bluuebunny/crossref_metadata_2025 huggingface dataset:
Repair versus Reconstruction of the Fibular Collateral Ligament and Posterolateral Corner in the Multiligament-Injured Knee
Authors: Levy Bruce A. , Dajani Khaled A. , Morgan Joseph A. , Shah Jay P. , Dahm Diane L. , Stuart Michael J.
Published: February 2010

Background

Treatment of the multiligament-injured knee remains controversial.

Purpose

To compare clinical and functional outcomes of a consecutive series of multiligament-injured knees that underwent repair of the fibular collateral ligament (FCL) and posterolateral corner (PLC), followed by delayed cruciate ligament reconstructions, with those that had single-stage multiligament reconstruction.

Study Design

Cohort study; Level of evidence, 3.

Methods

Patients with multiligament knee injury treated by a single surgeon were identified in our prospective database. Between February 2004 and May 2005, patients underwent repair of medial- and lateral-sided injuries, followed by delayed cruciate ligament reconstructions. Between May 2005 and February 2007, patients underwent single-stage multiligament knee reconstruction. All patients followed a standard rehabilitation protocol. Inclusion criteria were minimum 2-year follow-up and multiligament knee injury including the FCL/PLC. International Knee Documentation Committee subjective and Lysholm scores and objective clinical data were documented.

Results

We identified 45 knees (42 patients); 17 knees (14 patients) were excluded, leaving 28 knees (28 patients) in the study. The repair/staged group (10 knees in 10 patients) had a mean follow-up of 34 months (range, 24-49 months). The reconstruction group (18 knees in 18 patients) had a mean follow-up of 28 months (range, 24-41 months). Four of the 10 FCL/PLC repairs (40%) and 1 of the 18 FCL/PLC reconstructions (6%) failed (P = .04). After revision reconstructions, there were no statistically significant differences between mean International Knee Documentation Committee subjective scores (79 vs. 77, P = .92) and mean Lysholm scores (85 vs 88, P = .92). Regression analysis showed no effect on failure based on age, sex, injury mechanism, time to surgery, interval between stages, total number of ligaments injured, or location of tear.

Conclusion

Our series demonstrated a statistically significant higher rate of failure for repair compared with reconstruction of the FCL/PLC. Reconstruction of the FCL/PLC structures is a more reliable option than repair alone in the setting of a multiligament knee injury.
Assessment of Bone Quality within the Tuberosities of the Osteoporotic Humeral Head
Authors: Kirchhoff Chlodwig , Braunstein Volker , Milz Stefan , Sprecher Christoph M. , Fischer Florian , Tami Andrea , Ahrens Philipp , Imhoff Andreas B. , Hinterwimmer Stefan
Published: February 2010

Background

Tears of the rotator cuff are highly prevalent in patients older than 60 years, thereby presenting a population also suffering from osteopenia or osteoporosis. Suture fixation in the bone depends on the holding strength of the anchoring technique, whether a bone tunnel or suture anchor is selected. Because of osteopenic or osteoporotic bone changes, suture anchors in the older patient might pull out, resulting in failure of repair.

Hypothesis

The aim of our study was to analyze the bone quality within the tuberosities of the osteoporotic humeral head using high-resolution quantitative computed tomography (HR-pQCT).

Study Design

Descriptive laboratory study.

Methods

Thirty-six human cadaveric shoulders were analyzed using HR-pQCT. The mean bone volume to total volume (BV/TV) as well as trabecular bone mineral densities (trabBMDs) of the greater tuberosity (GT) and the lesser tuberosity (LT) were determined. Within the GT, 6 volumes of interest (VOIs) within the LT, and 2 VOIs and 1 control volume within the subchondral area beyond the articular surface were set.

Results

Comparing BV/TV of the medial and the lateral row, significantly higher values were found medially (P < .001). The highest BV/TV, 0.030% ± 0.027%, was found in the posteromedial portion of the GT (P < .05). Regarding the analysis of the LT, no difference was found comparing the superior (BV/TV: 0.024% ± 0.022%) and the inferior (BV/TV: 0.019% ± 0.016%) portion. Analyzing trabBMD, equal proportions were found. An inverse correlation with a correlation coefficient of —0.68 was found regarding BV/TV of the posterior portion of the GT and age (P < .05).

Conclusion

Significant regional differences of trabecular microarchitecture were found in our HR-pQCT study. The volume of highest bone quality resulted for the posteromedial aspect of the GT. Moreover, a significant correlation of bone quality within the GT and age was found, while the bone quality within the LT seems to be independent from it.

Clinical Relevance

The shape of the rotator cuff tear largely determines the bony site of tendon reattachment, although the surgeon has distinct options to modify anchor positioning. According to our results, placement of suture anchors in a medialized way at the border to the articular surface might guarantee a better structural bone stock.
Large-displacement Electrostatic Actuation of Membrane Reflectors through Mechanical Control of Electrode-membrane Gap
Authors: Korde Umesh A.
Published: February 2010

Several applications of deformable mirrors in adaptive optics and beam shaping rely on electrostatic actuation to provide the required deformation. In the case of membrane mirrors, the actuation force is frequently controlled via the potential difference across the gap between the metallized membrane and the electrode substrate. In our previous work we studied an alternative approach using a constant voltage and variable area, accomplished with appropriately centered clusters of switchable area segments. Here, we investigate controlling the force by driving the electrode substrate in a direction perpendicular to the actuator/ membrane surface. Using a single-mode non-linear model and the Lyapunov potential method, a closed-loop controller is designed for tracking a trajectory derived to meet prescribed performance criteria (such as steady deflection, bandwidth, and damping ratio). The velocity-observer input is derived from beam response measurements obtained using a quad cell beam position finder. The controller is found to be robust to a class of measurement errors affecting the quad cell output and a class of membrane velocity errors arising from platform vibrations, where both types of error are modeled as first-order Markov processes. The analytical results are confirmed using numerical simulations, showing the technique to be fairly successful at meeting the prescribed performance requirements for large deflections at moderate voltages and areas.
Adaptive Residual Useful Life Estimation of a Structural Hotspot
Authors: Mohanty Subhasish , Chattopadhyay Aditi , Peralta Pedro
Published: February 2010

In conventional approaches to life prognosis, damage tolerance and fatigue life predictions are obtained based on assumed structural flaws, regardless of whether they actually occur in service. Consequently, a large degree of conservatism is incorporated into structural designs due to these uncertainties. In a real time environment, keeping track of the damage growth in a complex structural component manually is quite difficult and requires automatic damage state estimation. The current research on structural health monitoring (or on-line damage state estimation) techniques offers condition-based damage state prediction and corresponding residual useful life assessment. The real-time damage state information from an on-line state estimation model can be regularly fed to a predictive model to update the residual useful life estimation in the event of a new prevailing situation. This article discusses the use of an adaptive prognosis procedure, which integrates an on-line state estimation algorithm with an off-line predictive algorithm to estimate the condition-based residual useful life of structural hotspots such as a lug joint.
Static Performance of Hot Bonded and Cold Bonded Inserts in Honeycomb Panels
Authors: Bianchi G. , Aglietti G.S. , Richardson G.
Published: February 2010

An investigation on the structural performance of inserts within honeycomb sandwich panels is presented. The investigation considers metallic inserts in all aluminum sandwich panels and emphasis is placed on the structural performance difference between hot bonded and cold bonded inserts. The former are introduced during panel manufacture while the latter are potted into existing panels. The investigation focuses on the static performance of the two insert systems subject to loads in the normal direction to the facing plane. The experimental part of the work presented involved carrying out pullout tests on hot bonded and cold bonded reference samples by loading them at a centrally located insert. The experimental results were compared with results from an analytical model and results from a finite element model. Contrary to what was expected it was found from the experiments that the cold bonded inserts outperformed the hot bonded inserts in terms of load carrying capability. From the finite element study it was found that this was mainly due to the difference in stiffness of the different filler materials used in the two insert systems.
Effects of water exercise swimming program on aquatic skills and social behaviors in children with autism spectrum disorders
Authors: Pan Chien-Yu
Published: February 2010

The purpose of this study was to determine the effectiveness of a 10 week water exercise swimming program (WESP) on the aquatic skills and social behaviors of 16 boys with autism spectrum disorders (ASDs). In the first 10 week phase (phase I), eight children (group A) received the WESP while eight children (group B) did not. A second 10 week phase (phase II) immediately followed, with the treatments reversed. Both groups continued their regular treatment/ activity throughout the study. Improvements were seen in aquatic skills for both groups subsequent to the WESP. Following phase I, significant social improvements were seen in group A. Following phase II, social improvements were seen for group B, whereas group A merely maintained the improvements they attained through the implementation of the WESP during phase I. Results indicate that the WESP improved aquatic skills in the participants, and holds potential for social improvements.
The atypical development of metaphor and metonymy comprehension in children with autism
Authors: Rundblad Gabriella , Annaz Dagmara
Published: February 2010

One of the most noticeable problems in autism involves the social use of language such as metaphor and metonymy, both of which are very common in daily language use. The present study is the first to investigate the development of metaphor and metonymy comprehension in autism. Eleven children with autism were compared to 17 typically developing children in a metaphor-metonymy comprehension task. Cross-sectional trajectory analyses were used to compare the development of metaphor and metonymy comprehension using a child-friendly story picture task. Trajectories were constructed linking task performance either to chronological age or to measures of mental age. Children with autism showed an impaired metaphor comprehension in relation to both chronological and mental age, whereas performance on metonymy was delayed and in line with their receptive vocabulary. Our results suggest that understanding of metaphors and metonyms are severely affected at all ages examined in the current study.
Preliminary studies on human aldosterone synthase (CYP11B2) gene polymorphism, matrix metalloprotease-9, apoptosis, and carotid atherosclerosis plaque size by proton magnetic resonance imaging
Authors: Sharma Rakesh , Katz Jose
Published: February 2010

Hypothesis. Aldosterone has direct or indirect effects on atherosclerosis, and polymorphisms occur in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalysing aldosterone biosynthesis. Genetic variations in aldosterone synthesis may influence progression of carotid atherosclerosis.

Materials and methods. Ten subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promotor) and the other in the second intron. In vivo plaque size was estimated by H-1 magnetic resonance imaging using gradient echo pulse sequence. Media-intima thickness and ex vivo plaque in endarterectomy samples were measured by histology. Matrix metalloprotease (MMP)-9 was stained in endarterectomy histology sections and apoptosis index was counted in these sections.

Results. The CYP11B2 promoter genotype patterns were associated significantly with the plaque size in carotid artery (r2=0.9987; p=0.001), MMP-9 levels (r 2=0.9878; p=0.0001) and apoptotic indices (r2=0.9495; p=0.005) by multiple regression analysis. The media-intima thickness was not significantly correlated with genotype patterns.

Conclusion. Genetic variations in aldosterone synthase (CYP11B2) gene are associated with the progression of atherosclerotic plaque size, MMP-9 and apoptosis in the carotid artery.
Water Absorbency of Jute—Polypropylene Blended Needle-punched Nonwoven
Authors: Debnath Sanjoy , Madhusoothanan M.
Published: February 2010

The effect of fabric weight, needling density, and blend proportion of jute and polypropylene fibers on water absorbency, fabric thickness, and fabric density has been studied. Box and Behnken experimental design has been used for preparation of needle-punched nonwoven fabric samples. Cluster analysis has been used to study the grouping behavior of the variables. Water absorbency increases with the increase in jute content. Water absorbency decreases with the increase in fabric weight and needling density. Highest water absorbency (720%) of the fabric can be obtained at 60% jute content level with lower needling density and lower fabric weight. The fabric thickness increases with the increase in jute content. At higher level of jute content, with the increase in needling density, the fabric thickness shows decrease in trend. At higher level of fabric weight and higher needling density, with the increase in jute content, the fabric thickness shows a decrease in trend. Maximum fabric density can be obtained at higher fabric weight (450 g/m 2), higher jute content (60%) and higher needling density (350 punches/cm 2) levels. The influence of fabric weight, needling density, and blend proportion of polypropylene and jute as independent variables on the cluster of fabric thickness and water absorbency is very high as evidence from the Euclidean distances.
Development of Natural Fiber Nonwovens for Application as Car Interiors for Noise Control
Authors: Thilagavathi G. , Pradeep E. , Kannaian T. , Sasikala L.
Published: February 2010

As natural fibers are noise-absorbing materials, renewable and biodegradable nonwovens have been developed using natural fibers such as banana, bamboo, and jute fibers for the automotive interiors to reduce noise, which currently contain traditional materials such as glass and other manufactured fibers and foams that are difficult to recycle. Three types of nonwovens were developed using needle-punching technique by blending bamboo, banana, and jute fibers with polypropylene staple fibers in the ratio of 50 : 50. Sound absorption coefficient was tested by impedance tube method (ASTM E 1050). Comparison of physical properties such as areal density, thickness, stiffness, tensile strength, elongation, structural properties, and comfort properties such as air permeability and thermal conductivity were performed for all samples. It is observed that the bamboo/polypropylene nonwoven with its compact structure showed, higher tensile strength, higher stiffness, lower elongation, lower thermal conductivity, lower air permeability, and good absorption coefficient than others and it is suitable for the automotive interior noise control. At 800 Hz, the absorption coefficient of bamboo/polypropylene and jute/ polypropylene is equivalent to the target level but it is lower by 22% in banana/ polypropylene. But at higher frequencies (1600 Hz), there is a reduction from the target level in all the nonwovens, which could be improved by increasing the thickness of the nonwovens.
Mediatization and Personalization of Politics in Italy and France: The Cases of Berlusconi and Sarkozy
Authors: Campus Donatella
Published: February 2010

In contemporary democracies, the construction of political leadership is driven by communication strategies with greater emphasis on image over substance and personality over ideology. This article analyzes two countries, Italy and France, that have been recently characterized by a remarkable increase in the personalization and mediatization of politics. First, the article intends to identify some key features of the leadership that emerge and prove to be successful in mediatized democracies. Second, the article makes a comparison of Italian and French electoral campaigns, paying special attention to the role of the media in the construction of leadership. Finally, the article examines the cases of two leaders who have left their mark on recent electoral campaigns and are credited with remarkable expertise in political marketing and news management: Silvio Berlusconi and Nicolas Sarkozy.
Climatic changes during the Pliocene as observed from climate-sensitive rocks and clay minerals of the Sedom formation, the Dead Sea Basin
Authors: Shoval S. , Zlatkin O.
Published: February 2010

The climatic history of the Dead Sea region during the Pliocene and its global connection are observed from climate-sensitive rocks and clay minerals of the Sedom formation. The Sedom formation consists of evaporative halitic rock salt units and calcareous shale units that were deposited in the Dead Sea Basin during the Pliocene. The precipitation of the rock salts took place in the hypersaline sabkha environment of the Sedom Lagoon. The extensive evaporative conditions are related to an extremely dry and warm arid climate at that time. In the arid climate, the influx of meteoric water by the drainage system of the Sedom Lagoon was limited and permitted a large concentration of lagoonal brine as well as a small rate of detritus transportation to the lagoon. Accessory sepiolite found in the rock salt appears to be neoformed from brine enriched with Mg and poor in Al under the extreme salinity condition. The small amounts of Al are in accordance with the small number of detrital minerals in the rock salts. The replacement in the deposition of the rock salt members with the calcareous shale members demonstrates a decrease in the salinity of the brine in the Sedom Basin and an increase in the deposition of detritus. The change in conditions was related to a period of deposition under a more humid climate where the erosion and the transport of detritus by the drainage system to the Sedom Basin was higher, causing the deposition of calcareous shales. Palygorskite found in the calcareous shales appears to be neoformed from brine enriched with Mg and containing Al in conditions of reduced salinity of the Sedom Basin. The larger amounts of Al are in accordance with the abundance of detrital minerals in the calcareous shales.

The depositional cycles of the Sedom formation, the cyclic fluctuation of the climatic-hydrologic conditions from an arid to a more humid climate and their correlation with sea-level fluctuations and transgression-regression cycles of the Mediterranean Sea seem to be a response to corresponding global interglacial and glacial periods during the Pliocene.
Removal of heavy metal ions from wastewaters using natural clays
Authors: Bedelean H. , Măicăneanu A. , Burcă S. , Stanca M.
Published: February 2010

A bentonite sample from the Petreş ti deposit, Cluj County (Romania), was used to remove heavy-metal ions (Cd2+, Pb2+, Cr3+) from wastewaters. A representative sample of bentonite (P) was characterized using the Brunauer-Emmett-Teller (BET) method, wet chemical analyses, X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) spectroscopy. The bentonite deposit from Petreş ti is present at the contact between Upper Jurassic limestones and basaltic andesites with subordinate basalt bodies. These rocks are composed of clay minerals (mainly smectite), with opal, quartz, feldspar and mica/illite as minor phases. The bentonite sample was used in powdered form (d< 0.2 mm) without any chemical treatment. The influence of the working regime, static and dynamic, on the process efficiency was studied using monocomponent synthetic wastewaters containing Cd, Pb and Cr ions. The bentonite sample proved to be efficient for the removal of these heavy-metal ions; removal efficiencies up to 100% (lead removal) were achieved.
Natural mixture of silica and smectite as a new clayey material for industrial applications
Authors: Sohling U. , Ruf F. , Schurz K. , Emmerich K. , Steudel A. , Schuhmann R. , Weidler P. , Ralla K. , Riechers D. , Kasper C. , Scheper T.
Published: February 2010

The main physico-chemical properties of a new smectitic clay containing large amounts of amorphous material are reviewed and potential industrial applications of this type of clay are discussed. Due to a 34% amorphous material content (natural silica gel), the investigated clay has very high porosity and can be used as it is or in acid-impregnated form for oil bleaching or phosphate reduction in edible oil. In the field of biodiesel purification, the new clay can be used to remove, in particular, mono-, diglycerides and glycerol. The natural silica-smectite mixture is also suitable as a carrier for liquid ingredients, for example in animal feeds, and might serve as a partial or complete substitute for synthetic precipitated silicas. In the field of bioseparation processes, the clay can be used as an adsorbent for protein separation by means of cation exchange. Due to the suppressed swelling (compared with smectite alone), it can be packed in columns which can be regenerated.
c-Abl mediates endothelial apoptosis induced by inhibition of integrins αvβ3 and αvβ5 and by disruption of actin
Authors: Xu Jingying , Millard Melissa , Ren Xiuhai , Cox Orla T. , Erdreich-Epstein Anat
Published: February 2010

Inhibition of integrins αvβ3 and αvβ5 in human brain microvascular endothelial cells (HBMECs) by the function-blocking peptide RGDfV induces loss of spreading on vitronectin, cell detachment, and apoptosis. We demonstrate that cell detachment is not required for apoptosis because plating on bovine serum albumin–blocked poly-L-lysine (allows attachment, but not integrin ligation and cell spreading) also induced apoptosis. Latrunculin B (LatB), which inhibits F-actin polymerization, induced transient loss of HBMEC spreading on vitronectin, but not their detachment, and induced apoptosis despite recovery of cell spreading. However, LatB did not cause apoptosis in 5 tumor cell lines. In HBMECs, both LatB and RGDfV induced transient Y412 and Y245 phosphorylation of endogenous c-Abl, a nonreceptor tyrosine kinase that reciprocally regulates F-actin. LatB also induced nuclear translocation of c-Abl in HBMECs. STI-571 (imatinib), a targeted therapy for BCR-ABL1+ leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. LatB-induced HBMEC apoptosis, and its inhibition by STI-571 also occurred in a 3-dimensional collagen model, supporting physiologic relevance. Last, siRNA to c-Abl (but not nonspecific siRNA) also inhibited RGDfV- and LatB-induced apoptosis. Thus, endogenous c-Abl mediates endothelial apoptosis induced by inhibition of integrins αvβ3/αvβ5 or by LatB-induced disruption of F-actin.
Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial
Authors: Stork Linda C. , Matloub Yousif , Broxson Emmett , La Mei , Yanofsky Rochelle , Sather Harland , Hutchinson Ray , Heerema Nyla A. , Sorrell April D. , Masterson Margaret , Bleyer Archie , Gaynon Paul S.
Published: February 2010

The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (± 1.8%) and to MP was 79.0% (± 2.1%; P = .004 log rank), although overall survival was 91.9% (± 1.4%) and 91.2% (± 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m2 per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m2 (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.
LAITOR - Literature Assistant for Identification of Terms co-Occurrences and Relationships
Authors: Barbosa-Silva Adriano , Soldatos Theodoros G , Magalhães Ivan LF , Pavlopoulos Georgios A , Fontaine Jean-Fred , Andrade-Navarro Miguel A , Schneider Reinhard , Ortega J Miguel
Published: February 2010

Background

Biological knowledge is represented in scientific literature that often describes the function of genes/proteins (bioentities) in terms of their interactions (biointeractions). Such bioentities are often related to biological concepts of interest that are specific of a determined research field. Therefore, the study of the current literature about a selected topic deposited in public databases, facilitates the generation of novel hypotheses associating a set of bioentities to a common context.

Results

We created a text mining system (LAITOR:LiteratureAssistant forIdentification ofTerms co-Occurrences andRelationships) that analyses co-occurrences of bioentities, biointeractions, and other biological terms in MEDLINE abstracts. The method accounts for the position of the co-occurring terms within sentences or abstracts. The system detected abstracts mentioning protein-protein interactions in a standard test (BioCreative II IAS test data) with a precision of 0.82-0.89 and a recall of 0.48-0.70. We illustrate the application of LAITOR to the detection of plant response genes in a dataset of 1000 abstracts relevant to the topic.

Conclusions

Text mining tools combining the extraction of interacting bioentities and biological concepts with network displays can be helpful in developing reasonable hypotheses in different scientific backgrounds.
Comparative genomics reveals selective distribution and domain organization of FYVE and PX domain proteins across eukaryotic lineages
Authors: Banerjee Sumana , Basu Soumalee , Sarkar Srimonti
Published: February 2010

Background

Phosphatidylinositol 3-phosphate is involved in regulation of several key cellular processes, mainly endocytosis, signaling, nuclear processes, cytoskeletal remodelling, cell survival, membrane trafficking, phagosome maturation and autophagy. In most cases effector proteins bind to this lipid, using either FYVE or PX domain. These two domains are distributed amongst varied life forms such as virus, protists, fungi, viridiplantae and metazoa. As the binding ligand is identical for both domains, the goal of this study was to understand if there is any selectivity for either of these domains in different taxa. Further, to understand the different cellular functions that these domains may be involved in, we analyzed the taxonomic distribution of additional domains that associate with FYVE and PX.

Results

There is selectivity for either FYVE or PX in individual genomes where both domains are present. Fungi and metazoa encode more PX, whereas streptophytes in viridiplantae encode more FYVE. Excess of FYVE in streptophytes results from proteins containing RCC1and DZC domains and FYVE domains in these proteins have a non-canonical ligand-binding site. Within a taxonomic group the selected domain associates with a higher number of other domains and is thus expected to discharge a larger number of cellular functions. Also, while certain associated domains are present in all taxonomic groups, most of them are unique to a specific group indicating that while certain common functions are discharged by these domains in all taxonomic groups, some functions appear to be group specific.

Conclusions

Although both FYVE and PX bind to PtdIns(3)P, genomes of different taxa show distinct selectivity of encoding either of the two. Higher numbers of taxonomic group specific domains co-occur with the more abundant domain (FYVE/PX) indicating that group-specific rare domain architectures might have emerged to accomplish certain group-specific functions.
The Arabidopsis pop2-1mutant reveals the involvement of GABA transaminase in salt stress tolerance
Authors: Renault Hugues , Roussel Valérie , El Amrani Abdelhak , Arzel Matthieu , Renault David , Bouchereau Alain , Deleu Carole
Published: February 2010

Background

GABA (γ-aminobutyric acid) is a non protein amino acid that has been reported to accumulate in a number of plant species when subjected to high salinity and many other environmental constraints. However, no experimental data are to date available on the molecular function of GABA and the involvement of its metabolism in salt stress tolerance in higher plants. Here, we investigated the regulation of GABA metabolism in Arabidopsis thaliana at the metabolite, enzymatic activity and gene transcription levels upon NaCl stress.

Results

We identified the GABA transaminase (GABA-T), the first step of GABA catabolism, as the most responsive to NaCl. We further performed a functional analysis of the corresponding gene POP2 and demonstrated that the previously isolated loss-of-function pop2-1 mutant was oversensitive to ionic stress but not to osmotic stress suggesting a specific role in salt tolerance. NaCl oversensitivity was not associated with overaccumulation of Na+ and Cl- but mutant showed a slight decrease in K+. To bring insights into POP2 function, a promoter-reporter gene strategy was used and showed that POP2 was mainly expressed in roots under control conditions and was induced in primary root apex and aerial parts of plants in response to NaCl. Additionally, GC-MS- and UPLC-based metabolite profiling revealed major changes in roots of pop2-1 mutant upon NaCl stress including accumulation of amino acids and decrease in carbohydrates content.

Conclusions

GABA metabolism was overall up-regulated in response to NaCl in Arabidopsis. Particularly, GABA-T was found to play a pivotal function and impairment of this step was responsible for a decrease in salt tolerance indicating that GABA catabolism was a determinant of Arabidopsis salt tolerance. GABA-T would act in salt responses in linking N and C metabolisms in roots.
Primary care Identification and Referral to Improve Safety of women experiencing domestic violence (IRIS): protocol for a pragmatic cluster randomised controlled trial
Authors: Gregory Alison , Ramsay Jean , Agnew-Davies Roxane , Baird Kathleen , Devine Angela , Dunne Danielle , Eldridge Sandra , Howell Annie , Johnson Medina , Rutterford Clare , Sharp Debbie , Feder Gene
Published: February 2010

Background

Domestic violence, which may be psychological, physical, sexual, financial or emotional, is a major public health problem due to the long-term health consequences for women who have experienced it and for their children who witness it. In populations of women attending general practice, the prevalence of physical or sexual abuse in the past year from a partner or ex-partner ranges from 6 to 23%, and lifetime prevalence from 21 to 55%. Domestic violence is particularly important in general practice because women have many contacts with primary care clinicians and because women experiencing abuse identify doctors and nurses as professionals from whom they would like to get support. Yet health professionals rarely ask about domestic violence and have little or no training in how to respond to disclosure of abuse.

Methods/Design

This protocol describes IRIS, a pragmatic cluster randomised controlled trial with the general practice as unit of randomisation. Our trial tests the effectiveness and cost-effectiveness of a training and support programme targeted at general practice teams. The primary outcome is referral of women to specialist domestic violence agencies. Forty-eight practices in two UK cities (Bristol and London) are randomly allocated, using minimisation, into intervention and control groups. The intervention, based on an adult learning model in an educational outreach framework, has been designed to address barriers to asking women about domestic violence and to encourage appropriate responses to disclosure and referral to specialist domestic violence agencies. Multidisciplinary training sessions are held with clinicians and administrative staff in each of the intervention practices, with periodic feedback of identification and referral data to practice teams. Intervention practices have a prompt to ask about abuse integrated in the electronic medical record system. Other components of the intervention include an IRIS champion in each practice and a direct referral pathway to a named domestic violence advocate.

Discussion

This is the first European randomised controlled trial of an intervention to improve the health care response to domestic violence. The findings will have the potential to inform training and service provision.

Trial registration

ISRCTN74012786
Effect of cardiometabolic risk factors on hypertension management: a cross-sectional study among 28 physician practices in the United States
Authors: Belletti Daniel A , Zacker Christopher , Wogen Jenifer
Published: February 2010

Objective

This cross-sectional study sought to determine the prevalence of cardiometabolic risk factor clusters (CMRFCs) and their effect on BP control among hypertensive patients from 28 US physician practices.

Methods

Each participating practice identified a random sample of 150-300 adults aged ≥ 18 years diagnosed with hypertension. The primary outcome variable was BP control (BP < 140/90 mmHg for non-diabetic and <130/80 mmHg for diabetic patients). CMRFCs included hypertension in addition to obesity, dyslipidemia, and diabetes.

Results

Overall, 6,527 hypertensive patients were identified for study inclusion. More than half (54.3%) were female, and mean age was 64.7 years. Almost half (48.7%) were obese (BMI ≥ 30 kg/m2). About 1 in every 4 patients (25.3%) had diabetes, and 60.7% had dyslipidemia. Mean blood pressure was 132.5/77.9 mmHg, and 55.0% of all patients had controlled BP; 62.4% of non-diabetic patients, and 33.3% of diabetic hypertensive patients, had BP controlled to recommended levels. Most (81.7%) hypertensive patients had ≥ 1 cardiometabolic risk factor, and 12.2% had all 3 risk factors. As compared to hypertensive patients without additional risk factors, adjusted odds ratios for BP control were significantly lower for all combinations of CMRFCs (ORs 0.15-0.83, all p < 0.04), with the exception of patients who had only dyslipidemia in addition to hypertension (OR = 1.09, p = NS). Prescriber adherence to recommended hypertension treatment guidelines for patients with diabetes, heart failure, or prior myocardial infarction was high. Although patients with risk factors were prescribed more antihypertensive medications than those without, hypertensive patients with all 3 risk factors were prescribed a mean of 2.4 antihypertensive medications compared to 1.7 for those with no risk factors; odds of BP control in these patients, however, was 0.23 [95% CI 0.19-0.29] that of patients with no other CMRFCs.

Conclusions

Across 28 US practices, only 18% of hypertensive patients did not have any additional cardiometabolic risk factors. The high prevalence of CMRFCs presents a challenge to effective hypertension management.
Geographical patterns and predictors of malaria risk in Zambia: Bayesian geostatistical modelling of the 2006 Zambia national malaria indicator survey (ZMIS)
Authors: Riedel Nadine , Vounatsou Penelope , Miller John M , Gosoniu Laura , Chizema-Kawesha Elizabeth , Mukonka Victor , Steketee Rick W
Published: February 2010

Background

The Zambia Malaria Indicator Survey (ZMIS) of 2006 was the first nation-wide malaria survey, which combined parasitological data with other malaria indicators such as net use, indoor residual spraying and household related aspects. The survey was carried out by the Zambian Ministry of Health and partners with the objective of estimating the coverage of interventions and malaria related burden in children less than five years. In this study, the ZMIS data were analysed in order (i) to estimate an empirical high-resolution parasitological risk map in the country and (ii) to assess the relation between malaria interventions and parasitaemia risk after adjusting for environmental and socio-economic confounders.

Methods

The parasitological risk was predicted from Bayesian geostatistical and spatially independent models relating parasitaemia risk and environmental/climatic predictors of malaria. A number of models were fitted to capture the (potential) non-linearity in the malaria-environment relation and to identify the elapsing time between environmental effects and parasitaemia risk. These models included covariates (a) in categorical scales and (b) in penalized and basis splines terms. Different model validation methods were used to identify the best fitting model. Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting model.

Results

Model validation indicated that linear environmental predictors were able to fit the data as well as or even better than more complex non-linear terms and that the data do not support spatial dependence. Overall the averaged population-adjusted parasitaemia risk was 20.0% in children less than five years with the highest risk predicted in the northern (38.3%) province. The odds of parasitaemia in children living in a household with at least one bed net decreases by 40% (CI: 12%, 61%) compared to those without bed nets.

Conclusions

The map of parasitaemia risk together with the prediction error and the population at risk give an important overview of the malaria situation in Zambia. These maps can assist to achieve better resource allocation, health management and to target additional interventions to reduce the burden of malaria in Zambia significantly. Repeated surveys will enable the evaluation of the effectiveness of on-going interventions.
Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells
Authors: Shi Mei , Wang Hong-Na , Xie Shu-Tao , Luo Yan , Sun Cai-Yun , Chen Xiu-Lan , Zhang Yu-Zhong
Published: February 2010

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world which is highly chemoresistant to currently available chemotherapeutic agents. Thus, novel therapeutic targets are needed to be sought for the successful treatment of HCC. Peptaibols, a family of peptides synthesized non-ribosomally by the Trichoderma species and other fungi, exhibit antibiotic activities against bacteria and fungi. Few studies recently showed that peptaibols exerted cytotoxicity toward human lung epithelial and breast carcinoma cells. However, the mechanism involved in peptaibol-induced cell death remains poorly understood.

Results

Here, we showed that Trichokonin VI (TK VI), a peptaibol from Trichoderma pseudokoningii SMF2, induced growth inhibition of HCC cells in a dose-dependent manner. It did not obviously impair the viability of normal liver cells at lower concentration. Moreover, the suppression of cell viability resulted from the programmed cell death (PCD) with characteristics of apoptosis and autophagy. An influx of Ca2+ triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and subsequent promotion of apoptosis. On the other hand, typically morphological characteristics consistent with autophagy were also observed by punctate distribution of MDC staining and the induction of LC3-II, including extensive autophagic vacuolization and enclosure of cell organelles by these autophagosomes. More significantly, specific depletion of Bak expression by small RNA interfering (siRNA) could partly attenuate TK VI-induced autophagy. However, siRNA against Bax led to increased autophagy.

Conclusion

Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells.
Synergistic effect of gefitinib and rofecoxib in mesothelioma cells
Authors: Stoppoloni Daniela , Canino Claudia , Cardillo Irene , Verdina Alessandra , Baldi Alfonso , Sacchi Ada , Galati Rossella
Published: February 2010

Background

Malignant mesothelioma (MM) is an aggressive tumor that is resistant to conventional modes of treatment with chemotherapy, surgery or radiation. Research into the molecular pathways involved in the development of MM should yield information that will guide therapeutic decisions. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are involved in the carcinogenesis of MM. Combination of COX-2 and EGFR inhibitors, therefore, could be an effective strategy for reducing cell growth in those lines expressing the two molecular markers.

Results

In order to verify the effect of COX-2 and EGFR inhibitors, five MM cell lines NCI-2452, MPP89, Ist-Mes-1, Ist-Mes-2 and MSTO-211 were characterized for COX-2 and EGFR and then treated with respective inhibitors (rofecoxib and gefitinib) alone and in combination. Only MPP89, Ist-Mes-1 and Ist-Mes-2 were sensitive to rofecoxib and showed growth-inhibition upon gefitinib treatment. The combination of two drugs demonstrated synergistic effects on cell killing only in Ist-Mes-2, the cell line that was more sensitive to gefitinib and rofecoxib alone. Down-regulation of COX-2, EGFR, p-EGFR and up-regulation of p21 and p27 were found in Ist-Mes-2, after treatment with single agents and in combination. In contrast, association of two drugs resulted in antagonistic effect in Ist-Mes-1 and MPP89. In these cell lines after rofecoxib exposition, only an evident reduction of p-AKT was observed. No change in p-AKT in Ist-Mes-1 and MPP89 was observed after treatment with gefitinib alone and in combination with rofecoxib.

Conclusions

Gefitinib and rofecoxib exert cell type-specific effects that vary between different MM cells. Total EGFR expression and downstream signalling does not correlate with gefitinib sensitivity. These data suggest that the effect of gefitinib can be potentiated by rofecoxib in MM cell lines where AKT is not activated.
Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family
Authors: Kong Weimin , Yen Jui-Hung , Vassiliou Evros , Adhikary Sabina , Toscano Miguel G , Ganea Doina
Published: February 2010

Background

Acute and chronic inflammation play essential roles in inflammatory/autoimmune conditions. Protective anti-inflammatory effects of the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were reported in animal models of colitis, sepsis, and stroke. Since dendritic cells (DC) represent the essential cellular link between innate and adaptive immunity and have a prominent role in tolerance for self-antigens, we sought to investigate the impact of DHA on DC maturation and proinflammatory cytokine production.

Methods

Murine bone marrow-derived DC were treated with DHA and stimulated with various toll-like receptor (TLR) ligands. Flow cytometry was used to determine the levels of surface maturation markers and endocytic activity. Cytokine expression and secretion were measured by real-time RT-PCR and ELISA assays. PPARγ and NFκB activity in nuclear extracts were determined by binding to specific oligonucleotide sequences using ELISA-based assays. In vivo effects of DHA were assessed in splenic DC from LPS-inoculated mice maintained on a DHA-enriched diet.

Results

DHA maintained the immature phenotype in bone marrow-derived DC by preventing the upregulation of MHCII and costimulatory molecules (CD40, CD80 and CD86) and maintaining high levels of endocytic activity. DHA inhibited the production of pro-inflammatory cytokines, including the IL-12 cytokine family (IL-12p70, IL-23, and IL-27), from DC stimulated with TLR2, 3, 4, and 9 ligands. DHA inhibition of IL-12 expression was mediated through activation of PPARγ and inhibition of NFκBp65 nuclear translocation. DHA exerted a similar inhibitory effect on IL-12 and IL-23 expression in vivo in LPS-inoculated mice maintained on a DHA-enriched diet.

Conclusions

Exposure of bone marrow-derived DC to DHA resulted in the maintenance of an immature phenotype and drastic reduction in proinflammatory cytokine release. DHA inhibited the expression and secretion of the IL-12 cytokine family members (IL-12p70, IL-23 and IL-27), which play essential roles in the differentiation of the proinflammatory Th1/Th17 effector cells. The effect of DHA on IL-12 expression was mediated through activation of PPARγ and inhibition of NFκB. Inhibition of IL-12 and IL-23 expression was also evident in splenic DC from mice fed a DHA-enriched diet, suggesting that dietary DHA acts as an anti-inflammatory agent in vivo.