clearance System (Hill-Rom, Saint Paul, MN), was safe and well tolerated by these patients.

Methods
Twenty-five blunt thoracic trauma patients were entered into the study. These patients were consented. Each patient was prescribed 2, 15 minute HFCWO treatments per day using The Vest® Airway Clearance System (Hill-Rom, Inc., St Paul, MN). The Vest® system was set to a frequency of 10–12 Hz and a pressure of 2–3 (arbitrary unit). Physiological parameters were measured before, during, and after treatment. Patients were free to refuse or terminate a treatment early for any reason.

Results
No chest tubes, lines, drains or catheters were dislodged as a result of treatment. One patient with flail chest had a chest tube placed after one treatment due to increasing serous effusion. No treatments were missed and continued without further incident. Post treatment survey showed 76% experienced mild or no pain and more productive cough. Thirty days after discharge there were no deaths or hospital re-admissions.

Conclusion
This study suggests that HFCWO treatment is safe for trauma patients with lung and chest wall injuries. These findings support further work to demonstrate the airway clearance benefits of HFCWO treatment.
Acute renal failure and rhabdomyolysis in a patient with infectious mononucleosis: a case report
Authors: Aloizos Stavros , Gourgiotis Stavros , Oikonomou Konstantinos , Stakia Paraskevi 
Published: October 2008

Abstract
We report a very rare case of acute renal failure and rhabdomyolysis in an Intensive Care treated 20-years-old male with upper airway obstruction due to Epstein-Barr infection.
In our opinion this was a manifestation of the very rare and potentially lethal propofol infusion syndrome and not a direct complication of the underlying infection, although renal biopsy was not performed in our patient.
Burkholderia pseudomallei infection in a patient with diabetes presenting with multiple splenic abscesses and abscess in the foot: a case report
Authors: Dhodapkar Rahul , Sujatha S , Sivasangeetha K , Prasanth G , Parija Subhash Chandra 
Published: October 2008

Abstract

Introduction
Melioidosis or infection with Burkholderia pseudomallei presents with protean manifestations. We present a case of melioidosis in a diabetic patient from India. The case is presented to highlight the importance of early microbiologic diagnosis and subsequent institution of appropriate therapy to achieve a better prognosis

Case presentation
A male bachelor around 50 years of age from India presented with low grade fever, bilateral ankle swelling and hypochondrial pain. On examination patient had diabetes and had multiple abscesses in bilateral ankle, knee and splenic region. Microbiologic diagnosis revealed the etiologic agent to be Burkholderia pseudomallei. Patient was managed with iv ceftazidime and surgical excision.

Conclusion
The case report highlights the importance of early identification of etiologic agent. B. pseudomallei identification requires a great deal of clinical suspicion as well as alertness on the part of the medical microbiologist as these isolates are often reported as Pseudomonas spp. Correct identification of the etiologic agent is essential as B pseudomallei requires prolonged antimicrobial therapy for a better clinical outcome.
Involved-Nodal Radiation Therapy As a Component of Combination Therapy for Limited-Stage Hodgkin's Lymphoma: A Question of Field Size
Authors: Campbell Belinda A. , Voss Nick , Pickles Tom , Morris James , Gascoyne Randy D. , Savage Kerry J. , Connors Joseph M. 
Published: October 2008

Purpose Combined-modality therapy is the standard of care for limited-stage Hodgkin's lymphoma (HL). Radiation therapy has evolved from extended-field radiation therapy (EFRT) to involved-field radiation therapy (IFRT), reducing toxicity while maintaining high cure rates. Recent publications recommend a further reduction to involved-nodal radiation therapy (INRT), however, this has not been clinically validated. Patients and Methods We identified 325 patients with limited-stage HL, diagnosed between May 1, 1989 and April 1, 2005, and treated with chemotherapy and radiation therapy following era-specific guidelines: EFRT until 1996; IFRT from 1996 to 2001; INRT ≤ 5 cm from 2001 to the present. INRT ≤ 5 cm was defined as the prechemotherapy nodal volume with margins ≤ 5 cm to account for physiological movement, set-up variation, and the limitations of conventional simulation and radiation therapy techniques. Exclusion criteria were age younger than 16, fluorine-18 fluorodeoxyglucose positron emission tomography, non–doxorubicin, bleomycin, vinblastine, and dacarbazine-like chemotherapy, and/or more than four chemotherapy cycles. Results At diagnosis, median age was 35 years; 52% male; stage IA 29%; stage IIA 71%. Ninety-five percent of patients received two chemotherapy cycles. The three radiation therapy groups were: EFRT, 39%; IFRT, 30%; and INRT ≤ 5 cm, 31%. Median follow-up of living patients was 80 months. Median time to relapse was 37 months. Twelve relapses occurred: four after EFRT (3%); five after IFRT (5%); and three after INRT ≤ 5 cm (3%; P = .9). No marginal recurrences occurred after INRT ≤ 5 cm. Locoregional relapse (LRR) occurred in five patients: three after EFRT; two with IFRT; and none with INRT ≤ 5 cm. At 5 years, progression-free survival (PFS) was 97%, and overall survival (OS) was 95%. At 10 years, PFS and OS were 95% and 90%, respectively. Conclusion Reduction in field size appears to be safe, without an increased risk of LRR in patients receiving INRT ≤ 5 cm.