bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical analysis of composite-film hydrodynamic bearings
Authors: Szeri Andras
Published: November 2012

Major aspects that influence quality and efficiency of the hydrodynamic lubrication of tribological contacts are the surface properties of the contact, the properties of the lubricant, and the structure of the lubricant film. In search for efficiency, past approaches focused on surface modification techniques (surface texturing) and modification of lubricant properties (lubricant additives). The idea in this article is to modify the structure of the lubricant film itself. In contrast to a traditional bearing, the composite-film bearing advocated here relies on a double-layer, composite, lubricant film for separating the load-bearing surfaces. (One of the Reviewers pointed out that ‘the functions of friction modifiers and antiwear additives are to form a boundary lubrication layer, which has a higher apparent viscosity than the bulk lubrication oil, and resulting in a sandwich structure of lubrication film. In this sense, the composite film lubrication has been used in many practical tribosystems already’.)

 Our first version of the composite-film bearing was based on an observation that to minimize frictional losses, two immiscible liquids of distinct viscosities will arrange into (stable) configurations that separates the component liquids while concentrating shear deformation in the low viscosity component. However, particularly in turbulent flow of the lubricant, reliance on the above principle might not be adequate, and, in this article, we offer a new composite-film bearing construct in which actual physical boundary separates the two component films. For journal bearings, this naturally leads to the concept of the ‘floating-ring’ bearing, with two distinctly different lubricants occupying the inside and the outside clearance spaces. We show here that the new version of the composite-film bearing, i.e. a floating-ring bearing lubricated with two distinctly different liquids, performs not unlike its first kind; specifically, its application leads to substantial reduction of viscous losses, over 90% in some cases, while maintaining safe film dimensions.
Practical challenges in determining piston ring friction
Authors: Liao Kai , Liu Yang , Kim Dallwoo , Urzua Paulo , Tian Tian
Published: November 2012

Practical challenges from both experiment and calculation sides were discussed for determining two piece twin land oil control ring friction. A floating liner engine was used for twin land oil control ring study. Effects of floating liner engine system dynamics and piston skirt friction were addressed and methods to mitigate them were discussed. A deterministic twin land oil control ring model was used for ring friction calculation. Variation of the surface roughness at different spots of the liner and its effects on both hydrodynamic and boundary lubrication predictions were discussed. A multi-point correlation method was introduced to address surface variation effects on the twin land oil control ring model. Ring land width variation between two lands as well as along the circumference and its effects on calculation were shown, and methods to address it were discussed. By taking all these necessary steps in both experiments and calculations, this study shows that a reasonable match can be achieved between the measured and calculated friction, which covers all three lubrication regimes. This study lays a foundation for realistically predicting the friction of piston rings in internal combustion engines.
Diagnosis and management of abdominal vascular injuries
Authors: Webb Travis P
Published: November 2012

Intra-abdominal vascular trauma is an injury that continues to challenge the general surgeon and leads to high morbidity and mortality even at busy urban trauma centers. The majority of patients arrive in hemorrhagic shock; therefore, rapid evaluation, resuscitation, and transfer to the operating room are necessary to treat these patients. In the operating room, the surgeon must have a well-planned surgical approach to the variety of potential injuries encountered in the retroperitoneal space. This article reviews the incidence, diagnostic strategies, treatment principles, and expected outcomes when dealing with intra-abdominal vascular injury.
Transplanting the adolescent cystic fibrosis patient: can we do it?
Authors: Oshrine Kathleen , McGrath Debby , Goldfarb Samuel
Published: November 2012

Bilateral lung transplantation remains a treatment for end-stage cystic fibrosis (CF) lung disease when there is no further medical or surgical treatment available. The aim of lung transplantation is to improve patient life expectancy. The consensus view that lung transplantation extends life in children has been challenged. However, challengers have faced alternative explanations of their finding and it is largely accepted that lung transplantation in the adolescent patient population is an important treatment modality. The goal of this article is to address these concerns and assist with developing creative approaches to this known challenging subset of patients. The main focus of this article will be to discuss the looming question: what existing evidence or best practice insights could improve bilateral lung transplantation outcomes for adolescent patients with end-stage CF?
Nebulized arformoterol: what is its place in the management of COPD?
Authors: Miles Matthew C. , Donohue James F. , Ohar Jill A.
Published: November 2012

Chronic obstructive pulmonary disease (COPD) is a serious global health burden. Comprehensive management of COPD includes both pharmacologic and non-pharmacologic interventions aimed at improving disease-related functional capacity, health-related quality of life, and survival. The primary medications used for treatment of COPD are inhaled bronchodilator drugs which are delivered directly to the patient’s airways through a number of different mechanisms. Arformoterol, the (R,R) enantiomer of racemic formoterol, was the first long-acting beta agonist approved by the U.S. Food and Drug Administration (FDA) for nebulized delivery. We discuss the pharmacology, clinical efficacy, and safety of arformoterol, and provide recommendations for its use during longitudinal management of patients with COPD.
Adapting an Evidence-Based HIV Intervention for At-Risk African American College Women at Historically Black Colleges and Universities Who Use Alcohol and Drugs
Authors: Sawyer-Kurian Kyla Marie , Wechsberg Wendee M.
Published: November 2012

The convergence of the high prevalence of HIV incidence among African American adolescent and adult women along with substance use and risky sexual behavior among university students necessitates the development of a HIV intervention specifically addressing culture, gender, and college factors for female African American university students. The woman-focused HIV intervention was chosen for adaptation because it has been shown to be efficacious with reducing risk for African American women who use alcohol and drugs, and has been successfully adapted 7 times. The target population was African American college women enrolled at a historically Black university who use alcohol and other drugs, and who engaged in risky sex behaviors. To understand and assess the needs of this population, we conducted four focus groups with African American college women, two in-depth interviews with faculty, and a combination of in-depth interviews and focus groups with student affairs and health staff that were analyzed using content analysis. From this analysis, several themes emerged that were used to adapt the intervention. Emerging themes included challenges related to identity and societal stereotypes, lack of knowledge about sexual health (i.e., negotiating safer sex) and the function of female and male anatomies, high incidents of pregnancy, negative consequences related to alcohol and marijuana use, and the need to incorporate testimonies from college students, media enhancements, and role-plays to convey intervention messages. After the preliminary adaptation, 11 college women reviewed the adapted intervention and provided positive feedback. Plans for future research are discussed.
Emotional Valence
Authors: Briesemeister Benny B. , Kuchinke Lars , Jacobs Arthur M.
Published: November 2012

In contrast to standard models of emotional valence, which assume a bipolar valence dimension ranging from negative to positive valence with a neutral midpoint, the evaluative space model (ESM) proposes two independent positivity and negativity dimensions. Previous imaging studies suggest higher predictive power of the ESM when investigating the neural correlates of verbal stimuli. The present study investigates further assumptions on the behavioral level. A rating experiment on more than 600 German words revealed 48 emotionally ambivalent stimuli (i.e., stimuli with high scores on both ESM dimensions), which were contrasted with neutral stimuli in two subsequent lexical decision experiments. Facilitative processing for emotionally ambivalent words was found in Experiment 2. In addition, controlling for emotional arousal and semantic ambiguity in the stimulus set, Experiment 3 still revealed a speed-accuracy trade-off for emotionally ambivalent words. Implications for future investigations of lexical processing and for the ESM are discussed.
Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up-regulation after vessel injury in mice
Authors: Robins Richard S. , Lemarié Catherine A. , Laurance Sandrine , Aghourian Meghedi N. , Wu Jianqiu , Blostein Mark D.
Published: November 2012

Gas6 (growth-arrest specific gene 6) plays a role in thrombus stabilization. Gas6 null (−/−) mice are protected from lethal venous and arterial thromboembolism through platelet signaling defects induced only by 5μM ADP and 10μM of the thromboxane analog, U46619. This subtle platelet defect, despite a dramatic clinical phenotype, raises the possibility that Gas6 from a source other than platelets contributes to thrombus formation. Thus, we hypothesize that Gas6 derived from the vascular wall plays a role in venous thrombus formation. Bone marrow transplantation and platelet depletion/reconstitution experiments generating mice with selective ablations of Gas6 from either the hematopoietic or nonhematopoietic compartments demonstrate an approximately equal contribution by Gas6 from both compartments to thrombus formation. Tissue factor expression was significantly reduced in the vascular wall of Gas6−/− mice compared with WT. In vitro, thrombin-induced tissue factor expression was reduced in Gas6−/− endothelial cells compared with wild-type endothelium. Taken together, these results demonstrate that vascular Gas6 contributes to thrombus formation in vivo and can be explained by the ability of Gas6 to promote tissue factor expression and activity. These findings support the notion that vascular wall-derived Gas6 may play a pathophysiologic role in venous thromboembolism.
Plasmid DNA immunization with Trypanosoma cruzi genes induces cardiac and clinical protection against Chagas disease in the canine model
Authors: Rodríguez-Morales Olivia , Pérez-Leyva M Magdalena , Ballinas-Verdugo Martha A , Carrillo-Sánchez Silvia C , Rosales-Encina J Luis , Alejandre-Aguilar Ricardo , Reyes Pedro A , Arce-Fonseca Minerva
Published: November 2012

The only existing preventive measure against American trypanosomosis, or Chagas disease, is the control of the transmitting insect, which has only been effective in a few South American regions. Currently, there is no vaccine available to prevent this disease. Here, we present the clinical and cardiac levels of protection induced by expression toTrypanosoma cruzigenes encoding theTcSP andTcSSP4 proteins in the canine model. Physical examination, diagnostic chagasic serology, and serial electrocardiograms were performed before and after immunization, as well as after experimental infection. We found that immunization with recombinant plasmids prevented hyperthermia in the acute phase of experimental infection and produced lymphadenomegaly as an immunological response against the parasite and additionally prevented heart rate elevation (tachycardia) in the acute and/or chronic stages of infection. Immunization withT. cruzigenes encoding theTcSP andTcSSP4 antigens diminished the quality and quantity of the electrocardiographic abnormalities, thereby avoiding progression to more severe developments such as right bundle branch block or ventricular premature complexes in a greater number of dogs.
An investigation of the resolution of inflammation (catabasis) in COPD
Authors: Noguera Aina , Gomez Cristina , Faner Rosa , Cosio Borja , González-Périz Ana , Clària Joan , Carvajal Angel , Agustí Alvar
Published: November 2012

Background

Chronic Obstructive Pulmonary Disease (COPD) is characterized by an enhanced inflammatory response to smoking that persists despite quitting. The resolution of inflammation (catabasis) is a complex and highly regulated process where tissue resident macrophages play a key role since they phagocytose apoptotic cells (efferocytosis), preventing their secondary necrosis and the spill-over of their pro-inflammatory cytoplasmic content, and release pro-resolution and tissue repair molecules, such as TGFβ, VEGF and HGF. Because inflammation does not resolve in COPD, we hypothesized that catabasis may be abnormal in these patients.

Methods

To explore this hypothesis, we studied lung tissue samples obtained at surgery from 21 COPD patients, 22 smokers with normal spirometry and 13 non-smokers controls. In these samples we used: (1) immunohistochemistry to assess the expression of CD44, CD36, VEGF and TGFβ in lung macrophages; (2) real time PCR to determine HGF, PPARγ, TGFβ, VEGF and MMP-9 gene expression; and, (3) ELISA to quantify lipoxin A4, a lipid mediator of catabasis.

Results

We found that current and former smokers with COPD showed: (1) more inflammation (higher MMP-9 expression); (2) reduced macrophage surface expression of CD44, a key efferocytosis receptor; and, (3) similar levels of TGFβ, VEGF, HGF, PPARγ, and lipoxin A4 than smokers with normal spirometry, despite the presence of inflammation and disease.

Conclusions

These results identify several potential abnormalities of catabasis in patients with COPD.
Nucleolin mediates the antiangiogenesis effect of the pseudopeptide N6L
Authors: Birmpas Charalampos , Briand Jean Paul , Courty Josẻ , Katsoris Panagiotis
Published: November 2012

Background

Nucleolin is a protein over-expressed on the surface of activated cells. Recent studies have underlined the involvement of cell surface nucleolin in angiogenesis processes. This cell surface molecule serves as a receptor for various ligands implicated in pathophysiological processes such as growth factors, cell adhesion molecules like integrins, selectins or laminin-1, lipoproteins and viruses. N6L is a synthetic multimeric pseudopeptide that binds cell surface expressed nucleolin and inhibits cell proliferation.

Results

In the present work, we further investigated the mechanisms of action of pseudopeptide N6L on angiogenesis using HUVECs. We provide evidence that N6L inhibits the in vitro adhesion, proliferation and migration of HUVECs without inducing their apoptosis. In addition, we found that N6L downregulates MMP-2 in HUVECs. The above biological actions are regulated by SRC, ERK1/2, AKT and FAK kinases as we found that N6L inhibits their activation in HUVECs. Finally, down regulation of nucleolin using siRNA demonstrated the implication of nucleolin in the biological actions of these peptides.

Conclusions

Taken together, these results indicate that N6L could constitute an interesting therapeutic tool for treating diseases associated with excessive angiogenesis.
Anopheles salivary gland proteomes from major malaria vectors
Authors: Fontaine Albin , Fusaï Thierry , Briolant Sébastien , Buffet Sylvain , Villard Claude , Baudelet Emilie , Pophillat Mathieu , Granjeaud Samuel , Rogier Christophe , Almeras Lionel
Published: November 2012

Background

Antibody responses against Anopheles salivary proteins can indicate individual exposure to bites of malaria vectors. The extent to which these salivary proteins are species-specific is not entirely resolved. Thus, a better knowledge of the diversity among salivary protein repertoires from various malaria vector species is necessary to select relevant genus-, subgenus- and/or species-specific salivary antigens. Such antigens could be used for quantitative (mosquito density) and qualitative (mosquito species) immunological evaluation of malaria vectors/host contact. In this study, salivary gland protein repertoires (sialomes) from several Anopheles species were compared using in silico analysis and proteomics. The antigenic diversity of salivary gland proteins among different Anopheles species was also examined.

Results

In silico analysis of secreted salivary gland protein sequences retrieved from an NCBInr database of six Anopheles species belonging to the Cellia subgenus (An. gambiae, An. arabiensis, An. stephensi and An. funestus) and Nyssorhynchus subgenus (An. albimanus and An. darlingi) displayed a higher degree of similarity compared to salivary proteins from closely related Anopheles species. Additionally, computational hierarchical clustering allowed identification of genus-, subgenus- and species-specific salivary proteins. Proteomic and immunoblot analyses performed on salivary gland extracts from four Anopheles species (An. gambiae, An. arabiensis, An. stephensi and An. albimanus) indicated that heterogeneity of the salivary proteome and antigenic proteins was lower among closely related anopheline species and increased with phylogenetic distance.

Conclusion

This is the first report on the diversity of the salivary protein repertoire among species from the Anopheles genus at the protein level. This work demonstrates that a molecular diversity is exhibited among salivary proteins from closely related species despite their common pharmacological activities. The involvement of these proteins as antigenic candidates for genus-, subgenus- or species-specific immunological evaluation of individual exposure to Anopheles bites is discussed.
The Schistosoma mansoni phylome: using evolutionary genomics to gain insight into a parasite’s biology
Authors: Silva Larissa Lopes , Marcet-Houben Marina , Nahum Laila Alves , Zerlotini Adhemar , Gabaldón Toni , Oliveira Guilherme
Published: November 2012

Background

Schistosoma mansoni is one of the causative agents of schistosomiasis, a neglected tropical disease that affects about 237 million people worldwide. Despite recent efforts, we still lack a general understanding of the relevant host-parasite interactions, and the possible treatments are limited by the emergence of resistant strains and the absence of a vaccine. The S. mansoni genome was completely sequenced and still under continuous annotation. Nevertheless, more than 45% of the encoded proteins remain without experimental characterization or even functional prediction. To improve our knowledge regarding the biology of this parasite, we conducted a proteome-wide evolutionary analysis to provide a broad view of the S. mansoni’s proteome evolution and to improve its functional annotation.

Results

Using a phylogenomic approach, we reconstructed the S. mansoni phylome, which comprises the evolutionary histories of all parasite proteins and their homologs across 12 other organisms. The analysis of a total of 7,964 phylogenies allowed a deeper understanding of genomic complexity and evolutionary adaptations to a parasitic lifestyle. In particular, the identification of lineage-specific gene duplications pointed to the diversification of several protein families that are relevant for host-parasite interaction, including proteases, tetraspanins, fucosyltransferases, venom allergen-like proteins, and tegumental-allergen-like proteins. In addition to the evolutionary knowledge, the phylome data enabled us to automatically re-annotate 3,451 proteins through a phylogenetic-based approach rather than solely sequence similarity searches. To allow further exploitation of this valuable data, all information has been made available at PhylomeDB (http://www.phylomedb.org).

Conclusions

In this study, we used an evolutionary approach to assess S. mansoni parasite biology, improve genome/proteome functional annotation, and provide insights into host-parasite interactions. Taking advantage of a proteome-wide perspective rather than focusing on individual proteins, we identified that this parasite has experienced specific gene duplication events, particularly affecting genes that are potentially related to the parasitic lifestyle. These innovations may be related to the mechanisms that protect S. mansoni against host immune responses being important adaptations for the parasite survival in a potentially hostile environment. Continuing this work, a comparative analysis involving genomic, transcriptomic, and proteomic data from other helminth parasites, other parasites, and vectors will supply more information regarding parasite’s biology as well as host-parasite interactions.
Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype
Authors: Motomura Takashi , Shirabe Ken , Furusyo Norihiro , Yoshizumi Tomoharu , Ikegami Toru , Soejima Yuji , Akahoshi Tomohiko , Tomikawa Morimasa , Fukuhara Takasuke , Hayashi Jun , Maehara Yoshihiko
Published: November 2012

Background

IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.

Methods

Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.

Results

Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.

Conclusions

IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.
Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCLpolymorphisms in Mexican population: a case–control study
Authors: Morales-García Guadalupe , Falfán-Valencia Ramcés , García-Ramírez Román Alejandro , Camarena Ángel , Ramirez-Venegas Alejandra , Castillejos-López Manuel , Pérez-Rodríguez Martha , González-Bonilla César , Grajales-Muñíz Concepción , Borja-Aburto Víctor , Mejía-Aranguré Juan Manuel
Published: November 2012

Background

Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009.

Methods

Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases.

Results

Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg.

Conclusion

The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus.
A descriptive study of reportable gastrointestinal illnesses in Ontario, Canada, from 2007 to 2009
Authors: Vrbova Linda , Johnson Karen , Whitfield Yvonne , Middleton Dean
Published: November 2012

Background

Gastrointestinal illnesses (GI) continue to pose a substantial burden in terms of morbidity and economic impact in Canada. We describe the epidemiology of reportable GI in Ontario by characterizing the incidence of each reportable GI, as well as associated demographics, clinical outcomes, seasonality, risk settings, and likely sources of infection.

Methods

Reports on laboratory confirmed cases of amebiasis, botulism, campylobacteriosis, cryptosporidiosis, cyclosporiasis, giardiasis, hepatitis A, listeriosis, paratyphoid fever, salmonellosis, shigellosis, typhoid fever, illness due to verotoxin-producing Escherichia coli (VTEC-illness), and yersiniosis, from January 1, 2007 to December 31, 2009 were obtained from Ontario’s passive reportable disease surveillance system. Cases were classified by history of relevant travel, association with outbreaks, and likely source of infection, obtained through follow-up of reported cases by local health authorities.

Results

There were 29,897 GI reported by health authorities in Ontario from 2007 to 2009. The most frequently reported diseases were campylobacteriosis (10,916 cases or 36.5% of all GI illnesses) and salmonellosis (7,514 cases, 25.1%). Overall, 26.9% of GI cases reported travel outside of Ontario during the relevant incubation period. Children four years of age and younger had the highest incidence rate for most GI, and significantly more (54.8%, p<0.001) cases occurred among males than females. The most commonly reported sources of infections were food (54.2%), animals (19.8%), and contact with ill persons (16.9%). Private homes (45.5%) and food premises (29.7%) were the most commonly reported exposure settings. Domestic cases of campylobacteriosis, cryptosporidiosis, giardiasis, salmonellosis, and VTEC-illness showed seasonal patterns with incidence peaking in the summer months.

Conclusions

Reportable GI continues to be a burden in Ontario. Since more than one in four GI cases experienced in Ontario were acquired outside of the province, international travel is an important risk factor for most GI. Because private homes are the most commonly reported risk settings and the main suspect sources of infection are food, animal contact and ill persons, these findings support the continued need for public health food safety programs, public education on safe handling of food and animals, and proper hand hygiene practices.
Singing classes for chronic obstructive pulmonary disease: a randomized controlled trial
Authors: Lord Victoria M , Hume Victoria J , Kelly Julia L , Cave Phoene , Silver Judith , Waldman Maya , White Chris , Smith Cayley , Tanner Rebecca , Sanchez Melissa , Man William D-C , Polkey Michael I , Hopkinson Nicholas S
Published: November 2012

Background

There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD). It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation.

Methods

Patients were randomised to either singing classes or a film club for eight weeks. Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist.

Results

The singing group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline. There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity. In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group.

Conclusion

Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity.

Trials registration

Registration Current Controlled Trials - ISRCTN17544114
Targeted DNA excision in Arabidopsis by a re-engineered homing endonuclease
Authors: Antunes Mauricio S , Smith J Jeff , Jantz Derek , Medford June I
Published: November 2012

Background

A systematic method for plant genome manipulation is a major aim of plant biotechnology. One approach to achieving this involves producing a double-strand DNA break at a genomic target site followed by the introduction or removal of DNA sequences by cellular DNA repair. Hence, a site-specific endonuclease capable of targeting double-strand breaks to unique locations in the plant genome is needed.

Results

We engineered and tested a synthetic homing endonuclease, PB1, derived from the I-CreI endonuclease ofChlamydomonas reinhardtii, which was re-designed to recognize and cleave a newly specified DNA sequence. We demonstrate that an activity-optimized version of the PB1 endonuclease, under the control of a heat-inducible promoter, is capable of targeting DNA breaks to an introduced PB1 recognition site in the genome ofArabidopsis thaliana.We further demonstrate that this engineered endonuclease can very efficiently excise unwanted transgenic DNA, such as an herbicide resistance marker, from the genome when the marker gene is flanked by PB1 recognition sites. Interestingly, under certain conditions the repair of the DNA junctions resulted in a conservative pairing of recognition half sites to remove the intervening DNA and reconstitute a single functional recognition site.

Conclusion

These results establish parameters needed to use engineered homing endonucleases for the modification of endogenous loci in plant genomes.
Structural and molecular basis of interaction of HCV non-structural protein 5A with human casein kinase 1α and PKR
Authors: Sudha Govindarajan , Yamunadevi Subburaj , Tyagi Nidhi , Das Saumitra , Srinivasan Narayanaswamy
Published: November 2012

Background

Interaction of non-structural protein 5A (NS5A) of Hepatitis C virus (HCV) with human kinases namely, casein kinase 1α (ck1α) and protein kinase R (PKR) have different functional implications such as regulation of viral replication and evasion of interferon induced immune response respectively. Understanding the structural and molecular basis of interactions of the viral protein with two different human kinases can be useful in developing strategies for treatment against HCV.

Results

Serine 232 of NS5A is known to be phosphorylated by human ck1α. A structural model of NS5A peptide containing phosphoacceptor residue Serine 232 bound to ck1α has been generated using the known 3-D structures of kinase-peptide complexes. The substrate interacting residues in ck1α has been identified from the model and these are found to be conserved well in the ck1 family. ck1α – substrate peptide complex has also been used to understand the structural basis of association between ck1α and its other viral stress induced substrate, tumour suppressor p53 transactivation domain which has a crystal structure available.

Interaction of NS5A with another human kinase PKR is primarily genotype specific. NS5A from genotype 1b has been shown to interact and inhibit PKR whereas NS5A from genotype 2a/3a are unable to bind and inhibit PKR efficiently. This is one of the main reasons for the varied response to interferon therapy in HCV patients across different genotypes. Using PKR crystal structure, sequence alignment and evolutionary trace analysis some of the critical residues responsible for the interaction of NS5A 1b with PKR have been identified.

Conclusions

The substrate interacting residues in ck1α have been identified using the structural model of kinase - substrate peptide. The PKR interacting NS5A 1b residues have also been predicted using PKR crystal structure, NS5A sequence analysis along with known experimental results. Functional significance and nature of interaction of interferon sensitivity determining region and variable region 3 of NS5A in different genotypes with PKR which was experimentally shown are also supported by the findings of evolutionary trace analysis. Designing inhibitors to prevent this interaction could enable the HCV genotype 1 infected patients respond well to interferon therapy.
Studies of the in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities of selected Thai medicinal plants
Authors: Kaewpiboon Chutima , Lirdprapamongkol Kriengsak , Srisomsap Chantragan , Winayanuwattikun Pakorn , Yongvanich Tikamporn , Puwaprisirisan Preecha , Svasti Jisnuson , Assavalapsakul Wanchai
Published: November 2012

Background

Traditional folk medicinal plants have recently become popular and are widely used for primary health care. Since Thailand has a great diversity of indigenous (medicinal) plant species, this research investigated 52 traditionally used species of Thai medicinal plants for their in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities.

Methods

The 55 dried samples, derived from the medicinally used parts of the 52 plant species were sequentially extracted by hexane, dichloromethane, ethanol and water. These 220 extracts were then screened for in vitro (i) cytotoxicity against four cell lines, derived from human lung (A549), breast (MDA-MB-231), cervical (KB3-1) and colon (SW480) cancers, using the MTT cytotoxicity assay; (ii) antioxidant activity, analyzed by measuring the scavenging activity of DPPH radicals; (iii) lipase inhibitory activity, determined from the hydrolytic reaction of p-nitrophenyllaurate with pancreatic lipase; and (iv) antimicrobial activity against three Gram-positive and two Gram-negative bacteria species plus one strain of yeast using the disc-diffusion method and determination of the minimum inhibitory concentration by the broth micro-dilution assay.

Results

The crude dichloromethane and/or ethanol extracts from four plant species showed an effective in vitro cytotoxic activity against the human cancer cell lines that was broadly similar to that of the specific chemotherapy drugs (etoposide, doxorubicin, vinblastine and oxaliplatin). In particular, this is the first report of the strong in vitro cytotoxic activity of Bauhinia strychnifolia vines. The tested tissue parts of only six plant species (Allium sativum, Cocoloba uvifera, Dolichandrone spathacea, Lumnitzera littorea, Sonneratia alba and Sonneratia caseolaris) showed promising potential antioxidant activity, whereas lipase inhibitory activity was only found in the ethanol extract from Coscinum fenestratum and this was weak at 17-fold lower than Orlistat, a known lipase inhibitor. The highest antimicrobial activity was observed in the extracts from S. alba and S. caseolaris against Pseudomonas aeruginosa and Candida albicans, respectively.

Conclusion

The Thai medicinal plant B. strychnifolia is first reported to exert strong in vitro cytotoxic activities against human cancer cell lines and warrants further enrichment and characterization. The broad spectrum of the biological activities from the studied plant extracts can be applied as the guideline for the selection of Thai medicinal plant species for further pharmacological and phytochemical investigations.
Does the presence of a pharmacist in primary care clinics improve diabetes medication adherence?
Authors: Kocarnik Beverly Mielke , Liu Chuan-Fen , Wong Edwin S , Perkins Mark , Maciejewski Matthew L , Yano Elizabeth M , Au David H , Piette John D , Bryson Chris L
Published: November 2012

Background

Although oral hypoglycemic agents (OHAs) are an essential element of therapy for the management of type 2 diabetes, OHA adherence is often suboptimal. Pharmacists are increasingly being integrated into primary care as part of the move towards a patient-centered medical home and may have a positive influence on medication use. We examined whether the presence of pharmacists in primary care clinics was associated with higher OHA adherence.

Methods

This retrospective cohort study analyzed 280,603 diabetes patients in 196 primary care clinics within the Veterans Affairs healthcare system. Pharmacists presence, number of pharmacist full-time equivalents (FTEs), and the degree to which pharmacy services are perceived as a bottleneck in each clinic were obtained from the 2007 VA Clinical Practice Organizational Survey—Primary Care Director Module. Patient-level adherence to OHAs using medication possession ratios (MPRs) were constructed using refill data from administrative pharmacy databases after adjusting for patient characteristics. Clinic-level OHA adherence was measured as the proportion of patients with MPR >= 80%. We analyzed associations between pharmacy measures and clinic-level adherence using linear regression.

Results

We found no significant association between pharmacist presence and clinic-level OHA adherence. However, adherence was lower in clinics where pharmacy services were perceived as a bottleneck.

Conclusions

Pharmacist presence, regardless of the amount of FTE, was not associated with OHA medication adherence in primary care clinics. The exact role of pharmacists in clinics needs closer examination in order to determine how to most effectively use these resources to improve patient-centered outcomes including medication adherence.
Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance
Authors: Wang Wei , Li Qing , Yang Tao , Bai Guang , Li Dongsheng , Li Qiang , Sun Hongzhi
Published: November 2012

Background

The aquaporins (AQPs) are a family of small membrane transport proteins whose overexpression has been implicated in tumorigenesis. However, the expression of AQP5 and AQP8 in colorectal cancer and the clinical significance remain unexplored. This study aimed to detect the expression of AQP5 and AQP8 in clinical samples of colorectal cancer and analyze the correlations of their expression with the clinicopathological features of colorectal cancer.

Methods

Forty pairs of colorectal cancer tissue and paraneoplastic normal tissue were obtained at the time of surgery from patients with colorectal cancer. The expression of AQP5 and AQP8 was detected by immunohistochemical staining and reverse transcriptase polymerase chain reaction.

Results

AQP5 was mainly expressed in colorectal carcinoma cells and barely expressed in paraneoplastic normal tissues. By contrast, AQP8 was mainly expressed in paraneoplastic normal tissues and barely expressed in colorectal carcinoma cells. AQP5 expression was not significantly associated with the sex or age of the patient with colorectal cancer (P>0.05), but was closely associated with the differentiation, tumor-nodes-metastasis stage and distant lymph node metastasis of colorectal carcinoma (P<0.05).

Conclusions

AQP5 might be a novel prognostic biomarker for patients with colorectal cancer.
JAK-STAT1/3-Induced Expression of Signal Sequence-Encoding Proopiomelanocortin mRNA in Lymphocytes Reduces Inflammatory Pain in Rats
Authors: Busch-Dienstfertig Melanie , Labuz Dominika , Wolfram Theresa , Vogel Nicole N , Stein Christoph
Published: November 2012

Background:

Proopiomelanocortin (POMC)-derived beta-endorphin1-31 from immune cells can inhibit inflammatory pain. Here we investigated cytokine signaling pathways regulating POMC gene expression and beta-endorphin production in lymphocytes to augment such analgesic effects.

Results:

Interleukin-4 dose-dependently elevated POMC mRNA expression in naïve lymph node-derived cells in vitro, as determined by real-time PCR. This effect was neutralized by janus kinase (JAK) inhibitors. Transfection of Signal Transducer and Activator of Transcription (STAT) 1/3 but not of STAT6 decoy oligonucleotides abolished interleukin-4 induced POMC gene expression. STAT3 was phosphorylated in in vitro interleukin-4 stimulated lymphocytes and in lymph nodes draining inflamed paws in vivo. Cellular beta-endorphin increased after combined stimulation with interleukin-4 and concanavalin A. Consistently, in vivo reduction of inflammatory pain by passively transferred T cells improved significantly when donor cells were pretreated with interleukin-4 plus concanavalin A. This effect was blocked by naloxone-methiodide.

Conclusion:

Interleukin-4 can amplify endogenous opioid peptide expression mediated by JAK-STAT1/3 activation in mitogen-activated lymphocytes. Transfer of these cells leads to inhibition of inflammatory pain via activation of peripheral opioid receptors.
Accelerated large volume irradiation with dynamic Jaw/Dynamic Couch Helical Tomotherapy
Authors: Krause Sonja , Beck Sebastian , Schubert Kai , Lissner Steffen , Hui Susanta , Herfarth Klaus , Debus Juergen , Sterzing Florian
Published: November 2012

Background

Helical Tomotherapy (HT) has unique capacities for the radiotherapy of large and complicated target volumes. Next generation Dynamic Jaw/Dynamic Couch HT delivery promises faster treatments and reduced exposure of organs at risk due to a reduced dose penumbra.

Methods

Three challenging clinical situations were chosen for comparison between Regular HT delivery with a field width of 2.5 cm (Reg 2.5) and 5.0 cm (Reg 5.0) and DJDC delivery with a maximum field width of 5.0 cm (DJDC 5.0): Hemithoracic Irradiation, Whole Abdominal Irradiation (WAI) and Total Marrow Irradiation (TMI). For each setting, five CT data sets were chosen, and target coverage, conformity, integral dose, dose exposure of organs at risk (OAR) and treatment time were calculated.

Results

Both Reg 5.0 and DJDC 5.0 achieved a substantial reduction in treatment time while maintaining similar dose coverage. Treatment time could be reduced from 10:57 min to 3:42 min / 5:10 min (Reg 5.0 / DJDC 5.0) for Hemithoracic Irradiation, from 18:03 min to 8:02 min / 8:03 min for WAI and to 18:25 min / 18:03 min for TMI. In Hemithoracic Irradiation, OAR exposure was identical in all modalities. For WAI, Reg 2.5 resulted in lower exposure of liver and bone. DJDC plans showed a small but significant increase of ∼ 1 Gy to the kidneys, the parotid glans and the thyroid gland. While Reg 5.0 and DJDC were identical in terms of OAR exposure, integral dose was substantially lower with DJDC, caused by a smaller dose penumbra.

Conclusions

Although not clinically available yet, next generation DJDC HT technique is efficient in improving the treatment time while maintaining comparable plan quality.
Fluorescence in situ hybridization as adjunct to cytology improves the diagnosis and directs estimation of prognosis of malignant pleural effusions
Authors: Han Jingquan , Cao Shouqiang , Zhang Kai , Zhao Guibin , Xin Yanzhong , Dong Qing , Yan Yubo , Cui Jian
Published: November 2012

Background

The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity and specificity. The aim of this study was to investigate the value of fluorescence in situ hybridization (FISH) as adjuncts to conventional cytologic examination in patients with malignant pleural effusions.

Methods

We conducted a retrospective cohort study of 93 inpatients with pleural effusions (72 malignant pleural effusions metastatic from 11 different organs and 21 benign) over 23 months. All the patients came from Chinese northeast areas. Aspirated pleural fluid underwent cytologic examination and fluorescence in situ hybridization (FISH) for aneuploidy. We used FISH in single-colour or if appropriate in dual-colour evaluation to detect chromosomal aberrations (chromosomes 7, 11, and 17) in effusion cells as markers of malignancy, to raise the diagnostic yield and identified the efficiency by diagnostic biopsy. Predominant cytogenetic anomalies and patterns of intratumor cytogenetic heterogeneity were brought in relation to overall survival rate.

Results

Cytology alone confirmed malignant pleural effusions in 45 of 72 patients (sensitivity 63%), whereas FISH alone positively identified 48 of 72 patients (sensitivity 67%). Both tests had high specificity in predicting benign effusions. If cytology and FISH were considered together, they exhibited 88% sensitivity and 94.5% specificity in discriminating benign and malignant effusions. Combined, the two assays were more sensitive than either test alone. Although the positive predictive value of each test was 94.5%, the negative predictive value of cytology and FISH combined was 78%, better than 47% and 44% for FISH and cytology alone, respectively. There was a significantly prolonged survival rate for patients with aneuploidy for chromosome 17.

Conclusions

FISH in combination with conventional cytology is a highly sensitive and specific diagnostic tool for detecting malignant cells in pleural effusions . The high sensitivity and specificity may be associated with geographic area and race. Simple numeric FISH anomalies may be prognostic.