bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardizing the intensity of upper limb treatment in rehabilitation medicine
Authors: Wallace AC , Talelli P. , Dileone M. , Oliver R. , Ward N. , Cloud G. , Greenwood R. , Di Lazzaro V. , Rothwell JC , Marsden JF
Published: March 2010

Objective: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation.

Design: The protocol is described (Part 1) and feasibility and effect explored (Part 2).

Subjects: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp.

Interventions: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months.

Outcome measures: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale.

Results: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13—15)). The mean ARAT score significantly increased by 6.8 points (χ2(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved.

Conclusions: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person’s residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.
The Relationship Between Seclusion and Restraint Use and Childhood Abuse Among Psychiatric Inpatients
Authors: Hammer Joseph H. , Springer Justin , Beck Niels C. , Menditto Anthony , Coleman James
Published: March 2010

Seclusion and restraint (S/R) is a controversial topic in the field of psychiatry, due in part to the high rates of childhood physical and sexual abuse found among psychiatric inpatients. The trauma-informed care perspective suggests that the use of S/R with previously abused inpatients may result in retraumatization due to mental associations between childhood trauma and the experience during S/R. Thus, though one would expect to see efforts on the part of inpatient psychiatric facilities to limit S/R of previously abused inpatients, research suggests that trauma victims may be more likely to experience S/R. The current study sought to clarify this possibility by examining whether presence or absence and chronicity of childhood sexual and physical abuse differed among three groups of adult inpatients ( N = 622) residing at a mid-Western state psychiatric hospital. These groups are empirically derived on the basis of dramatic differences in the patterning of their exposure to S/R over the course of hospitalization. Results of Chi-square and Kruskal—Wallis tests suggest that the classes did not significantly differ in presence or absence and chronicity of childhood sexual or physical abuse when male and female inpatients were analyzed separately. However, among the class of inpatients who experienced the most instances of S/R, 70% of the members have histories of childhood abuse. Implications for inpatients, clinicians, and policy makers are discussed.
Cardiovascular Health and Education as Sources of Individual Variability in Cognitive Aging Among African Americans
Authors: Aiken Morgan Adrienne T. , Sims Regina C. , Whitfield Keith E.
Published: March 2010

Objective: To examine the interrelated effects of cardiovascular health, education, and cognitive functioning in African Americans. Method: The present study utilized data from the Baltimore Study of Black Aging to examine whether (a) cardiovascular health and educational attainment predicted cognitive functioning, after controlling for age, and (b) there was an interaction between cardiovascular health and education in predicting cognitive functioning. Results: Using hierarchical regression analyses, results showed education was significant for all cognitive measures; however, cardiovascular health was significant for only three. Discussion: These findings suggest that although self-reported cardiovascular health contributes to variability in late life cognition in African Americans, education is a more universal predictor that should be further examined.
Cross-Cultural Comparison of the Perceptions and Experiences of Dementia Care Mapping “Mappers” in the United States and the United Kingdom
Authors: Douglass Carolinda , Keddie Arlene , Brooker Dawn , Surr Claire
Published: March 2010

Objectives: Survey results from 161 respondents trained in dementia care mapping (DCM) in the United States and United Kingdom (82 and 79 respondents, respectively) addressed the following: (a) To what extent are mappers using DCM? (b) How satisfied are mappers with DCM? (c) What affect does DCM have on mappers’ attitudes toward their dementia practice? and (d) What challenges are encountered by mappers in the use of DCM? Method: Analyses using odds ratios were used to make international and training-level (basic vs. advanced) comparisons. Results: Differences across countries were found in use of DCM and lack of satisfaction using DCM codes. Similarities were found with positive affects of DCM on attitudes and lack of time for DCM. Discussion: Differences in mappers’ experiences and perceptions exist across the two countries, warranting increased attention to the cultural contexts within which mappers are situated and how these affect the implementation of DCM within a country.
Peer talk as a ‘double opportunity space’: The case of argumentative discourse
Authors: Zadunaisky Ehrlich Sara , Blum-Kulka Shoshana
Published: March 2010

We propose a theoretical view of peer talk as a ‘double opportunity space’, functioning concurrently on the plane of meaning making within childhood culture, as a locus for the co-construction of children’s social world and peer culture, while at the same time affording opportunities for the development of discursive learning (Blum-Kulka, 2005; Blum-Kulka et al., 2004: 308). In the present article, we provide further evidence for this twofold concept by analyzing peer talk in preschoolers’ genre of argumentation in natural interactions. We show that argumentative events, identified in peer talk, indeed display affordances on both planes. On the plane of childhood culture, we pinpoint the ways argumentative events maintain and/or transform the social order and display features of children’s culture. On the developmental plane, we show how children’s argumentative moves and discursive strategies incorporate innovative child-unique strategies, as well as strategies which echo discursive conventions from the adult culture, allowing for the refinement of both types of strategies through interactional display. These findings illustrate the integration of a cultural and a developmental approach within one model of peer talk discursive events.
Public Support for the “Regional Perspective”: A Consideration of Religion
Authors: Owens Michael Leo
Published: March 2010

Factors beside material self-interest may explain public attitudes toward cross-community sharing of resources in metropolitan areas. This article considers whether religion is a factor that influences public support for this regional perspective. Employing original survey data from metropolitan areas in Georgia, it examines the effects of religious tradition and religious salience on the breadth and strength of public support for the regional perspective, holding other factors constant (e.g., suburban residence and homeownership). The findings provide evidence that the choices people may make in metropolitan areas regarding whether to commune with others are open to multiple sources of influence, inclusive of religion.
Benign multiple sclerosis in Crete
Authors: Mastorodemos V. , Nikolakaki H. , Tzagournissakis M. , Kotzamani D. , Panou T. , Spanaki C. , Klados G. , Maris T. , Kontolaimaki E. , Psaroudaki K. , Chlouverakis G. , Georgakakis G. , Plaitakis A.
Published: March 2010

Our objective was to study multiple sclerosis on Crete, an island of 0.6 million inhabitants sharing a similar genetic background and the same environment. Case ascertainment was achieved using the MS Epidemiology Program Project of Crete. The diagnosis and classification of multiple sclerosis were made by established clinical and magnetic resonance imaging criteria, and disease evolution was assessed by periodic evaluations. Thorough clinical and laboratory evaluations were conducted; a detailed history, including a questionnaire of 36 items, was taken. Data obtained were analysed for possible interaction with disease prognosis. We identified 587 cases of multiple sclerosis (F:M = 1.6), >90% of which were of Cretan origin from both parental lines. Age at onset was 31.5 ± 10.3 years (mean ± SD) and disease duration 12.7 ± 9.1 years. About 84.6% had relapsing remitting multiple sclerosis, 9.4% primary progressive multiple sclerosis and 6% clinically isolated syndrome. Nearly 40% of our multiple sclerosis patients with disease duration >10 years (mean = 16.2 ± 5.3 years) remained with no or mild disability (Expanded Disability Status Scale [EDSS] ≤3). Also, about 30% of patients with relapsing remitting multiple sclerosis showed benign disease evolution (EDSS ≤3) more than 20 years (mean = 24.0 ± 3.3) after onset. Factors predisposing to benign multiple sclerosis included younger age at onset, shorter disease duration and a lower number of relapses. We conclude that a substantial proportion of patients with multiple sclerosis from Crete follow a rather benign disease course, and this may relate to the genetic background of the population and/or to environmental factors.
Endothelium-dependent vasodilation is associated with exercise capacity in smokers and non-smokers
Authors: Heffernan Kevin S , Karas Richard H , Patvardhan Eshan A , Kuvin Jeffrey T
Published: March 2010

Smoking is an established cardiovascular risk factor that impairs endothelial function and reduces exercise capacity. Peripheral vascular endothelial function correlates with exercise capacity, but whether this association prevails in smokers is unknown. The purpose of this investigation was to examine the association between endothelial function and exercise capacity in chronic smokers and non-smoking controls. Brachial artery flow-mediated dilation (FMD, endothelium-dependent) following 5 minutes of upper arm occlusion was compared in 26 smokers (age 58 ± 2 years; 15 female; BMI (body mass index) = 28 ± 1) and 39 non-smokers (age 58 ± 2 years; 24 female; BMI = 28 ± 1) using ultrasound. Exercise treadmill time (ETT) was recorded from a standard Bruce protocol during symptom limited stress testing. There was found to be a significant positive association between FMD and ETT in smokers ( r = 0.60, p < 0.05) and non-smokers ( r = 0.28, p < 0.05). FMD was significantly lower in smokers versus non-smokers (8.9 ± 0.9 vs 12.6 ± 0.7%, p < 0.05). ETT was significantly lower in smokers (425 ± 35 seconds) versus non-smokers (522 ± 25 seconds, p < 0.05). After adjusting for FMD, there were no longer group differences in ETT. When patients were matched according to FMD, there were no differences in ETT between smokers and non-smokers. In conclusion, peripheral endothelial dysfunction is a correlate of low exercise capacity in smokers and non-smokers alike. Future research is needed to examine if improving endothelial function will lead to concomitant increases in exercise capacity in chronic smokers.
An isometric hand tester: quantifying motor function in the hand
Authors: Raschner C. , Platzer H.-P. , Patterson C. , Zeppetzauer M. , Frari B. Del , Estermann D. , Piza-Katzer H.
Published: March 2010

The aim of this study was to develop and assess an isometric hand tester to measure multiple strength parameters of the muscles of the hand. Nineteen men and 22 women took part in a first study and 17 men were tested in a second one. Five different tests were developed: wrist flexion, wrist extension, metacarpophalangeal joint flexion, thumb adduction and proximal and distal interphalangeal joint flexion. Reliability was tested with an intraclass correlation coefficient for single measures. When the results from men and women were analysed separately, all tests except metacarpophalangeal joint flexion and thumb adduction produced intraclass correlation coefficients greater than 0.7. Combining the genders gave intraclass correlation coefficients greater than 0.9 except for metacarpophalangeal joint flexion and thumb adduction. After adjustments, intraclass correlation coefficients for metacarpophalangeal joint flexion and thumb adduction were between 0.70 and 0.83 in the second study. The new isometric hand tests improve the measurement of intrinsic and extrinsic hand muscle strength.
Integrin and CD3/TCR activation are regulated by the scaffold protein AKAP450
Authors: Robles-Valero Javier , Martín-Cófreces Noa B. , Lamana Amalia , Macdonald Stephen , Volkov Yuri , Sánchez-Madrid Francisco
Published: March 2010

During antigen recognition by T cells, membrane receptors and cytoskeletal molecules form a specialized structure at the T cell–antigen-presenting cell junction called the immune synapse (IS). We report a role for the scaffolding protein A-kinase anchoring protein-450 (AKAP450), a member of the A-kinase anchoring protein family, in IS formation and T-cell signaling in antigen- and superantigen-dependent T-cell activation. Suppression of AKAP450 by overexpression of a dominant-negative form or siRNA knockdown disrupted the positioning and conformational activation of lymphocyte function-associated antigen 1 at the IS and impaired associated signaling events, including phosphorylation of phospholipase C-γ1 and protein kinase C-θ. AKAP450 was also required for correct activation and phosphorylation of CD3, LAT, and Vav1, key T-cell receptor-activated intracellular signaling molecules. Consistently, antigen-triggered reorientation of the microtubule-organizing center at the IS and interleukin-2 secretion were diminished in AKAP450-disrupted T cells. These results indicate key roles for AKAP450 in the organization and activation of receptor molecules at the IS during T-cell signaling events.
A new protein binding pocket similarity measure based on comparison of clouds of atoms in 3D: application to ligand prediction
Authors: Hoffmann Brice , Zaslavskiy Mikhail , Vert Jean-Philippe , Stoven Véronique
Published: March 2010

Background

Predicting which molecules can bind to a given binding site of a protein with known 3D structure is important to decipher the protein function, and useful in drug design. A classical assumption in structural biology is that proteins with similar 3D structures have related molecular functions, and therefore may bind similar ligands. However, proteins that do not display any overall sequence or structure similarity may also bind similar ligands if they contain similar binding sites. Quantitatively assessing the similarity between binding sites may therefore be useful to propose new ligands for a given pocket, based on those known for similar pockets.

Results

We propose a new method to quantify the similarity between binding pockets, and explore its relevance for ligand prediction. We represent each pocket by a cloud of atoms, and assess the similarity between two pockets by aligning their atoms in the 3D space and comparing the resulting configurations with a convolution kernel. Pocket alignment and comparison is possible even when the corresponding proteins share no sequence or overall structure similarities. In order to predict ligands for a given target pocket, we compare it to an ensemble of pockets with known ligands to identify the most similar pockets. We discuss two criteria to evaluate the performance of a binding pocket similarity measure in the context of ligand prediction, namely, area under ROC curve (AUC scores) and classification based scores. We show that the latter is better suited to evaluate the methods with respect to ligand prediction, and demonstrate the relevance of our new binding site similarity compared to existing similarity measures.

Conclusions

This study demonstrates the relevance of the proposed method to identify ligands binding to known binding pockets. We also provide a new benchmark for future work in this field. The new method and the benchmark are available at http://cbio.ensmp.fr/paris/.
High-throughput and single-cell imaging of NF-κB oscillations using monoclonal cell lines
Authors: Bartfeld Sina , Hess Simone , Bauer Bianca , Machuy Nikolaus , Ogilvie Lesley A , Schuchhardt Johannes , Meyer Thomas F
Published: March 2010

Background

The nuclear factor-κB (NF-κB) family of transcription factors plays a role in a wide range of cellular processes including the immune response and cellular growth. In addition, deregulation of the NF-κB system has been associated with a number of disease states, including cancer. Therefore, insight into the regulation of NF-κB activation has crucial medical relevance, holding promise for novel drug target discovery. Transcription of NF-κB-induced genes is regulated by differential dynamics of single NF-κB subunits, but only a few methods are currently being applied to study dynamics. In particular, while oscillations of NF-κB activation have been observed in response to the cytokine tumor necrosis factor α (TNFα), little is known about the occurrence of oscillations in response to bacterial infections.

Results

To quantitatively assess NF-κB dynamics we generated human and murine monoclonal cell lines that stably express the NF-κB subunit p65 fused to GFP. Furthermore, a high-throughput assay based on automated microscopy coupled to image analysis to quantify p65-nuclear translocation was established. Using this assay, we demonstrate a stimulus- and cell line-specific temporal control of p65 translocation, revealing, for the first time, oscillations of p65 translocation in response to bacterial infection. Oscillations were detected at the single-cell level using real-time microscopy as well as at the population level using high-throughput image analysis. In addition, mathematical modeling of NF-κB dynamics during bacterial infections predicted masking of oscillations on the population level in asynchronous activations, which was experimentally confirmed.

Conclusions

Taken together, this simple and cost effective assay constitutes an integrated approach to infer the dynamics of NF-κB kinetics in single cells and cell populations. Using a single system, novel factors modulating NF-κB can be identified and analyzed, providing new possibilities for a wide range of applications from therapeutic discovery and understanding of disease to host-pathogen interactions.
Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2+P253R mice
Authors: Wang Yingli , Sun Miao , Uhlhorn Victoria L , Zhou Xueyan , Peter Inga , Martinez-Abadias Neus , Hill Cheryl A , Percival Christopher J , Richtsmeier Joan T , Huso David L , Jabs Ethylin Wang
Published: March 2010

Background

Apert syndrome is characterized by craniosynostosis and limb abnormalities and is primarily caused by FGFR2 +/P253R and +/S252W mutations. The former mutation is present in approximately one third whereas the latter mutation is present in two-thirds of the patients with this condition. We previously reported an inbred transgenic mouse model with the Fgfr2 +/S252W mutation on the C57BL/6J background for Apert syndrome. Here we present a mouse model for the Fgfr2+/P253R mutation.

Results

We generated inbred Fgfr2+/P253Rmice on the same C56BL/6J genetic background and analyzed their skeletal abnormalities. 3D micro-CT scans of the skulls of the Fgfr2+/P253Rmice revealed that the skull length was shortened with the length of the anterior cranial base significantly shorter than that of the Fgfr2+/S252Wmice at P0. The Fgfr2+/P253Rmice presented with synostosis of the coronal suture and proximate fronts with disorganized cellularity in sagittal and lambdoid sutures. Abnormal osteogenesis and proliferation were observed at the developing coronal suture and long bones of the Fgfr2+/P253Rmice as in the Fgfr2+/S252Wmice. Activation of mitogen-activated protein kinases (MAPK) was observed in the Fgfr2+/P253Rneurocranium with an increase in phosphorylated p38 as well as ERK1/2, whereas phosphorylated AKT and PKCα were not obviously changed as compared to those of wild-type controls. There were localized phenotypic and molecular variations among individual embryos with different mutations and among those with the same mutation.

Conclusions

Our in vivo studies demonstrated that the Fgfr2 +/P253R mutation resulted in mice with cranial features that resemble those of the Fgfr2+/S252Wmice and human Apert syndrome. Activated p38 in addition to the ERK1/2 signaling pathways may mediate the mutant neurocranial phenotype. Though Apert syndrome is traditionally thought to be a consistent phenotype, our results suggest localized and regional variations in the phenotypes that characterize Apert syndrome.
Characterization of the ovine ribosomal protein SA gene and its pseudogenes
Authors: Van den Broeke Alice , Van Poucke Mario , Marcos-Carcavilla Ane , Hugot Karine , Hayes Hélène , Bertaud Maud , Van Zeveren Alex , Peelman Luc J
Published: March 2010

Background

The ribosomal protein SA (RPSA), previously named 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR) is a multifunctional protein that plays a role in a number of pathological processes, such as cancer and prion diseases. In all investigated species, RPSA is a member of a multicopy gene family consisting of one full length functional gene and several pseudogenes. Therefore, for studies on RPSA related pathways/pathologies, it is important to characterize the whole family and to address the possible function of the other RPSA family members. The present work aims at deciphering the RPSA family in sheep.

Results

In addition to the full length functional ovine RPSA gene, 11 other members of this multicopy gene family, all processed pseudogenes, were identified. Comparison between the RPSA transcript and these pseudogenes shows a large variety in sequence identities ranging from 99% to 74%. Only one of the 11 pseudogenes, i.e. RPSAP7, shares the same open reading frame (ORF) of 295 amino acids with the RPSA gene, differing in only one amino acid. All members of the RPSA family were annotated by comparative mapping and fluorescence in situ hybridization (FISH) localization. Transcription was investigated in the cerebrum, cerebellum, spleen, muscle, lymph node, duodenum and blood, and transcripts were detected for 6 of the 11 pseudogenes in some of these tissues.

Conclusions

In the present work we have characterized the ovine RPSA family. Our results have revealed the existence of 11 ovine RPSA pseudogenes and provide new data on their structure and sequence. Such information will facilitate molecular studies of the functional RPSA gene taking into account the existence of these pseudogenes in the design of experiments. It remains to be investigated if the transcribed members are functional as regulatory non-coding RNA or as functional proteins.
The Botrytis cinerea xylanase Xyn11A contributes to virulence with its necrotizing activity, not with its catalytic activity
Authors: Noda Judith , Brito Nélida , González Celedonio
Published: March 2010

Background

The Botrytis cinerea xylanase Xyn11A has been previously shown to be required for full virulence of this organism despite its poor contribution to the secreted xylanase activity and the low xylan content of B. cinerea hosts. Intriguingly, xylanases from other fungi have been shown to have the property, independent of the xylan degrading activity, to induce necrosis when applied to plant tissues, so we decided to test the hypothesis that secreted Xyn11A contributes to virulence by promoting the necrosis of the plant tissue surrounding the infection, therefore facilitating the growth of this necrotroph.

Results

We show here that Xyn11A has necrotizing activity on plants and that this capacity is conserved in site-directed mutants of the protein lacking the catalytic activity. Besides, Xyn11A contributes to the infection process with the necrotizing and not with the xylan hydrolyzing activity, as the catalytically-impaired Xyn11A variants were able to complement the lower virulence of the xyn11A mutant. The necrotizing activity was mapped to a 30-amino acids peptide in the protein surface, and this region was also shown to mediate binding to tobacco spheroplasts by itself.

Conclusions

The main contribution of the xylanase Xyn11A to the infection process of B. cinerea is to induce necrosis of the infected plant tissue. A conserved 30-amino acids region on the enzyme surface, away from the xylanase active site, is responsible for this effect and mediates binding to plant cells.
Adaptive regression modeling of biomarkers of potential harm in a population of U.S. adult cigarette smokers and nonsmokers
Authors: Warner John H , Liang Qiwei , Sarkar Mohamadi , Mendes Paul E , Roethig Hans J
Published: March 2010

Background

This article describes the data mining analysis of a clinical exposure study of 3585 adult smokers and 1077 nonsmokers. The analysis focused on developing models for four biomarkers of potential harm (BOPH): white blood cell count (WBC), 24 h urine 8-epi-prostaglandin F2α (EPI8), 24 h urine 11-dehydro-thromboxane B2 (DEH11), and high-density lipoprotein cholesterol (HDL).

Methods

Random Forest was used for initial variable selection and Multivariate Adaptive Regression Spline was used for developing the final statistical models

Results

The analysis resulted in the generation of models that predict each of the BOPH as function of selected variables from the smokers and nonsmokers. The statistically significant variables in the models were: platelet count, hemoglobin, C-reactive protein, triglycerides, race and biomarkers of exposure to cigarette smoke for WBC (R-squared = 0.29); creatinine clearance, liver enzymes, weight, vitamin use and biomarkers of exposure for EPI8 (R-squared = 0.41); creatinine clearance, urine creatinine excretion, liver enzymes, use of Non-steroidal antiinflammatory drugs, vitamins and biomarkers of exposure for DEH11 (R-squared = 0.29); and triglycerides, weight, age, sex, alcohol consumption and biomarkers of exposure for HDL (R-squared = 0.39).

Conclusions

Levels of WBC, EPI8, DEH11 and HDL were statistically associated with biomarkers of exposure to cigarette smoking and demographics and life style factors. All of the predictors togather explain 29%-41% of the variability in the BOPH.
Influence of maternal and perinatal factors on subsequent hospitalisation for asthma in children: evidence from the Oxford record linkage study
Authors: Davidson Rebekah , Roberts Stephen E , Wotton Clare J , Goldacre Michael J
Published: March 2010

Background

There is much interest in the possibility that perinatal factors may influence the risk of disease in later life. We investigated the influence of maternal and perinatal factors on subsequent hospital admission for asthma in children.

Methods

Analysis of data from the Oxford record linkage study (ORLS) to generate a retrospective cohort of 248 612 records of births between 1970 and 1989, with follow-up to records of subsequent hospital admission for 4 017 children with asthma up to 1999.

Results

Univariate analysis showed significant associations between an increased risk of admission for asthma and later years of birth (reflecting the increase in asthma in the 1970s and 1980s), low social class, asthma in the mother, unmarried mothers, maternal smoking in pregnancy, subsequent births compared with first-born, male sex, low birth weight, short gestational age, caesarean delivery, forceps delivery and not being breastfed. Multivariate analysis, identifying each risk factor that had a significant effect independently of other risk factors, confirmed associations with maternal asthma (odds ratio (OR) 3.1, 95% confidence interval 2.7-3.6), male sex (versus female, 1.8, 1.7-2.0), low birth weight (1000-2999 g versus 3000-3999 g, 1.2, 1.1-1.3), maternal smoking (1.1, 1.0-1.3) and delivery by caesarean section (1.2; 1.0-1.3). In those first admitted with asthma under two years old, there were associations with having siblings (e.g. second child compared with first-born, OR 1.3, 1.0-1.7) and short gestational age (24-37 weeks versus 38-41 weeks, 1.6, 1.2-2.2). Multivariate analysis confined to those admitted with asthma aged six years or more, showed associations with maternal asthma (OR 3.8, 3.1-4.7), age of mother (under 25 versus 25-34 at birth, OR 1.16, 1.03-1.31; over 35 versus 25-34, OR 1.4, 1.1-1.7); high social class was protective (1 and 2, compared with 3, 0.72; 0.63-0.82). Hospital admission for asthma in people aged over six was more common in males than females (1.4; 1.2-1.5); but, by the teenage years, the sex ratio reversed and admission was more common in females than males.

Conclusion

Several maternal characteristics and perinatal factors are associated with an elevated risk of hospital admission for asthma in the child in later life.
pEPito: a significantly improved non-viral episomal expression vector for mammalian cells
Authors: Haase Rudolf , Argyros Orestis , Wong Suet-Ping , Harbottle Richard P , Lipps Hans J , Ogris Manfred , Magnusson Terese , Pinto Maria G Vizoso , Haas Jürgen , Baiker Armin
Published: March 2010

Background

The episomal replication of the prototype vector pEPI-1 depends on a transcription unit starting from the constitutively expressed Cytomegalovirus immediate early promoter (CMV-IEP) and directed into a 2000 bp long matrix attachment region sequence (MARS) derived from the human β-interferon gene. The original pEPI-1 vector contains two mammalian transcription units and a total of 305 CpG islands, which are located predominantly within the vector elements necessary for bacterial propagation and known to be counterproductive for persistent long-term transgene expression.

Results

Here, we report the development of a novel vector pEPito, which is derived from the pEPI-1 plasmid replicon but has considerably improved efficacy both in vitro and in vivo. The pEPito vector is significantly reduced in size, contains only one transcription unit and 60% less CpG motives in comparison to pEPI-1. It exhibits major advantages compared to the original pEPI-1 plasmid, including higher transgene expression levels and increased colony-forming efficiencies in vitro, as well as more persistent transgene expression profiles in vivo. The performance of pEPito-based vectors was further improved by replacing the CMV-IEP with the human CMV enhancer/human elongation factor 1 alpha promoter (hCMV/EF1P) element that is known to be less affected by epigenetic silencing events.

Conclusions

The novel vector pEPito can be considered suitable as an improved vector for biotechnological applications in vitro and for non-viral gene delivery in vivo.
A portable automatic cough analyser in the ambulatory assessment of cough
Authors: Krajnik Malgorzata , Damps-Konstanska Iwona , Gorska Lucyna , Jassem Ewa
Published: March 2010

Background

Cough is one of the main symptoms of advanced lung disease. However, the efficacy of currently available treatment remains unsatisfactory. Research into the new antitussives requires an objective assessment of cough.

Methods

The aim of the study was to test the feasibility of a new automatic portable cough analyser and assess the correlation between subjective and objective evaluations of cough in 13 patients with chronic cough. The patients' individual histories, a cough symptom score and a numeric cough scale (1-10) were used as a subjective evaluation of cough and a computerized audio-timed recorder was used to measure the frequency of coughing.

Results

The pre-clinical validation has shown that an automated cough analyser is an accurate and reliable tool for the ambulatory assessment of chronic cough. In the clinical part of the experiment for the daytime, subjective cough scoring correlated with the number of all cough incidents recorded by the cough analyser (r = 0.63; p = 0.022) and the number of cough incidents per hour (r = 0.60; p = 0.03). However, there was no relation between cough score and the time spent coughing per hour (r = 0.48; p = 0.1). As assessed for the night-time period, no correlation was found between subjective cough scoring and the number of incidents per hour (r = 0.29; p = 0.34) or time spent coughing (r = 0.26; p = 0.4).

Conclusion

An automated cough analyser seems to be a feasible tool for the ambulatory monitoring of cough. There is a moderate correlation between subjective and objective assessments of cough during the daytime, whereas the discrepancy in the evaluation of night-time coughing might suggest that subjective analysis is unreliable.
Herbal mixtures in traditional medicine in Northern Peru
Authors: Bussmann Rainer W , Glenn Ashley , Meyer Karen , Kuhlman Alyse , Townesmith Andrew
Published: March 2010

The investigation of plant mixtures used in traditional medicine in Northern Peru yielded a total of 974 herbal preparations used to treat 164 different afflictions. Psychosomatic disorders were, with almost 30% of all recipes applied, the most important afflictions treated. In most cases, healers used only one or two mixtures to treat an illness. However, up to 49 different preparations were used to treat the same disease. This indicates a high degree of experimentation. Altogether 330 plant species, representing almost 65% of the medicinal flora used in the region were applied in mixtures. The overwhelming number of plant mixtures contained 2-7 different plant species, although in the most extreme case 27 distinct species were included. The cluster analysis confirmed that mixtures used for applications like inflammations, infections and blood purification, as well as cough, cold, bronchitis or other respiratory disorders, or urinary infection and kidney problems had similar floristic compositions. Mixtures used for nervous system disorders, anxiety and heart problems often had a similar composition
Interfacility transfers in a non-trauma system setting: an assessment of the Greek reality
Authors: Katsaragakis Stylianos , Drimousis Panagiotis G , Kleidi Eleftheria S , Toutouzas Kostas , Lapidakis Eleftherios , Papadakis Georgios , Daskalakis Kritolaos , Larentzakis Andreas , Theodoraki Maria E , Theodorou Dimitrios
Published: March 2010

Background

Quality assessment of any trauma system involves the evaluation of the transferring patterns. This study aims to assess interfacility transfers in the absence of a formal trauma system setting and to estimate the benefits from implementing a more organized structure.

Methods

The 'Report of the Epidemiology and Management of Trauma in Greece' is a one year project of trauma patient reporting throughout the country. It provided data concerning the patterns of interfacility transfers. We compared the transferred patient group to the non transferred patient group. Information reviewed included patient and injury characteristics, need for an operation, Intensive Care Unit (ICU) admittance and mortality. Analysis employed descriptive statistics and Chi-square test. Interfacility transfers were then assessed according to each health care facility's availability of five requirements; Computed Tomography scanner, ICU, neurosurgeon, orthopedic and vascular surgeon.

Results

Data on 8,524 patients were analyzed; 86.3% were treated at the same facility, whereas 13.7% were transferred. Transferred patients tended to be younger, male, and more severely injured than non transferred patients. Moreover, they were admitted to ICU more often, had a higher mortality rate but were less operated on compared to non transferred patients. The 34.3% of transfers was from facilities with none of the five requirements, whereas the 12.4% was from those with one requirement. Low level facilities, with up to three requirements transferred 43.2% of their transfer volume to units of equal resources.

Conclusion

Trauma management in Greece results in a high number of transfers. Patients are frequently transferred between low level facilities. Better coordination could lead to improved outcomes and less cost.
IgA anti-Actin antibodies in children with celiac disease: comparison of immunofluorescence with Elisa assay in predicting severe intestinal damage
Authors: Bazzigaluppi Elena , Parma Barbara , Tronconi Giulia M , Corsin Patrizia , Albarello Luca , Mora Stefano , Barera Graziano
Published: March 2010

Background

Previous studies have demonstrated that the presence of serum IgA antibodies against actin filaments (AAA) in patients with celiac disease (CD) is strongly associated with mucosal damage and severe degrees of villous atrophy.

The aims of the present study were (1) to verify the effectiveness of IgA-AAA in newly diagnosed CD patients in a clinical setting (2) to compare the immunofluorescence assay with ELISA assay; (3) to compare the correlation of our IgA anti-tissue transglutaminase antibodies (tTG-Ab) class with mucosal intestinal lesions.

Methods

90 patients underwent endoscopy and multiple biopsies for suspected CD on the basis of symptoms, in presence of positive tTG-Ab tests. Twenty biopsied and 25 not-biopsied subjects with negative tTG-Ab were tested as control groups.

IgA-AAA assays were performed by indirect immunofluorescence using rat epithelial intestinal cells, and by ELISA with a commercial kit. tTG-Ab assay was a radio-binding assay.

Intestinal specimens were collected by upper endoscopy and the histological study was done according to the Marsh's classification modified by Oberhuber (M/O). Auto-antibodies assays and histological evaluation have been performed blindly by skilled operators.

Results

CD diagnosis was confirmed in 82 patients (type I M/O in 2 patients, IIIA in 18 patients, IIIB in 29 patients and IIIC in 33 patients). Two patients with type 1 lesion in presence of positive tTG-Ab and abdominal complaints, started a gluten free diet.

The rate of IgA-AAA positivity (sensitivity) by IFI and ELISA in histologically proven celiac disease patients, were 5.5% and 25% patients in IIIA, 27.5% and 34.4% patients in IIIB, 78.8% and 75% in IIIC patients, respectively.

Patients with normal or nearly normal mucosa, regardless of tTG-Ab status, presented negative IgA-AAA IFI assay. On the other hand, 1 patient with normal mucosa but positive tTG-Ab, also presented positive IgA-AAA ELISA. All healthy non biopsied controls had negative IgA-AAA. tTG-Ab serum concentration was significantly correlated with more severe intestinal lesion (IIIB, IIIC M/O).

Conclusions

IgA-AAA may be undetectable in presence of severe mucosal damage. Histology is still necessary to diagnose celiac disease and IgA-AAA cannot be included in usual screening tests, because it has little to offer if compared to the well-established tTG-Ab.

IgA-AAA could be an adjunctive, very useful tool to support the diagnosis of CD in case of suboptimal histology, when the biopsy is to be avoided for clinical reasons, or in case of negative parents' consensus.
Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints
Authors: Angyal Adrienn , Egelston Colt , Kobezda Tamás , Olasz Katalin , László Anna , Glant Tibor T , Mikecz Katalin
Published: March 2010

Introduction

Inflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate arthritis. Herein, we investigated the role of joint-homing versus lymphoid organ-homing T cells in the development of proteoglycan-induced arthritis (PGIA), an autoimmune model of RA.

Methods

To identify T cells migrating to the joints before and during development of autoimmune arthritis, we transferred fluorescence-labeled T cells, along with antigen-presenting cells, from BALB/c mice with PGIA to naïve syngeneic severe combined immunodeficient (SCID) mice. We then monitored the recruitment of donor T cells in the ankle joints and joint-draining lymph nodes of the recipients using in vivo two-photon microscopy and ex vivo detection methods. To limit T-cell access to the joints, we selectively depleted T cells in the blood circulation by treatment with FTY720, an inhibitor of lymphocyte egress from lymphoid organs. Reduction of T cell presence in both lymphoid organs and blood was achieved by injection of donor cells from which T cells were removed prior to transfer. T and B cells were quantitated by flow cytometry, and antigen (PG)-specific responses were assessed by cell proliferation and serum antibody assays.

Results

Despite development of adoptively transferred arthritis in the recipient SCID mice, we found very few donor T cells in their joints after cell transfer. Treatment of recipient mice with FTY720 left the T-cell pool in the lymphoid organs intact, but reduced T cells in both peripheral blood and joints. However, FTY720 treatment failed to inhibit PGIA development. In contrast, arthritis was not seen in recipient mice after transfer of T cell-depleted cells from arthritic donors, and serum autoantibodies to PG were not detected in this group of mice.

Conclusions

Our results suggest that antigen-specific T cells, which home to lymphoid organs and provide help to B cells for systemic autoantibody production, play a greater role in the development and progression of autoimmune arthritis than the small population of T cells that migrate to the joints.
Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review
Authors: Dankbaar Jan W , Slooter Arjen JC , Rinkel Gabriel JE , Schaaf Irene C vander
Published: March 2010

Introduction

Triple-H therapy and its separate components (hypervolemia, hemodilution, and hypertension) aim to increase cerebral perfusion in subarachnoid haemorrhage (SAH) patients with delayed cerebral ischemia. We systematically reviewed the literature on the effect of triple-H components on cerebral perfusion in SAH patients.

Methods

We searched medical databases to identify all articles until October 2009 (except case reports) on treatment with triple-H components in SAH patients with evaluation of the treatment using cerebral blood flow (CBF in ml/100 g/min) measurement. We summarized study design, patient and intervention characteristics, and calculated differences in mean CBF before and after intervention.

Results

Eleven studies (4 to 51 patients per study) were included (one randomized trial). Hemodilution did not change CBF. One of seven studies on hypervolemia showed statistically significant CBF increase compared to baseline; there was no comparable control group. Two of four studies applying hypertension and one of two applying triple-H showed significant CBF increase, none used a control group. The large heterogeneity in interventions and study populations prohibited meta-analyses.

Conclusions

There is no good evidence from controlled studies for a positive effect of triple-H or its separate components on CBF in SAH patients. In uncontrolled studies, hypertension seems to be more effective in increasing CBF than hemodilution or hypervolemia.
The diagnostic value of serum leptin monitoring and its correlation with tumor necrosis factor-α in critically ill patients: a prospective observational study
Authors: Yousef Ayman Abd Al-Maksoud , Amr Yasser Mohamed , Suliman Ghada Abdulmomen
Published: March 2010

Introduction

Severe infection and sepsis are common causes of morbidity and mortality. Early diagnosis in critically ill patients is important to reduce these complications. The present study was conducted to determine the role of serum leptin at early diagnosis and differentiation between patients with manifestations of systemic inflammatory response syndrome (SIRS) and those with sepsis in patients suffering from a broad range of diseases in the intensive care unit (ICU) and its correlation with other biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).

Methods

One hundred and six adult ICU patients were observed. CRP, leptin, IL-6 and TNF-α were compared among the following groups: sepsis group (n = 40), SIRS group (n = 34) and non-SIRS group (n = 32). Patients were classified into these groups at the time of blood analysis for these biomarkers.

Results

Non-significant differences were observed among patients in different groups regarding biomarkers on the day of ICU admission. On the second day of ICU admission, significant elevation of leptin, IL-6 and TNF-α occurred in the SIRS and sepsis groups. Delayed elevation of CRP started on the fourth day of ICU admission in patients with sepsis. At the end of the first week, only CRP level was elevated in septic patients.

Conclusions

Serum leptin correlates well with serum level of IL-6 and TNF-α. Leptin helps to differentiate SIRS from non-SIRS patients. CRP is a classic marker of sepsis but is of late onset.
Eicosapentaenoic acid preserves diaphragm force generation following endotoxin administration
Authors: Supinski Gerald S , Vanags Jonas , Callahan Leigh Ann
Published: March 2010

Introduction

Infections produce severe respiratory muscle weakness, which contributes to the development of respiratory failure. An effective, safe therapy to prevent respiratory muscle dysfunction in infected patients has not been defined. This study examined the effect of eicosapentaenoic acid (EPA), an immunomodulator that can be safely administered to patients, on diaphragm force generation following endotoxin administration.

Methods

Rats were administered the following (n = 5/group): (a) saline, (b) endotoxin, 12 mg/kg IP, (c) endotoxin + EPA (1.0 g/kg/d), and (d) EPA alone. Diaphragms were removed and measurements made of the diaphragm force-frequency curve, calpain activation, caspase activation, and protein carbonyl levels.

Results

Endotoxin elicited large reductions in diaphragm specific force generation (P < 0.001), and increased diaphragm caspase activation (P < 0.01), calpain activation (P < 0.001) and protein carbonyl levels (P < 0.01). EPA administration attenuated endotoxin-induced reductions in diaphragm specific force, with maximum specific force levels of 27 ± 1, 14 ± 1, 23 ± 1, and 24 ± 1 N/cm2, respectively, for control, endotoxin, endotoxin + EPA, and EPA treated groups (P < 0.001). EPA did not prevent endotoxin induced caspase activation or protein carbonyl formation but significantly reduced calpain activation (P < 0.02).

Conclusions

These data indicate that endotoxin-induced reductions in diaphragm specific force generation can be partially prevented by administration of EPA, a nontoxic biopharmaceutical that can be safely given to patients. We speculate that it may be possible to reduce infection-induced skeletal muscle weakness in critically ill patients by administration of EPA.