bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the antigen encoded by adenoviral vectors to the DEC205 receptor modulates the cellular and humoral immune response
Authors: Tenbusch Matthias , Nchinda Godwin , Storcksdieck genannt Bonsmann Michael , Temchura Vladimir , Überla Klaus 
Published: November 2012

Abstract
Replication-defective adenoviral vectors have emerged as promising vaccine candidates for diseases relying on strong CD8 + T-cell responses for protection. In this study, we modified a non-replicative adenoviral vector to selectively deliver, in situ, an encoded ovalbumin (OVA) model antigen to dendritic cells (DCs). Efficient uptake and presentation of OVA was achieved through fusion of the antigen to a single-chain antibody directed against DEC205, an endocytic receptor expressed on DCs. The immunogenicity of the vaccine was thereby enhanced as demonstrated by elevated antibody levels and increased T-cell responses after low-dose vaccination with 10 7 viral particles compared with a non-targeted control. Nevertheless, after immunization with higher doses of the targeted vaccine, the capacity of vaccine-induced CD8 + T cells to produce the cytokine IL-2 was diminished and the CD8 + T-cell response was dominated by an effector memory phenotype (CD62L – /CD127 + ) in contrast to the effector phenotype (CD62L – /CD127 – ) observed after non-targeted antigen delivery. Interestingly, the protective capacity of the non-targeted vaccine was superior to that of the targeted vaccine in an antigen-specific vaccinia virus infection as well as in a tumor challenge model. In the latter, the low dose of the DC-targeted vaccine also conferred partial protection from tumor growth, demonstrating dose-dependent effects of the DC-targeting on the quality of the vaccine-induced immune response. Significant differences could be observed in regard to the antibody pattern, the functional and phenotypic T-cell repertoire, and to the protective capacity.
Non-thermal emission from pulsar-wind nebulae in starburst galaxies
Authors: Ohm S. , Hinton J. A. 
Published: November 2012

Abstract
The recently detected γ-ray emission from starburst galaxies is most commonly considered to be diffuse emission arising from strong interactions of accelerated cosmic rays. Mannheim, Elsässer & Tibolla, however, have argued that a population of individual pulsar-wind nebulae (PWNe) could be responsible for the detected TeV emission. Here, we show that the starburst environment plays a critical role in the TeV emission from starburst PWN, and perform the first detailed calculations for this scenario. Our approach is based on the measured star formation rates in the starburst nuclei of NGC 253 and M82, assumed pulsar birth periods and a simple model for the injection of non-thermal particles. The two-zone model applied here takes into account the high far-infrared radiation field and different densities and magnetic fields in the PWN and the starburst regions, as well as particle escape. We confirm that PWN can make a significant contribution to the TeV fluxes, provided that the injection spectrum of particles is rather hard and that the average pulsar birth period is rather short (∼35 ms). The PWN contribution should lead to a distinct spectral feature which can be probed by future instruments such as Cherenkov Telescope Array.
Role of the Putative Osmosensor Arabidopsis Histidine Kinase1 in Dehydration Avoidance and Low-Water-Potential Response
Authors: Kumar M. Nagaraj , Jane Wann-Neng , Verslues Paul E. 
Published: November 2012

Abstract
The molecular basis of plant osmosensing remains unknown. Arabidopsis (Arabidopsis thaliana) Histidine Kinase1 (AHK1) can complement the osmosensitivity of yeast (Saccharomyces cerevisiae) osmosensor mutants lacking Synthetic Lethal of N-end rule1 and SH3-containing Osmosensor and has been proposed to act as a plant osmosensor. We found that ahk1 mutants in either the Arabidopsis Nossen-0 or Columbia-0 background had increased stomatal density and stomatal index consistent with greater transpirational water loss. However, the growth of ahk1 mutants was not more sensitive to controlled moderate low water potential (ψw) or to salt stress. Also, ahk1 mutants had increased, rather than reduced, solute accumulation across a range of low ψw severities. ahk1 mutants had reduced low ψw induction of Ɗ1-Pyrroline-5-Carboxylate Synthetase1 (P5CS1) and 9-cis-Epoxycarotenoid Dioxygenase3, which encode rate-limiting enzymes in proline and abscisic acid (ABA) synthesis, respectively. However, neither Pro nor ABA accumulation was reduced in ahk1 mutants at low ψw. P5CS1 protein level was not reduced in ahk1 mutants. This indicated that proline accumulation was regulated in part by posttranscriptional control of P5CS1 that was not affected by AHK1. Expression of AHK1 itself was reduced by low ψw, in contrast to previous reports. These results define a role of AHK1 in controlling stomatal density and the transcription of stress-responsive genes. These phenotypes may be mediated in part by reduced ABA sensitivity. More rapid transpiration and water depletion can also explain the previously reported sensitivity of ahk1 to uncontrolled soil drying. The unimpaired growth, ABA, proline, and solute accumulation of ahk1 mutants at low ψw suggest that AHK1 may not be the main plant osmosensor required for low ψw tolerance.
Metabolic effects of three different inotropic strategies in the newborn piglet myocardium
Authors: COLDING P. D. , KOLSTRUP L. M. , HYLDEBRANDT J. A. , SCHMIDT M. R. , BØTKER H. E. , RAVN H. B. 
Published: November 2012

IntroductionNeonates undergoing congenital heart surgery frequently need post‐operative inotropic support. Knowledge about the effect of inotropes on myocardial metabolism in the newborn heart is limited, and the choice of inotropic therapy is based mainly on evidence from studies in adults. The aim of this study was to compare the effect of three inotropic strategies on the myocardial metabolism in a neonatal pig model.MethodsNewborn piglets were randomised to intravenous infusions with: adrenaline and milrinone; dopamine and milrinone; dobutamine in haemodynamically equivalent doses; or isotonic saline, through 3 h. Microdialysis catheters were inserted in the myocardium of the left and right ventricle, and concentrations of lactate, pyruvate, glycerol, and glucose were measured in the microdialysate. In myocardial biopsies, tissue lactate and intracellular glycogen concentrations were determined, and arterial blood samples were analysed for lactate and glucose.ResultsNo statistically significant differences were observed in haemodynamics between the three interventions. Metabolic variables demonstrated a consistent increase in lactate concentration in blood, myocardial dialysate, and biopsies in milrinone–adrenaline‐treated animals. The lactate concentration remained stable in all other groups in all samples. The myocardial lactate/pyruvate ratio did not increase and was not significantly different between groups.ConclusionMilrinone and adrenaline induced significantly higher lactate levels in neonatal piglets. The increase was not caused by myocardial ischaemia, but rather due to a beta‐stimulation‐induced glycolysis.
Sevoflurane induces short‐term changes in proteins in the cerebral cortices of developing rats
Authors: LI Y. , LIU C. , ZHAO Y. , HU K. , ZHANG J. , ZENG M. , LUO T. , JIANG W. , WANG H. 
Published: November 2012

BackgroundExposure to intravenous or inhaled anesthetic agents has potential deleterious effects on the developing brain. However, the mechanisms are not clear. Herein, we investigated protein expression changes in neonatal rat brains after exposure to sevoflurane, an inhalational anesthetic commonly used for pediatric patients.MethodsSeven‐day‐old rats were treated with 1.8% sevoflurane or 30% oxygen for 4 h. Cerebral cortices were obtained at 3 h and 3 days after sevoflurane exposure for cell apoptosis detection, proteomic analysis and Western blotting.ResultsThere was a significant increase of cleaved caspase 3 at 3 h after sevoflurane exposure. Six proteins had 1.5‐fold or higher changes in expression at 3 h after sevoflurane anesthesia as compared with sham‐treated pups. No proteins had this degree of change at 3 days after sevoflurane anesthesia. Proteins whose expression was downregulated included collapsin response mediator protein‐1 (CRMP‐1), truncated CRMP‐4, beta‐tubulin IIc and neuron‐specific class III beta‐tubulin. These four proteins are important for neuronal migration and differentiation. Adenosine triphosphate synthase beta subunit, a protein associated with energy metabolism, was also downregulated. Guanine nucleotide‐binding protein beta 1, a signaling protein, was upregulated. Sevoflurane also increased phosphorylation of glycogen synthase kinase 3β (GSK‐3β) at 3 h after anesthesia and inhibited the normal increase of GSK‐3β at 72 h after anesthesia.ConclusionThese findings suggest that sevoflurane may cause short‐term neuronal apoptosis and disturbances of neuronal migration, differentiation and energy metabolism in neonatal rat brains, and that these disturbances may contribute to its neurodegenerative effects.
Long‐term effects of a perioperative safety checklist from the viewpoint of personnel
Authors: BÖHMER A. B. , KINDERMANN P. , SCHWANKE U. , BELLENDIR M. , TINSCHMANN T. , SCHMIDT C. , BOUILLON B. , WAPPLER F. , GERBERSHAGEN M. U. 
Published: November 2012

BackgroundWhile positive short‐term effects of the use of safety checklists have previously been reported by personnel, it is unclear to which extent these effects are maintained for a long‐term period. The aim of the present study was to evaluate perioperative safety standards and the quality of interprofessional cooperation from the viewpoint of the involved personnel for up to 2 years following the introduction of a safety checklist.MethodsA survey of 99 co‐workers in the departments of anaesthesiology and traumatology was conducted using a 19‐point questionnaire concerning perioperative safety‐relevant aspects and the quality of interprofessional cooperation before and at 3, 18, and 24 months after the introduction of a safety checklist.ResultsVerification of written consent for surgery (P < 0.01), clear marking of the surgical site (P < 0.01), and time management (P < 0.05) were rated more positively over time by the anaesthesiologists and nurses. Items involving communication were rated less positively after 18 and 24 months than at 3 months. Orthopaedic surgeons rated being better informed about the patients (P < 0.05), the planned operation (P < 0.01), and the assignment of tasks during surgery (P < 0.01) progressively more positively over the time.ConclusionsSome positive effects concerning the perioperative organisation and management were rated more positively even 2 years after checklist implementation. However, interprofessional communication and cooperation did not show long‐term improvement from staff members' point of view. Probably longer lasting effects for the latter aspects could be achieved by repeated instruction and communication training.
CNAP® does not reliably detect minimal or maximal arterial blood pressures during induction of anaesthesia and tracheal intubation
Authors: GAYAT E. , MONGARDON N. , TUIL O. , SIEVERT K. , CHAZOT T. , LIU N. , FISCHLER M. 
Published: November 2012

BackgroundCNAP® provides continuous non‐invasive arterial pressure (AP) monitoring. We assessed its ability to detect minimal and maximal APs during induction of general anaesthesia and tracheal intubation.MethodsFifty‐two patients undergoing surgery under general anaesthesia were enrolled. Invasive pressure monitoring was established at the radial artery, and CNAP monitoring using a finger sensor recording was begun before induction. Statistical analysis was conducted with the Bland–Altman method for comparison of repeated measures and intraclass correlation coefficient (ICC).ResultsPatients’ median age was 67 years [interquartile range (59–76)], median American Society of Anesthesiologists score was 3 [interquartile range (2–3)]. Bias was 5 and −7 mmHg for peak and nadir systolic AP (SAP), with upper and lower limits of agreement of (42:−32) and (27;−42), respectively. The corresponding ICC values were 0.74 [95% confidence interval (CI) = 0.57–0.84] and 0.60 (95% CI = 0.44–0.73). Time lags to reach these values were 7.5 s (95% CI = −10.0 to 60.0) for the highest SAP and 10 s (95% CI = −12.5 to 72.5) for the lowest SAP. Bias, lower and upper limits of agreement for diastolic, and mean AP were −14 (−36 to 9) and −12 (−37 to 13) for the nadir value and −7 (−29 to 15) and −2 (−28 to 25) for the peak value.ConclusionsThe CNAP monitor could detect acute change in AP within a reasonable time lag. Precision of its measurements is not satisfactory, and therefore, it could only serve as a clue to the occurrence of changes in AP.
Is there any correlation between HLA‐DR expression in laryngeal mucosa and interleukin gene variation in sudden infant death syndrome?
Authors: Ferrante Linda , Opdal Siri H , Vege Åshild , Rognum Torleiv O 
Published: November 2012

AbstractAimThe mucosal immune system and cytokines are activated in a large proportion of cases of sudden infant death syndrome (SIDS). Our aim was to search for a possible association between cytokine polymorphisms and immune stimulation of the laryngeal mucosal in SIDS.MethodsHLA‐DR expression in laryngeal mucosal glands and surface epithelium in 97 SIDS victims was evaluated applying a semi‐quantitative scoring system. The findings were related to cytokine gene polymorphisms as well as to the level of various cytokines in the cerebrospinal fluid (CSF). A risk score was established: a score of 0 prepresenting negative HLA‐DR, supine position and no fever prior to death.ResultsThe IL‐6 ‐176CG/CC genotype was found in 92.3% of the SIDS cases with positive score for all risk factors (p = 0.01). Infants with high HLA‐DR score had high levels of IL‐6 in the cerebrospinal fluid (>30 μg/L) (p = 0.005). Furthermore, the IL‐8 SNPs ‐781 CT/TT genotypes and −251 AA/AT genotypes were observed in 93% of the SIDS cases with one or more of the risk factors present compared with SIDS cases no risk factors reported (p = 0.003 and p = 0.016, respectively).ConclusionThis study adds further evidence to the hypothesis that there are genetically associated disturbances of immunological homoeostasis in SIDS.
Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy
Authors: Molnár T. , Lakatos P. L. , Farkas K. , Nagy F. , Szepes Z. , Miheller P. , Horváth G. , Papp M. , Palatka K. , Nyári T. , Bálint A. , Lőrinczy K. , Wittmann T. 
Published: November 2012

SummaryBackgroundSome of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy.AimTo assess the disease course and frequency of relapse of Crohn's disease (CD) following discontinuation of biological therapy, and to determine predictive factors for relapse.MethodsOne hundred twenty‐one CD patients who had achieved clinical remission following 1 year of biological therapy and for whom biological therapy was then discontinued participated in this prospective observational study. Eighty‐seven CD patients had received infliximab and 34 adalimumab. The definition of relapse was an increase of >100 points in CDAI to at least a CDAI of 150 points.ResultsBiological therapy was restarted within 1 year of treatment cessation in 45% of patients. Logistic regression analysis revealed that previous biological therapy (P = 0.011) and dose intensification during the 1‐year course of biological therapy (P = 0.024) were associated with the need for and the time to the restarting of biological therapy. Smoking was observed to have an effect that was not statistically significant (P = 0.053).ConclusionsBiological therapy was restarted a median of 6 months after discontinuation in almost half of Crohn's disease patients in who had been in clinical remission following 1 year of biological therapy. These results suggest that, in the event of the presence of certain predictive factors, biological therapy should probably be continued for more than 1 year by most patients.
Enhanced anti‐tumour effects of Vinca alkaloids given separately from cytostatic therapies
Authors: Ehrhardt H , Pannert L , Pfeiffer S , Wachter F , Amtmann E , Jeremias I 
Published: November 2012

Background and PurposeIn polychemotherapy protocols, that is for treatment of neuroblastoma and Ewing sarcoma, Vinca alkaloids and cell cycle‐arresting drugs are usually administered on the same day. Here we studied whether this combination enables the optimal antitumour effects of Vinca alkaloids to be manifested.Experimental ApproachVinca alkaloids were tested in a preclinical mouse model in vivo and in vitro in combination with cell cycle‐arresting drugs. Signalling pathways were characterized using RNA interference.Key ResultsIn vitro, knockdown of cyclins significantly inhibited vincristine‐induced cell death indicating, in accordance with previous findings, Vinca alkaloids require active cell cycling and M‐phase transition for induction of cell death. In contrast, anthracyclines, irradiation and dexamethasone arrested the cell cycle and acted like cytostatic drugs. The combination of Vinca alkaloids with cytostatic therapeutics resulted in diminished cell death in 31 of 36 (86%) tumour cell lines. In a preclinical tumour model, anthracyclines significantly inhibited the antitumour effect of Vinca alkaloids in vivo. Antitumour effects of Vinca alkaloids in the presence of cytostatic drugs were restored by caffeine, which maintained active cell cycling, or by knockdown of p53, which prevented drug‐induced cell cycle arrest. Therapeutically most important, optimal antitumour effects were obtained in vivo upon separating the application of Vinca alkaloids from cytostatic therapeutics.Conclusion and ImplicationsClinical trials are required to prove whether Vinca alkaloids act more efficiently in cancer patients if they are applied uncoupled from cytostatic therapies. On a conceptual level, our data suggest the implementation of polychemotherapy protocols based on molecular mechanisms of drug–drug interactions.Linked ArticleThis article is commented on by Solary, pp 1555–1557 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12101
Sphingosine and the transient receptor potential channel kinase(s)
Authors: Rohacs Tibor 
Published: November 2012

Transient receptor potential melastatin 7 (TRPM7) is a multifunctional ion channel playing crucial roles during development. TRPM7 is a member of the highly diverse TRP ion channel family. Most TRP channels are regulated by membrane phospholipids, especially phosphoinositides. In this issue of the British Journal of Pharmacology, Qin et al. describes the regulation of TRPM7 and its close homologue TRPM6 by a different kind of membrane lipid: sphingosine. The study finds that sphingosine is a potent and specific inhibitor of TRPM7 and TRPM6 channels. This commentary briefly summarizes the findings of the study, their potential significance and discusses open question and future directions.Linked ArticleThis article is a commentary on Xin Qin et al., pp. 1294–1312 of this issue. To view this paper visit http://dx.doi.org/10.1111/bph.12012
The effect of load on heat production, thermal effects and expenditure of time during implant site preparation – an experimental ex vivo comparison between piezosurgery and conventional drilling
Authors: Stelzle Florian , Frenkel Carsten , Riemann Max , Knipfer Christian , Stockmann Philipp , Nkenke Emeka 
Published: November 2012

AbstractObjectivesPiezoelectric surgery (PS) is meant to be a gentle osteotomy method. The aim of this study was to compare piezosurgical vs. conventional drilling methods for implant site preparation (ISP) – focusing on load‐dependent thermal effect on hard tissue and the expenditure of ISP time.Materials and methodsThree hundred and sixty ISP were performed on ex vivo pig heads using piezosurgery, spiral burs (SB) and trephine burs (TB). The load applied was increased from 0 to 1000 g in 100‐g intervals. Temperature within the bone was measured with a thermocouple, and duration was recorded with a stop watch. Thermal effects were histomorphometrically analysed. Twelve ISPs per technique were performed at the lateral wall of the maxillary sinus.ResultsPS yields the highest mean temperatures (48.6 ± 3.4°C) and thermal effects (200.7 ± 44.4 μm), both at 900–1000 g. Duration is reduced with a plus of load and significantly longer in either case for PS (P < 0.05). There is a correlation of the applied load with all other examined factors for PS and TB. Temperature and histological effects decrease for SB beyond 500 g.ConclusionsPS yields significantly higher temperatures and thermal tissue alterations on load levels higher than 500 g and is significantly slower for ISP compared to SB and TB. For ISP with PS, a maximum load of 400 g should be maintained.
Time Course of Right Ventricular Remodeling after Percutaneous Atrial Septal Defect Closure: Assessment of Regional Deformation Properties with Two‐Dimensional Strain and Strain Rate Imaging
Authors: Eroglu Elif , Cakal Sinem Deniz , Cakal Beytullah , Dundar Cihan , Alici Gokhan , Ozkan Birol , Yazicioglu Mehmet Vefik , Tigen Kursat , Esen Ali Metin 
Published: November 2012

Background: Quantitative assessment of the right ventricular (RV) function in atrial septal defect (ASD) patients before and after closure remains difficult. The aim of this study was to assess the regional RV function in ASD patients, to evaluate the extent and time course of RV remodeling following ASD closure, and to investigate whether any regional difference exists in RV remodeling. Methods: Twenty patients with ASD and 20 age‐matched controls were included. All underwent standard echocardiography and two‐dimensional strain (S) and strain rate (SR) imaging by speckle tracking before, and 24 hours and 1 month after the defect closure. Results: Right ventricular S was higher in ASD patients except apical lateral segment S, which was lower when compared with controls. There was no difference in RV SR between ASD patients and controls. RV septal S and SR, and lateral SR decreased in 24 hours after the procedure and remained the same at 1 month. RV lateral basal and mid S decreased and apical S increased in 24 hours after the closure. All 3 segments showed some more increase at 1 month. RV apical S showed strong correlations with systolic pulmonary artery pressure and global RV systolic function indices. Conclusions: Chronic volume overload in ASD patients causes alterations in RV deformation. Percutaneous closure results in rapid remodeling and normalization of RV deformation. The major geometrical and deformational changes are completed in 24 hours. Lateral wall S seems to reflect the RV deformational changes due to volume loading and unloading better than SR in ASD patients.
A current approach to superficial vein thrombosis
Authors: Ellis Martin H. , Fajer Simone 
Published: November 2012

AbstractSuperficial vein thrombosis (SVT) is an entity commonly encountered in practice. While the clinical diagnosis is reasonably straightforward, care must be taken to exclude concurrent thrombosis of the deep veins, and the possibility of the presence of occult systemic illness such as malignancy should be considered. Recent studies of the epidemiology of SVT demonstrate a high incidence of concurrent deep vein thrombosis emphasizing the need for surveying the deep veins using compression ultrasonography.Treatment decisions are may now be based upon the results of randomized clinical trials and should include a period of anticoagulation using fondaparinux or a low molecular weight heparin. The appropriate doses and duration of therapy are not fully established, and the cost‐effectiveness of these drugs for the treatment of SVT needs further evaluation.