bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification and characterization of cytochrome P450 monooxygenase genes in the ciliate Tetrahymena thermophila
Authors: Fu Chengjie , Xiong Jie , Miao Wei
Published: May 2009

Background

Cytochrome P450 monooxygenases play key roles in the metabolism of a wide variety of substrates and they are closely associated with endocellular physiological processes or detoxification metabolism under environmental exposure. To date, however, none has been systematically characterized in the phylum Ciliophora. T. thermophila possess many advantages as a eukaryotic model organism and it exhibits rapid and sensitive responses to xenobiotics, making it an ideal model system to study the evolutionary and functional diversity of the P450 monooxygenase gene family.

Results

A total of 44 putative functional cytochrome P450 genes were identified and could be classified into 13 families and 21 sub-families according to standard nomenclature. The characteristics of both the conserved intron-exon organization and scaffold localization of tandem repeats within each P450 family clade suggested that the enlargement of T. thermophila P450 families probably resulted from recent separate small duplication events. Gene expression patterns of all T. thermophila P450s during three important cell physiological stages (vegetative growth, starvation and conjugation) were analyzed based on EST and microarray data, and three main categories of expression patterns were postulated. Evolutionary analysis including codon usage preference, site-specific selection and gene-expression evolution patterns were investigated and the results indicated remarkable divergences among the T. thermophila P450 genes.

Conclusion

The characterization, expression and evolutionary analysis of T. thermophila P450 monooxygenase genes in the current study provides useful information for understanding the characteristics and diversities of the P450 genes in the Ciliophora, and provides the baseline for functional analyses of individual P450 isoforms in this model ciliate species.
Diversity of pneumococcal surface protein A (PspA) among prevalent clones in Spain
Authors: Rolo Dora , Ardanuy Carmen , Fleites Ana , Martín Rogelio , Liñares Josefina
Published: May 2009

Background

PspA is recognized as a major pneumococcal virulence factor and a possible vaccine candidate. The aim of this study was to analyze the PspA family and clade distribution among 112 Spanish pneumococci representatives of dominant clones among patients with invasive disease (n = 66) and nasopharyngeal healthy carriage in children (n = 46).

Results

PspA family 2 was predominant among invasive (63.6%) and carriage (54.3%) pneumococcal isolates. No PspA family 3 isolates were detected and only one strain was PspA negative. Although four clonal complexes contained strains of different clades, a clear association between clade and multi locus sequence typing results was found. Clades 1, 3 and 4 were associated with a wide variety of sequence types (ST) related to multiresistant and antibiotic-susceptible worldwide-disseminated clones. Clade 1 was associated with Spain6B-ST90, Spain14-ST18, Colombia5-ST289, Sweden1-ST306, Denmark14-ST230 and Sweden1-ST304 clones. Clade 3 was associated with Spain23F-ST81, Spain9V-ST156, Tennessee14-ST67, Netherlands3-ST180 and Netherlands7F-ST191 clones. Clade 4 was related to Sweden15A-ST63, Netherlands18C-ST113 and Greece21-ST193 clones. In contrast, PspA clade was not related to serotype, age or clinical origin of the isolates.

Conclusion

PspA clades were associated with genotypes. PspA family 2 and family 1 were dominant among major Spanish pneumococcal clones isolated from patients with invasive disease and nasopharyngeal carriage in children.
No effect of running and laboratory housing on adult hippocampal neurogenesis in wild caught long-tailed wood mouse
Authors: Hauser Thomas , Klaus Fabienne , Lipp Hans-Peter , Amrein Irmgard
Published: May 2009

Background

Studies of adult hippocampal neurogenesis (AHN) in laboratory rodents have raised hopes for therapeutic interventions in neurodegenerative diseases and mood disorders, as AHN can be modulated by physical exercise, stress and environmental changes in these animals. Since it is not known whether cell proliferation and neurogenesis in wild living mice can be experimentally changed, this study investigates the responsiveness of AHN to voluntary running and to environmental change in wild caught long-tailed wood mice (Apodemus sylvaticus).

Results

Statistical analyses show that running had no impact on cell proliferation (p = 0.44), neurogenesis (p = 0.94) or survival of newly born neurons (p = 0.58). Likewise, housing in the laboratory has no effect on AHN. In addition, interindividual differences in the level of neurogenesis are not related to interindividual differences of running wheel performance (rs = -0.09, p = 0.79). There is a correlation between the number of proliferating cells and the number of cells of neuronal lineage (rs = 0.63, p < 0.001) and the number of pyknotic cells (rs = 0.5, p = 0.009), respectively.

Conclusion

Plasticity of adult neurogenesis is an established feature in strains of house mice and brown rats. Here, we demonstrate that voluntary running and environmental changes which are effective in house mice and brown rats cannot influence AHN in long-tailed wood mice. This indicates that in wild long-tailed wood mice different regulatory mechanisms act on cell proliferation and neurogenesis. If this difference reflects a species-specific adaptation or a broader adaptive strategy to a natural vs. domestic environment is unknown.
A Schistosoma japonicumchimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens
Authors: Xu Xindong , Zhang Dongmei , Sun Wei , Zhang Qingfeng , Zhang Jingjing , Xue Xiangyang , Shen Luhui , Pan Weiqing
Published: May 2009

Background

Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4) via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice.

Methods

The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3+CD8-IFN-γ+cells and CD3+CD8-IL-4+cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge.

Results

Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced a significant reduction in liver egg deposition at 47.0–50.3% and the number of liver eggs per female at 34.5–37.2% but less effect on worm burdens at only 17.3–23.1%, whereas no effect of the formulations with other adjuvants on the number of liver eggs per female was observed.

Conclusion

Construction of polyvalent subunit vaccine was capable to enhance immunogenicity and protection efficacy against schistosomiasis. There was correlation of the polarized Th1 response with reduction of liver egg burdens, supporting the immune deviation strategy for schistosomiasis japonica vaccine development.
Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency
Authors: Louvel Murielle , Marcu Mariana , Trivin Christine , Souberbielle Jean-Claude , Brauner Raja
Published: May 2009

Background

Most patients with childhood non-organic growth hormone (GH) deficiency (GHD) produce a normal GH peak as young adults. Our objectives were to better define this transient GHD and evaluate the factors influencing the growth response of patients with pituitary stalk interruption syndrome (PSIS).

Methods

We studied 72 prepubertal patients with a GH peak < 6.7 ng/ml after 2 stimulation tests, treated with 0.2 mg GH/kg/w for at least 3 years. Group 1 (n = 53, 4.7 ± 4.0 years) had PSIS and Group 2 (n = 19, 9.2 ± 3.0 years) had transient GHD and normal pituitary.

Results

At diagnosis, 64% of Group 1 and one Group 2 were < 5 years old. The growth rate of 59% Group 1 and two Group 2 patients was ≤ -2 SDS. The GH peak of 64% Group 1 patients and no Group 2 patients was < 3 ng/ml. The plasma insulin-like growth factor-1 of all Group 1 and all but one Group 2 patients was ≤ -2 z scores.

During the first year of GH treatment, the growth rate was ≥ 2 SDS in 81% Group 1 and 37% Group 2 patients. In Group 1, it was negatively correlated with the GH peak before treatment (P < 0.03), and with the difference between the target and adult heights (P < 0.01).

The height gain SDSs between diagnosis and adult height were 1.7 ± 1.2 in Group 1 (n = 30) and 1.08 ± 0.8 in Group 2 (n = 12, P = 0.05).

Conclusion

The factors of the growth response to GH treatment should be analysed separately for each population: with and without PSIS or other markers.
Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis
Authors: Plum Stacy M , Park Eun J , Strawn Steve J , Moore Elizabeth G , Sidor Carolyn F , Fogler William E
Published: May 2009

Background

A critical component of disease progression in rheumatoid arthritis (RA) involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2) is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA) model.

Methods

Severe polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 μg of LPS (E. colistrain 0111:B4) via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily), or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining). In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d.vsq.w.vsq.w. × 2) were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis.

Results

Mice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21), blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of the study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2.

Conclusion

These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.
PTools: an opensource molecular docking library
Authors: Saladin Adrien , Fiorucci Sébastien , Poulain Pierre , Prévost Chantal , Zacharias Martin
Published: May 2009

Background

Macromolecular docking is a challenging field of bioinformatics. Developing new algorithms is a slow process generally involving routine tasks that should be found in a robust library and not programmed from scratch for every new software application.

Results

We present an object-oriented Python/C++ library to help the development of new docking methods. This library contains low-level routines like PDB-format manipulation functions as well as high-level tools for docking and analyzing results. We also illustrate the ease of use of this library with the detailed implementation of a 3-body docking procedure.

Conclusion

The PTools library can handle molecules at coarse-grained or atomic resolution and allows users to rapidly develop new software. The library is already in use for protein-protein and protein-DNA docking with the ATTRACT program and for simulation analysis. This library is freely available under the GNU GPL license, together with detailed documentation.
Structural insights into chondroitin sulphate A binding Duffy-binding-like domains from Plasmodium falciparum: implications for intervention strategies against placental malaria
Authors: Gill Jasmita , Chitnis Chetan E , Sharma Amit
Published: May 2009

Background

Placental malaria is typified by selective clustering of Plasmodium falciparum in the intervillous blood spaces of the placenta. Sequestration of malaria parasite in the human placenta is mediated by interactions between chondroitin sulphate A (CSA) on the syncytiotrophoblasts and proteins expressed on the surface of infected human erythrocytes. Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) encoded by the var2CSA gene is believed to be the main parasite ligand for CSA-mediated placental binding.

Methods

Extensive sequence and structure comparisons of the various CSA-binding and non-binding DBL domains from the var2CSA gene from A4 and 3D7 strains of P. falciparum were performed. Three-dimensional structural models of various DBL domains were built and analysed with a view to assessing conservation of CSA interaction sites across various DBL domains.

Results

Each of the six DBL domains from var2CSA are likely to retain the disulfide linkages evident from previously published DBL domain crystal structures. The number of disulfide linkages between the various DBL domains analysed varies from three to seven, of which two are conserved across all DBL domains. The conserved disulfide linkages are distributed within the respective three sub-domains and only one linkage is shared by sub-domains I and II. Major differences between CSA-binding DBL domains are in the loop regions, which tie the alpha helices together, and in variable length terminal extensions. Intriguingly, a crucial loop from A4 DBL 3X which provides the important Gly and Lys residues that chelate the bound sulphate is missing or significantly altered in all other DBL domains that interact with CSA. Further analysis of the proposed sulphate and predicted CSA-binding site indicates either none or very low level of conservation among the critical interacting residues.

Conclusion

Structural comparisons of the three-dimensional structures of CSA-binding DBL domains indicates that the proposed CSA interaction site on A4 DBL 3X is unlikely to be conserved across the other CSA-binding DBL domains from var2CSA. Therefore, the 4 CSA-binding DBL domains encoded by var2CSA are unlikely to have common architectures to their CSA recognition sites. These structural insights have clear implications in using CSA-binding DBL domains for vaccines against placental malaria as it is proposed that the various CSA-binding DBL domains on var2CSA will recognize their CSA ligands differently.
Preliminary study of malaria incidence in Nouakchott, Mauritania
Authors: Lekweiry Khadijetou Mint , Abdallahi Mohamed Ould , Ba Hâmpaté , Arnathau Céline , Durand Patrick , Trape Jean-François , Salem Ali Ould Mohamed
Published: May 2009

Background

Malaria is one of the main motives for outpatient consultation and hospitalization in Mauritania. However, its incidence remains unclear because of diagnostic problems and insufficient epidemiological data.

Methods

Between April and August 2007, a study on malaria incidence was carried out in Nouakchott city. A total of 237 febrile outpatients, from all Nouakchott districts, attending the two main hospitals of the city were investigated. Finger prick and blood dried filter paper samples were performed to prepare thick and thin films and nested-PCR for malaria parasite species identification and density. The accuracy of diagnosis of 'presumptive malaria', assigned by clinicians and based on fever and other malaria suggestive symptoms, was assessed. Entomological investigations based on morphological and molecular characterization of Anopheline species were conducted in Dar Naïm district.

Results

Malaria prevalence rate was 25.7% (61/237), the majority of positive blood slides as well as nested-PCR products were due to Plasmodium vivax 70.5% (43/61) and Plasmodium ovale 24.6% (15/61). Two malaria patients, both with P. vivax, have never travelled out of Nouakchott and seem likely to have been autochthonous (3.3%). Of the 237 individuals included in the survey, 231(97.5%) were clinically diagnosed and treated as malaria cases. 26.4% of clinically diagnosed cases were positive for Plasmodium using microscopic examination and PCR. Thus, false positive cases constituted 73.6% (170/231) of the clinically diagnosed malaria cases. The search for mosquito vectors in Dar Naïm district allowed morphological and molecular identification of Anopheles arabiensis and Anopheles pharoensis.

Conclusion

This study demonstrates that, during the hot and dry season, Plasmodium species responsible of recurrent malaria (P. vivax and P. ovale) are the dominant species in Nouakchott city and autochthonous malaria cases exist but are rare. Clinical diagnosis of malaria has a very low positive predicted value. The systematic use of microscopy-based diagnosis and/or rapid diagnostic tests should be considered to appropriately manage malaria and non-malaria cases.
Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages
Authors: Sarir Hadi , Mortaz Esmaeil , Karimi Khalil , Kraneveld Aletta D , Rahman Irfan , Caldenhoven Eric , Nijkamp Frans P , Folkerts Gert
Published: May 2009

Background

Toll-like receptors (TLRs) are present on monocytes and alveolar macrophages that form the first line of defense against inhaled particles. The importance of those cells in the pathophysiology of chronic obstructive pulmonary disease (COPD) has well been documented. Cigarette smoke contains high concentration of oxidants which can stimulate immune cells to produce reactive oxygen species, cytokines and chemokines.

Methods

In this study, we evaluated the effects of cigarette smoke medium (CSM) on TLR4 expression and interleukin (IL)-8 production by human macrophages investigating the involvement of ROS.

Results and Discussion

TLR4 surface expression was downregulated on short term exposure (1 h) of CSM. The downregulation could be explained by internalization of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and protein were also increased by CSM. CSM stimulation increased intracellular ROS-production and decreased glutathione (GSH) levels. The modulation of TLR4 mRNA and surface receptors expression, IRAK activation, IκB-α degradation, IL-8 mRNA and protein, GSH depletion and ROS production were all prevented by antioxidants such as N-acetyl-L-cysteine (NAC).

Conclusion

TLR4 may be involved in the pathogenesis of lung emphysema and oxidative stress and seems to be a crucial contributor in lung inflammation.
Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial
Authors: Beran Jiri , Ambrozaitis Arvydas , Laiskonis Alvydas , Mickuviene Narseta , Bacart Patrick , Calozet Yvan , Demanet Etienne , Heijmans Stephane , Van Belle Paul , Weber Françoise , Salamand Camille
Published: May 2009

Background

Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.

Methods

In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.

Results

In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.

Conclusion

An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.

Trial registration

Clinicaltrials.gov NCT00703651.
Activation of Cytosolic Phospholipase A2 in Dorsal Root Ganglion Neurons by Ca2+/Calmodulin-Dependent Protein Kinase II after Peripheral Nerve Injury
Authors: Hasegawa Shigeo , Kohro Yuta , Tsuda Makoto , Inoue Kazuhide
Published: May 2009

Background

Peripheral nerve injury leads to a persistent neuropathic pain state in which innocuous stimulation elicits pain behavior (tactile allodynia), but the underlying mechanisms have remained largely unknown. We have previously shown that spinal nerve injury induces the activation of cytosolic phospholipase A2 (cPLA2) in injured dorsal root ganglion (DRG) neurons that contribute to tactile allodynia. However, little is known about the signaling pathway that activates cPLA2 after nerve injury. In the present study, we sought to determine the mechanisms underlying cPLA2 activation in injured DRG neurons in an animal model of neuropathic pain, focusing on mitogen-activated protein kinases (MAPKs) and Ca2+/calmodulin-dependent protein kinase II (CaMKII).

Results

Pharmacological inhibition of either p38 or extracellular signal-regulated kinase (ERK) in the injured DRG, which led to suppression of the development of tactile allodynia, did not affect cPLA2 phosphorylation and translocation after nerve injury. By contrast, a CaMKII inhibitor prevented the development and expression of nerve injury-induced tactile allodynia and reduced both the level of cPLA2 phosphorylation and the number of DRG neurons showing translocated cPLA2 in response to nerve injury. Applying ATP to cultured DRG neurons increased the level of both phosphorylated cPLA2 and CaMKII in the vicinity of the plasma membrane and caused physical association of these two proteins. In addition, ATP-stimulated cPLA2 and CaMKII phosphorylation were inhibited by both a selective P2X3R/P2X2+3R antagonist and a nonselective voltage-dependent Ca2+ channel (VDCC) blocker.

Conclusion

These results suggest that CaMKII, but not MAPKs, has an important role in cPLA2 activation following peripheral nerve injury, probably through P2X3R/P2X2+3R and VDCCs in primary afferent neurons.
The Inventory of Personality Organisation: its psychometric properties among student and clinical populations in Japan
Authors: Igarashi Hiromi , Kikuchi Hiroyoshi , Kano Rikihachiro , Mitoma Hiroshi , Shono Masahiro , Hasui Chieko , Kitamura Toshinori
Published: May 2009

Background

The Inventory of Personality Organisation (IPO) is a self-report measure that reflects personality traits, as theorised by Kernberg.

Methods

In study 1, the Japanese version of the IPO was distributed to a population of Japanese university students (N = 701). The students were randomly divided into two groups. The factor structure derived from an exploratory factor analysis among one subsample was tested using a confirmatory factor structure among another subsample. In study 2, the factor-driven subscales of the IPO were correlated with other variables that would function as external criteria to validate the scale in a combined population of the students used in study 1 and psychiatric outpatients (N = 177).

Results

In study 1 the five-factor structure presented by the original authors was replicated in exploratory factor analyses in one subgroup of students. However, this was through reduction of the number of items (the number of the primary items was reduced from 57 to 24 whereas the number of the additional items was reduced from 26 to 13) due to low endorsement frequencies as well as low factor loadings on a designated factor. The new factor structure was endorsed by a confirmatory factor analysis in the other student subgroup. In study 2 the new five subscales of the Japanese IPO were likely to be correlated with younger age, more personality psychopathology (borderline and narcissistic), more dysphoric mood, less psychological well-being, more insecure adult attachment style, lower self-efficacy, and more frequent history of childhood adversity. The IPO scores were found to predict the increase in suicidal ideation in a week's time in a longitudinal follow-up.

Conclusion

Although losing more than 40% of the original items, the Japanese IPO may be a reliable and valid measure of Kernberg's personality organisation for Japanese populations.
Ethnomedical survey of Berta ethnic group Assosa Zone, Benishangul-Gumuz regional state, mid-west Ethiopia
Authors: Flatie Teferi , Gedif Teferi , Asres Kaleab , Gebre-Mariam Tsige
Published: May 2009

Traditional medicine (TM) has been a major source of health care in Ethiopia as in most developing countries around the world. This survey examined the extent and factors determining the use of TM and medicinal plants by Berta community. One thousand and two hundred households (HHs) and fourteen traditional healers were interviewed using semi-structured questionnaires and six focused group discussions (FGDs) were conducted. The prevalence of the use of TM in the two weeks recall period was 4.6%. The HH economic status was found to have a significant effect while the educational level and age of the patients have no effect either on the care seeking behavior or choice of care. Taking no action about a given health problem and using TM are common in females with low-income HHs. Forty plant species belonging to 23 families were reported, each with local names, methods of preparation and parts used. This study indicates that although the proportion of the population that uses TM may be small it is still an important component of the public health care in the study community as complementary and alternative medicine.
Class-switched B cells display response to therapeutic B-cell depletion in rheumatoid arthritis
Authors: Möller Burkhard , Aeberli Daniel , Eggli Stefan , Fuhrer Martin , Vajtai Istvan , Vögelin Esther , Ziswiler Hans-Rudolf , Dahinden Clemens A , Villiger Peter M
Published: May 2009

Introduction

Reconstitution of peripheral blood (PB) B cells after therapeutic depletion with the chimeric anti-CD20 antibody rituximab (RTX) mimics lymphatic ontogeny. In this situation, the repletion kinetics and migratory properties of distinct developmental B-cell stages and their correlation to disease activity might facilitate our understanding of innate and adaptive B-cell functions in rheumatoid arthritis (RA).

Methods

Thirty-five 'RTX-naïve' RA patients with active arthritis were treated after failure of tumour necrosis factor blockade in an open-label study with two infusions of 1,000 mg RTX. Prednisone dose was tapered according to clinical improvement from a median of 10 mg at baseline to 5 mg at 9 and 12 months. Conventional disease-modifying antirheumatic drugs were kept stable. Subsets of CD19+ B cells were assessed by flow cytometry according to their IgD and CD27 surface expression. Their absolute number and relative frequency in PB were followed every 3 months and were determined in parallel in synovial tissue (n = 3) or synovial fluid (n = 3) in the case of florid arthritis.

Results

Six of 35 patients fulfilled the European League Against Rheumatism criteria for moderate clinical response, and 19 others for good clinical response. All PB B-cell fractions decreased significantly in number (P < 0.001) after the first infusion. Disease activity developed independently of the total B-cell number. B-cell repopulation was dominated in quantity by CD27-IgD+ 'naïve' B cells. The low number of CD27+IgD- class-switched memory B cells (MemB) in the blood, together with sustained reduction of rheumatoid factor serum concentrations, correlated with good clinical response. Class-switched MemB were found accumulated in flaring joints.

Conclusions

The present data support the hypothesis that control of adaptive immune processes involving germinal centre-derived, antigen, and T-cell-dependently matured B cells is essential for successful RTX treatment.
Dissecting the physiological role of selective transmembrane-segment retention at the ER translocon
Authors: Cross Benedict C. S. , High Stephen
Published: May 2009

The membrane integration of polytopic proteins is coordinated at the endoplasmic reticulum (ER) by the conserved Sec61 translocon, which facilitates the lateral release of transmembrane (TM) segments into the lipid phase during polypeptide translocation. Here we use a site-specific crosslinking strategy to study the membrane integration of a new model protein and show that the TM segments of the P2X2 receptor are retained at the Sec61 complex for the entire duration of the biosynthetic process. This extremely prolonged association implicates the Sec61 complex in the regulation of the membrane integration process, and we use both in vitro and in vivo analyses to study this effect further. TM-segment retention depends on the association of the ribosome with the Sec61 complex, and complete lateral exit of the P2X2 TM segments was only induced by the artificial termination of translation. In the event of the premature release of P2X2 TM1 from the ER translocon, the truncated polypeptide fragment was to found aggregate in the ER membrane, suggesting a distinct physiological requirement for the delayed release of TM segments from the ER translocon site.
Fission yeast Tor1 functions as part of TORC1 to control mitotic entry through the stress MAPK pathway following nutrient stress
Authors: Hartmuth Sonya , Petersen Janni
Published: May 2009

TOR signalling coordinates growth and division to control cell size. Inhibition of Schizosaccharomyces pombe Tor1, in response to a reduction in the quality of the nitrogen source (nutrient stress), promotes mitotic onset through activation of the mitogen-activated protein kinase (MAPK) Sty1 (also known as Spc1). Here we show that `nutrient starvation' (complete withdrawal of nitrogen or leucine) blocks mitotic commitment by altering Sty1 signalling and that different degrees of Sty1 activation determine these differences in mitotic commitment decisions. Mammals contain one TOR kinase, whereas yeasts contain two. In each case, they comprise two distinct complexes: TORC1 and TORC2. We find that nutrient-stress-induced control of mitotic onset, through Tor1, is regulated through changes in TORC1 signalling. In minimal medium, Tor1 interacts with the TORC1 component Mip1 (raptor), and overexpression of tor1+ generates growth defects reminiscent of TORC1 mutants. Strains lacking the TORC2-specific components Sin1 and Ste20 (rictor) still advance mitotic onset in response to nutrient stress. By contrast, Mip1 and the downstream effector Gad8 (a S6K kinase homologue), like Tor1, are essential for nutrient stress to advance mitotic onset. We conclude that S. pombe Tor1 and Tor2 can both act in TORC1. However, it is the inhibition of Tor1 as part of TORC1 that promotes mitosis following nutrient stress.
Real-time fault diagnostic system for a steam turbine generator set by using a fuzzy cerebellar model articulation controller
Authors: Yan C , Zhang H , Peng D , Li H , Yang L
Published: May 2009

Because a serious fault would result in a reduced amount of electricity supply in a power plant, the real-time fault diagnosis system is extremely important for a steam turbine generator set. A novel real-time intelligent fault diagnosis system is proposed by using a fuzzy cerebellar model articulation controller (CMAC) neural network to detect and identify the faults and failures of critical components. A framework of the fault diagnosis system is described. The model of a novel fault diagnosis system by using a fuzzy CMAC is built and analysed in detail step by step. A case of the diagnosis including three faults is simulated with a fuzzy CMAC. The results show that the real-time fault diagnostic system is of high accuracy, quick convergence, and high noise rejection. Moreover, the model is verified by two examples. It is found that this model is feasible. Finally, the effects of the generalization parameter and address number in fault diagnosis are discussed.
A method of multiobjective optimization using a genetic algorithm and an artificial immune system
Authors: Park H , Kwak N-S , Lee J
Published: May 2009

The immune system has pattern recognition capabilities based on reinforced learning, memory, and affinity maturation interacting between antigens (Ags) and antibodies (Abs). This article deals with an adaptation of artificial immune system (AIS) into genetic-algorithm (GA)-based multi-objective optimization. The present study utilizes the pattern recognition from an AIS and the evolution from a GA. Using affinity measures between Ags and Abs, GA-based immune simulation discovers a generalist Ab that represents the common pattern among Ags. Non-dominated Pareto-optimal solutions are obtained via GA-based immune simulation in which dominated designs are considered as Ags, whereas non-dominated designs are assigned to Abs. This article discusses the procedure of identifying Pareto-optimal solutions through the immune system-based pattern recognition. A number of mathematical function problems that are described by discontinuity or disconnection in the shape of Pareto surface are first examined as test examples. Subsequently, engineering optimization problems such as rotating flywheel disc and ten-bar planar truss are explored to support the present study.
Assessment of combustion in natural gas dual-fuelled compression ignition engines with dimethyl ether and rapeseed methyl ester pilot ignition
Authors: Namasivayam A M , Crookes R J , Korakianitis T , Olsen J
Published: May 2009

Compression-ignition engines are known to be more efficient than similar-sized spark-ignition engines because of the higher compression ratios and leaner combustion. The emissions of soot and nitrogen oxides remain the main hurdle in the complete exploitation of these engines. Dual-fuelling is one means favoured for solving the emission problem, in which high-octane fuels are used as the main fuel which is ignited by a smaller pilot injection of diesel or another high-cetane fuel. These dual-fuel engines produce less particulate matter and nitrogen oxides than spark-ignition engines, while retaining the desired compression-ignition engine efficiency. In the present investigation, tests were conducted using a variety of renewable and non-renewable fuels for pilot injection. The pilot fuels employed were conventional diesel, rapeseed methyl ester (known as biodiesel), and dimethyl ether, while natural gas was used as the main fuel. Biogas, or landfill gas, would be the renewable alternative. Pressure versus crank angle traces were obtained, together with their first and second derivatives. These were analysed to determine the crank angle at which ignition began. Diagrams that show the rate of reaction were also plotted for the same purpose. Here, the start of ignition is determined by the trace suddenly changing slope and rising above zero. Using these methods, the ignition delay was determined for different operating conditions and comparisons drawn for different pilot fuels. The characteristic shapes of rate-of-reaction curves were analysed highlighting differences in the combustion processes occurring in single- and dual-fuel diesel engine operation. Emissions data for different operating conditions were also obtained and analysed, showing a tendency for lower emissions of smoke and oxides of nitrogen but increased carbon monoxide and unburnt hydrocarbons to be produced in dual-fuelling. Carbon dioxide was also reduced.
Resource-Limited Multiattribute Value Analysis of Alternatives for Immobilizing Radioactive Liquid Process Waste Stored in Saluggia, Italy
Authors: Brothers Alan J. , Mattigod Shas V. , Strachan Denis M. , Beeman Gordon H. , Kearns Paul K. , Papa Angelo , Monti Carlo
Published: May 2009

This large Italian public works project started with the development of engineering data to support the evaluation of three alternatives for processing nuclear waste. After an analysis of the alternatives' performance from an engineering perspective was completed, Società Gestione Impianti Nucleari (Sogin), which is the Italian authority with the responsibility to decommission Italy's four nuclear power plants, asked Battelle, a company thoroughly familiar with nuclear waste processing, to provide an independent assessment of this important decision. The initial analysis did not include an evaluation of alternative performance from the perspective of a broad set of public values. As part of the assessment, we developed a decision methodology as a practical variation of the data-intensive decision processes often found in textbooks. In this paper, we describe a decision process in which we made use of engineering data and expert judgment to minimize expensive additional data collection so that we could perform a multiattribute decision analysis that was theoretically grounded and economical to implement, while incorporating both engineering and stakeholder objectives. Through this process, the Battelle staff verified the initial selection made by the staff at Sogin.
Visual and Computer Software-Aided Estimates of Dupuytren'ss Contractures: Correlation with Clinical Goniometric Measurements
Authors: Smith RP , Dias JJ , Ullah A , Bhowal B
Published: May 2009

INTRODUCTION

Corrective surgery for Dupuytren's disease represents a significant proportion of a hand surgeon's workload. The decision to go ahead with surgery and the success of surgery requires measuring the degree of contracture of the diseased finger(s). This is performed in clinic with a goniometer, pre- and postoperatively. Monitoring the recurrence of the contracture can inform on surgical outcome, research and audit.

PATIENTS AND METHODS

We compared visual and computer software-aided estimation of Dupuytren's contractures to clinical goniometric measurements in 60 patients with Dupuytren's disease. Patients' hands were digitally photographed. There were 76 contracted finger joints – 70 proximal interphalangeal joints and six distal interphalangeal joints. The degrees of contracture of these images were visually assessed by six orthopaedic staff of differing seniority and re-assessed with computer software.

RESULTS

Across assessors, the Pearson correlation between the goniometric measurements and the visual estimations was 0.83 and this significantly improved to 0.88 with computer software. Reliability with intra-class correlations achieved 0.78 and 0.92 for the visual and computer-aided estimations, respectively, and with test–retest analysis, 0.92 for visual estimation and 0.95 for computer-aided measurements.

CONCLUSIONS

Visual estimations of Dupuytren's contractures correlate well with actual clinical goniometric measurements and improve further if measured with computer software. Digital images permit monitoring of contracture after surgery and may facilitate research into disease progression and auditing of surgical technique.
Improving the Provision of Carotid Endarterectomy in Line with UK Government Targets Requires More than Just Motivated Surgeons
Authors: Brown Claire , Naylor A Ross
Published: May 2009

INTRODUCTION

Carotid endarterectomy confers maximum benefit in symptomatic patients provided it is performed within < 2 weeks of presentation, but few centres achieve this target. The objective of this study was to determine if a surgeon with an interest in carotid endarterectomy could make simple modifications to practice so that carotid endarterectomy was performed within 2 weeks of referral in the majority of patients.

PATIENTS AND METHODS

Audit of 44 symptomatic patients undergoing carotid endarterectomy by one surgeon in 2007 after implementing simple changes in practice (e.g. ad hoc cancellation of non-urgent cases, ad hoc utilisation of cancelled theatre sessions). Outcomes were compared with 36 symptomatic patients undergoing carotid endarterectomy in 2006.

RESULTS

There was only a modest reduction in delay to surgery. In 2006, 11% underwent carotid endarterectomy within 2 weeks of referral increasing to 20% in 2007. By 2007, 48% underwent surgery within 4 weeks compared with 33% in 2006.

CONCLUSIONS

Notwithstanding the additional impact of delays from symptom onset to referral, achieving a 2-week target will require more than motivated surgeons making simple changes to practice. It seems inevitable that vascular units will have to identify 1–2 ‘ring fenced’ theatre sessions per week (but some could go unused) and surgeons will have to accept that they may not always operate on the patients they work-up.
Surgeons' Experience of Learning Psychological Skills: A Preliminary Evaluation of a Psychological Skills Training Course
Authors: Mason Victoria , Balloo Selina , Upton Dominic , Heer Kamal , Higton Phil , Shiralkar Uttam
Published: May 2009

INTRODUCTION

A range of human factors have been shown to impact on surgical performance although little is known about the impact of training on the views of surgeons towards these factors or how receptive surgeons are to such training.

SUBJECTS AND METHODS

This was an observational pilot study using a short questionnaire designed to elicit views of surgeons towards a range of human factors prior to, and immediately following, a course designed to address human factors in surgical performance. Focus groups were also conducted before and immediately after the course to elicit views.

RESULTS

Of all the human factors assessed, decision-making was rated on a visual analogue scale as having the biggest impact on performance both before and after the course. In general, views of human factors changed following the course, most notably an increase in the extent to which work stress, interpersonal difficulties and personality were believed to affect performance. Three themes emerged from the focus groups: (i) personal professional development; (ii) the relationship between trainer and trainee; and (iii) the changing perspective.

CONCLUSIONS

Surgeons from a range of specialties are receptive to training on the impact of human factors on performance and this study has shown that views may change following a course designed to address this. Further training to address the theory–practice gap is warranted in addition to an evaluation of its effectiveness.
Does the Number of Trauma Lists Provided Affect Care and Outcome of Patients with Fractured Neck of Femur?
Authors: Kalson NS , Mulgrew E , Cook G , Lovell ME
Published: May 2009

INTRODUCTION

Delay in surgery for fractured neck of femur is associated with increased mortality; it is recommended that patients with fractured neck of femur are operated within 48 h. North West hospitals provide dedicated trauma lists, as recommended by the British Orthopaedic Association, to allow rapid access to surgery. We investigated trauma list provision by each trust and its effects on the time taken to get neck of femur patients to surgery and patient survival.

PATIENTS AND METHODS

The number of trauma lists provided by 13 acute trusts was determined by telephone interview with the theatre manager. Data on operating delays, reasons for delay and 30-day mortality were obtained from the Greater Manchester and Wirral fractured neck of femur audit.

RESULTS

A total of 883 patients were included in the audit (35–126 per hospital). Overall, 5–15 trauma lists were provided each week, and 80% of lists were consultant-led. Of patients, 31.8% were operated on within 24 h and 36.9% were delayed more than 48 h; 37.7% of delays were for non-medical reasons. The 30-day mortality rates varied between 5–19% (mean, 11.8%). There were no significant relationships between the number of trauma lists and these variables. When divided into hospitals with > 10 lists per week (n = 6) and those with < 10 lists per week (n = 7) there were no significant differences in 48-h delay, non-medical delay or mortality. However, 24-h delay showed a trend to be lower in those with > 10 lists (34.6% of patients versus 28.9%; P = 0.09).

CONCLUSIONS

Most trusts provided at least one dedicated daily list. This study shows that extra lists may enable trusts to cope better with fractured neck of femur but do not change mortality.