bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurohormonal Regulation of Cardiac Histone Deacetylase 5 Nuclear Localization by Phosphorylation-Dependent and Phosphorylation-Independent Mechanisms
Authors: Haworth Robert S. , Stathopoulou Konstantina , Candasamy Alexandra J. , Avkiran Metin
Published: May 2012

Rationale:

Myocyte enhancer factor 2 (MEF2) transcription factors drive the genetic reprogramming that precipitates pathological cardiac hypertrophy and remodeling. Class II histone deacetylase (HDAC) isoforms, such as HDAC5, act as signal-responsive repressors of MEF2 activity in cardiac myocytes and their nuclear export provides a key mechanism for the neurohormonal induction of such activity.

Objective:

To delineate the mechanism(s) through which 2 clinically relevant neurohormonal stimuli, endothelin-1 (ET1) and the β-adrenergic receptor (β-AR) agonist isoproterenol (ISO), may regulate HDAC5 nuclear localization in adult cardiac myocytes.

Methods and Results:

ET1 induced HDAC5 phosphorylation and nuclear export in ventricular myocytes from the adult rat heart. Use of a novel, highly selective protein kinase D (PKD) inhibitor and a nonphosphorylatable HDAC5 mutant revealed that PKD-mediated phosphorylation was necessary for ET1-induced HDAC5 nuclear export. In contrast, ISO reduced HDAC5 phosphorylation in the presence or absence of ET1 but still induced HDAC5 nuclear export. ISO-induced HDAC5 nuclear export occurred through a β
1
-AR–mediated oxidative process that was independent of PKD, protein kinase A, and Ca
2+
/calmodulin-dependent kinase II activities. Although ET1 and ISO shared a similar ability to induce HDAC5 nuclear export, albeit through distinct phosphorylation-dependent versus phosphorylation-independent mechanisms, ISO induced a significantly greater increase in MEF2 activity.

Conclusions:

PKD-mediated HDAC5 phosphorylation and nuclear export are unlikely to be of major importance in regulating MEF2-driven cardiac remodeling in the presence of sympathetic activity with intact β
1
-AR signaling, which would not only counteract HDAC5 phosphorylation but also induce HDAC5 nuclear export through a novel phosphorylation-independent, oxidation-mediated mechanism. Inhibition of this mechanism may contribute to the therapeutic efficacy of β
1
-AR antagonists in heart failure.
Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5
Authors: Chen Jenny X. , Krane Markus , Deutsch Marcus-Andre , Wang Li , Rav-Acha Moshe , Gregoire Serge , Engels Marc C. , Rajarajan Kuppusamy , Karra Ravi , Abel E. Dale , Wu Joe C. , Milan David , Wu Sean M.
Published: May 2012

Rationale:

Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown.

Objective:

To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT).

Methods and Results:

We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes.

Conclusions:

Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy.
Ethnic Identity and Anti-Semitism: Tadeusz Słobodzianek Stages the Polish Taboo
Authors: Lease Bryce
Published: May 2012

Tadeusz Słobodzianek's play, Our Class, addresses the 1941 massacre in the village of Jedwabne, Poland, where an estimated 1,600 local Jews were rounded up by their neighbors, locked inside a barn, and burned to death. First staged in London at the Royal National Theatre in 2009, and later remounted at Teatr na Woli in Warsaw, the play investigates the relationship between anti-Semitism and Polish national identity, exploring how theatre can shape our understanding of history.
Theatre's Heterotopia and the Site-Specific Production ofSuitcase
Authors: Tompkins Joanne
Published: May 2012

The site-specific performance Suitcase was staged at Liverpool Street Station, London, for one day only to commemorate the 70th anniversary of the Kindertransport. In its attempts to expand historical and theatrical space, and expand audience, the play creates a new kind of heterotopia that gestures beyond the physical site of the performance.
“Brand China” on the World Stage: Jingju, the Olympics, and Globalization
Authors: Evans Megan
Published: May 2012

Leading up to the 2008 Beijing Olympics, multinational corporations such as McDonald's exploited jingju (Beijing opera) as an internationally legible marker of “Chinese-ness.” Though jingju received muddled exposure in the Olympics opening ceremony, post-Olympic deployments prove it persists as a central component of an emerging “Brand China” that emphasizes the synthesis of traditional and 21st-century elements.
Performance Art at the (Virginia) Margins: Anthony Restivo's Far Off and All Aflame
Authors: Sargent Carey , Thompson Rachel , Hsu Wendy
Published: May 2012

In a small college town in western Virginia, writer Anthony Restivo searches for unmediated honesty through his very public endurance art. In the midst of media attention, misinformation, and his physical struggle to complete a 22-day piece, Restivo creates fleeting moments of intimacy in the town's first known work of performance art.
Counseling Health Psychology
Authors: Raque-Bogdan Trisha L. , Torrey Carrie L. , Lewis Brian L. , Borges Nicole J.
Published: May 2012

Training directors of American Psychological Association–approved counseling psychology doctoral programs completed a questionnaire assessing (a) student and faculty involvement in health-related research, practice, and teaching; (b) health-related research conducted by students and faculty; and (c) programs’ expectations and ability to increase health training opportunities. Statistical comparisons suggest that a high frequency of programs name health psychology as an area of emphasis, offer specialized health psychology training, and provide health-psychology-related practica. Many reported faculty and student interest and involvement in health psychology training and research. Yet few faculty in these programs identified themselves as counseling health psychologists. Results suggest that there is interest in health psychology within counseling psychology training programs but that only a minority of programs has developed structured curricula in the area. Given counseling psychology’s unique emphasis on prevention, well-being, multiculturalism, and social justice, counseling psychology programs are well suited to developing counseling health psychology curricula.
Meaning and Usage of a Term for Bullying-Like Phenomena in South Korea
Authors: Lee Seungha , Smith Peter K. , Monks Claire P.
Published: May 2012

This study investigates the meaning and usage of the term wang-ta and other terms for bullying-like phenomena in an Eastern culture, South Korea. Data were obtained from 113 participants, ranging from young children to adults. Age-related differences in usage were found, in part developmental, but also suggesting some recent historical changes perhaps due to fashion in usage of terms especially in adolescence. Nevertheless, the term wang-ta and related terms all emphasize social exclusion, and this is argued to reflect the collectivistic nature of South Korean society.
Using the Actor–Partner Interdependence Model to Study the Effects of Group Composition
Authors: Kenny David A. , Garcia Randi L.
Published: May 2012

We extend the actor–partner interdependence model (APIM), a model originally proposed for the analysis of dyadic data, to the study of groups. We call this extended model the group actor–partner interdependence model or GAPIM. For individual outcomes (e.g., satisfaction with the group), we propose a group composition model with four effects; for group-level outcomes (e.g., group productivity), we propose a model with two effects; and for dyad-level outcomes (e.g., liking of each of the other members of the group), a model with seven effects. For instance, for an individual outcome with gender as the group composition variable the effects are gender of the actor, gender of the other group members, actor similarity in gender to the others in the group, and the others’ similarity in gender. For each of these models, we discuss the ways in which different submodels map onto social-psychological processes. We illustrate the GAPIM with two data sets.
‘In the name of love’
Authors: Tang Lijun
Published: May 2012

This article examines a group of Chinese seafarer-partners’ activities in an online support group and discusses how gender issues may serve to influence women’s informal learning process online. It reveals that seafarer-partners not only acquired information, knowledge and emotional support, but also learnt an attitude, which helped them to adapt to the environment. In this process, gendered communication content and style and gendered beliefs/values played a role.
Effect of high pressure rolling on weld-induced residual stresses
Authors: Coules H E , Colegrove P , Cozzolino L D , Wen S W , Ganguly S , Pirling T
Published: May 2012

The formation of large residual stresses continues to be a problematic side effect of all common welding processes. In this work, localised high pressure rolling of gas metal arc welds to relieve these residual stresses has been investigated using strain gauging and neutron diffraction. Rolling was found to remove undesirable tensile stresses and even induce large compressive ones, though only when applied after rather than during welding. Strain measurements taken during combined welding and rolling operations show that this is because material at the weld line continues to yield as it cools. This erases any beneficial effect on the stress distribution of rolling at high temperature. A method of rolling using an oscillating force is also presented and found to be just as effective as the equivalent static force process.
Nanoindentation of explosive polymer composites to simulate deformation and failure
Authors: Yeager J. D. , Ramos K. J. , Singh S. , Rutherford M. E. , Majewski J. , Hooks D. E.
Published: May 2012

Crack initiation and propagation is a common concern for molecular composites such as plastic bonded explosives (PBXs) and pharmaceutical tablets. Under compressive stresses, cracks form at contacts between crystals and propagate along crystal-binder interfaces, causing composite failure. To investigate this process, crystal-binder interfaces have been characterised and their mechanical properties tested. Here, samples were created with interfaces representative of those in PBXs and characterised with surface energy measurements and neutron reflectometry (NR). Nanoindentation was performed to simulate the deformation and cracking that occurs at crystal–crystal contacts through the binder. NR revealed that use of a plasticiser disrupts typical crystal–binder intermixing and results in a mechanically weaker interface. During nanoindentation, a plasticised binder was observed by atomic force microscopy to delaminate around indentation impressions, whereas a non-plasticised binder did not. Differences in interfacial adhesion and incompatible strain, dictated by the elastic–plastic film compliances, were used to explain the contrasting delamination behaviours.
Mechanism of misorientation development within coalesced martensite
Authors: Pak J H , Bhadeshia H K D H , Karlsson L
Published: May 2012

Coarse crystals of martensite can form by the coalescence of thin individual platelets of martensite under appropriate circumstances. Although these coarse grains are essentially single crystals, there exist significant orientation gradients across their dimensions. It is demonstrated that these gradients arise because of the plasticity induced in austenite due to the transformation strain associated with martensite growth. The resulting localised change in austenite orientation is then inherited by the new martensite growth, which consumes the deformed austenite.
Influence of quenching rate and composition on optimal annealing temperature of Nd–Fe–B based nanocrystalline hard magnetic alloys
Authors: Huyen N T T , Yen N H , Thanh P T , Huu D T , Thuy D M , Thuy N M , Dan N H
Published: May 2012

A number of Nd–Fe–B based nanocrystalline hard magnetic alloys such as Nd4–xPrxFe78B18 ( x = 0, 2 and 4), (Nd0·5Pr0·5)xNb1·5Fe88·5–xB10 ( x = 6, 8, 10 and 12), Nd10·5–xCoxNb3Fe80·5B6 ( x = 0, 2, 4 and 6), Nd10·5NbxFe83·5–xB6 ( x = 1·5 and 3) were prepared by melt spinning and subsequently annealing. The relationships between quenching rate, composition and the annealing temperature of the alloys were investigated systematically to obtain optimal fabrication conditions. For each quenching rate and each composition, an optimal annealing temperature could be found in a range from 650 to 750°C so that the nanocrystalline magnetic phases are formed optimally leading to an enhancement of the coercivity and maximum energy product of the alloys. The variation trend of influence of quenching rate and composition on the optimal annealing temperature of the alloys is presented and discussed.
Healing behaviour of creep induced cavities during hot isostatic pressing of nickel based superalloy
Authors: Zhou Y , Zhang Z , Zhao Z H , Zhong Q P
Published: May 2012

The evolution of morphological characteristics associated with creep induced cavities in a cast polycrystalline superalloy under various hot isostatic pressing conditions was investigated. Concentrically oriented N type γ′ rafting structures near the sintering cavities were formed during sintering. The stress gradient causing a chemical potential gradient around the cavity plays a dominant role in solute diffusion, resulting in the nucleation and continuous growth of the solid solution on the cavity surface to achieve healing.
Surface dislocation nucleation by wedge indenter contacts
Authors: Zhao J. , Ma L. F. , Korsunsky A. M.
Published: May 2012

Dislocation nucleation from a surface in contact with a rigid wedge indenter is studied in the framework of plane strain. First, the equivalent driving force on a singularity is derived in compact form. Using the result obtained, the driving force is then expressed in the form of complex integral formulae in terms of the Kolosov–Muskhelishvili potentials for wedge contacts. Then, by the Rice–Thomson model, a dislocation nucleation criterion is proposed for a surface loaded in contact, from which we obtain the critical contact size (equivalently, the critical contact load) and the dislocation emission angles at the different wedge indenter apex angles. Finally, the results are discussed, and conclusions are drawn.
Mechanical properties of YSZ thermal barrier coatings with segmented structure
Authors: Wang Y , Li M X , Suo H L
Published: May 2012

Traditional and modified Y2O3 stabilised zirconia (YSZ) thermal barrier coatings (TBCs) on nicked based superalloy DZ125 were produced by atmospheric plasma spray. In addition to the thermal properties, the mechanical properties of ceramics are also very important for superior TBCs. The mechanical properties of the sprayed coatings at room temperature, including microhardness, Young's modulus, fracture toughness and tensile strength, were evaluated. The Young's modulus and microhardness of the segmented coating were measured to be about 72 and 8 GPa, relatively higher than those of the non-segmented coating respectively. The fracture toughness was determined by an indentation technique. The values of 1·7–2·0 MPa m1/2 for the traditional YSZ coatings are relatively lower than the values for the modified YSZ coatings 2·0–2·3 MPa m1/2. The lower porosity and better lamellar bonding of the segmented coating could be responsible for the improvement of the mechanical properties.
The complement receptor 2/factor H fusion protein TT30 protects paroxysmal nocturnal hemoglobinuria erythrocytes from complement-mediated hemolysis and C3 fragment opsonization
Authors: Risitano Antonio M. , Notaro Rosario , Pascariello Caterina , Sica Michela , del Vecchio Luigi , Horvath Christopher J. , Fridkis-Hareli Masha , Selleri Carmine , Lindorfer Margaret A. , Taylor Ronald P. , Luzzatto Lucio , Holers V. Michael
Published: May 2012

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis because of the lack from erythrocyte surface of the complement regulators CD55 and CD59, with subsequent uncontrolled continuous spontaneous activation of the complement alternative pathway (CAP), and at times of the complement classic pathway. Here we investigate in an in vitro model the effect on PNH erythrocytes of a novel therapeutic strategy for membrane-targeted delivery of a CAP inhibitor. TT30 is a 65 kDa recombinant human fusion protein consisting of the iC3b/C3d-binding region of complement receptor 2 (CR2) and the inhibitory domain of the CAP regulator factor H (fH). TT30 completely inhibits in a dose-dependent manner hemolysis of PNH erythrocytes in a modified extended acidified serum assay, and also prevents C3 fragment deposition on surviving PNH erythrocytes. The efficacy of TT30 derives from its direct binding to PNH erythrocytes; if binding to the erythrocytes is disrupted, only partial inhibition of hemolysis is mediated by TT30 in solution, which is similar to that produced by the fH moiety of TT30 alone, or by intact human fH. TT30 is a membrane-targeted selective CAP inhibitor that may prevent both intravascular and C3-mediated extravascular hemolysis of PNH erythrocytes and warrants consideration for the treatment of PNH patients.
ICOS-LICOS interaction is critically involved in TGN1412-mediated T-cell activation
Authors: Weissmüller Sabrina , Semmler Linda Y. , Kalinke Ulrich , Christians Stefan , Müller-Berghaus Jan , Waibler Zoe
Published: May 2012

TGN1412, a superagonistic CD28-specific antibody, was shown to require Fc-cross-linking or immobilization as a prerequisite to mediate T-cell proliferation and cytokine release in vitro. We used primary human umbilical vein endothelial cells (HUVECs) to study their ability to induce activation of TGN1412-treated T cells. We confirmed that peripheral primary human T cells do not show activation upon stimulation with soluble TGN1412 alone. Nevertheless, cocultivation of TGN1412-treated T cells with HUVECs induced T-cell activation that was further enhanced using cytokine prestimulated HUVECs. Unexpectedly, Fc-FcγR interaction was dispensable for endothelial cell–mediated proliferation of TGN1412-treated T cells. Transwell-culture assays showed that TGN1412-treated T cells need direct cell-to-cell contact to HUVECs to induce proliferation. We found that costimulatory ICOS-LICOS interaction between T cells and endothelial cells is critically involved in TGN1412-mediated effects. Blocking LICOS reduced TGN1412-mediated T-cell proliferation significantly, whereas recombinant LICOS fully conferred TGN1412-mediated T-cell proliferation. Of note, cytokine stimulation enhanced LICOS expression on HUVECs and ICOS-LICOS interaction up-regulated ICOS expression on TGN1412-treated T cells. Hence, we provide a model of positive feedback conferred by ICOS-LICOS interaction between TGN1412-treated T cells and endothelial cells.
Dynamic antibody-binding properties in the pathogenesis of HIT
Authors: Sachais Bruce S. , Litvinov Rustem I. , Yarovoi Serge V. , Rauova Lubica , Hinds Jillian L. , Rux Ann H. , Arepally Gowthami M. , Poncz Mortimer , Cuker Adam , Weisel John W. , Cines Douglas B.
Published: May 2012

Rapid laboratory assessment of heparin-induced thrombocytopenia (HIT) is important for disease recognition and management. The utility of contemporary immunoassays to detect antiplatelet factor 4 (PF4)/heparin antibodies is hindered by detection of antibodies unassociated with disease. To begin to distinguish properties of pathogenic anti-PF4/heparin antibodies, we compared isotype-matched monoclonal antibodies that bind to different epitopes: KKO causes thrombocytopenia in an in vivo model of HIT, whereas RTO does not. KKO binding to PF4 and heparin is specifically inhibited by human HIT antibodies that activate platelets, whereas inhibition of RTO binding is not differentially affected. Heparin increased the avidity of KKO binding to PF4 without affecting RTO, but it did not increase total binding or binding to nontetrameric PF4K50E. Single-molecule forced unbinding demonstrated KKO was 8-fold more reactive toward PF4 tetramers and formed stronger complexes than RTO, but not to PF4K50E dimers. KKO, but not RTO, promoted oligomerization of PF4 but not PF4K50E. This study reveals differences in the properties of anti-PF4 antibodies that cause thrombocytopenia not revealed by ELISA that correlate with oligomerization of PF4 and sustained high-avidity interactions that may simulate transient antibody-antigen interactions in vivo. These differences suggest the potential importance of epitope specificity in the pathogenesis of HIT.
Bridging knowledge translation gap in health in developing countries: visibility, impact and publishing standards in journals from the Eastern Mediterranean
Authors: Utrobičić Ana , Chaudhry Nauman , Ghaffar Abdul , Marušić Ana
Published: May 2012

Background

Local and regional scientific journals are important factors in bridging gaps in health knowledge translation in low-and middle-income countries. We assessed indexing, citations and publishing standards of journals from the Eastern Mediterranean region.

Methods

For journals from 22 countries in the collection of the Index Medicus for the Eastern Mediterranean Region (IMEMR), we analyzed indexing in bibliographical databases and citations during 2006–2009 to published items in 2006 in Web of Science (WoS) and SCOPUS. Adherence to editorial and publishing standards was assessed using a special checklist.

Results

Out of 419 journals in IMEMR, 19 were indexed in MEDLINE, 23 in WoS and 46 in SCOPUS. Their impact factors ranged from 0.016 to 1.417. For a subset of 175 journals with available tables of contents from 2006, articles published in 2006 from 93 journals received 2068 citations in SCOPUS (23.5% self-citations) and articles in 86 journals received 1579 citations in WoS (24.3% self-citations) during 2006–2009. Citations to articles came mostly from outside of the Eastern Mediterranean region (76.8% in WoS and 75.4% in SCOPUS). Articles receiving highest number of citations presented topics specific for the region. Many journals did not follow editorial and publishing standards, such addressing requirements about the patient’s privacy rights (68.0% out of 244 analyzed), policy on managing conflicts of interest (66.4%), and ethical conduct in clinical and animal research (66.4%).

Conclusion

Journals from the Eastern Mediterranean are visible in and have impact on global scientific community. Coordinated effort of all stakeholders in journal publishing, including researchers, journal editors and owners, policy makers and citation databases, is needed to further promote local journals as windows to the research in the developing world and the doors for valuable regional research to the global scientific community.
Decreased survival among lung cancer patients with co-morbid tuberculosis and diabetes
Authors: Shieh Shwn-Huey , Probst Janice C , Sung Fung-Chang , Tsai Wen-Chen , Li Ya-Shin , Chen Chih-Yi
Published: May 2012

Background

Comorbid conditions influence the survival of cancer patients. This study evaluated the influence of comorbidity on survival among lung cancer patients.

Methods

The authors evaluated the medical records of 1111 lung cancer patients of a medical center in Taiwan. Days of survival were calculated for each patient and mortality hazard ratios were estimated for associations with demographic status, comorbidity and cancer stage at diagnosis.

Results

On average, the survival time was slightly longer among women than among men (838 ± 689 vs. 749 ± 654 days, p = 0.050). Survival days increased with age (from 580 ± 526 [≤ 50 years] to 803 ± 693 [≥ 71 years] days, p = 0.020) and decreased with stage (from 1224 ± 656 [stage I] to 489 ± 536 [stage IV] days, p < 0.001). Younger patients were more likely to be diagnosed with lung cancer at a late stage. Compared with lung cancer patients without tuberculosis, those with tuberculosis had a significantly shorter average survival duration (584 vs. 791 days, p = 0.002) and a higher mortality hazard ratio (1.30, 95% CI: 1.03 - 1.65). A similar trend was observed in lung cancer patients with diabetes.

Conclusions

Lung cancer patients with comorbid tuberculosis or diabetes are at an elevated risk of mortality. These patients deserve greater attention while undergoing cancer treatment.
Adherence to a Mediterranean diet in Morocco and its correlates: cross-sectional analysis of a sample of the adult Moroccan population
Authors: El Rhazi Karima , Nejjari Chakib , Romaguera Dora , Feart Catherine , Obtel Majdouline , Zidouh Ahmed , Bekkali Rachid , Gateau Pascale Barberger
Published: May 2012

Background

Dietary habits in Morocco are changing and the causes are not well understood. This study aimed to analyse socio-demographic factors associated with adherence to the Mediterranean diet (MeDi) in a national random sample of the adult Moroccan population.

Methods

The data collected in this cross-sectional survey included socio-demographic factors and a food frequency questionnaire. MeDi adherence was assessed in 2214 individuals with complete dietary data. MeDi adherence was measured according to a simplified MeDi score based on the weekly frequency of intake of eight food groups (vegetables, legumes, fruits, cereal or potatoes, fish, red meat, dairy products and olive oil) with the use of the sex specific medians of the sample as cut-offs. A value of 0 or 1 was assigned to consumption of each component according to its presumed detrimental or beneficial effect on health. Logistic regression was used to estimate the association between MeDi adherence (low score 1-4 vs. high 5-8) and other factors.

Results

Mean age of the sample was 41.4 (standard deviation 15.3) years, 45.4% were men and 29.9% had a low MeDi adherence. Married subjects (adjusted odds ratio ORa=0.68, 95% CI 0.55-0.84) were less likely to have a low MeDi adherence compared to single, divorced or widowed persons. Persons from rural areas (ORa=1.46, 95% CI: 1.02-2.08), were more often low MeDi adherents compared to those from urban areas. Obese persons (ORa=1.56, 95% CI: 1.16-2.11) were more prone to low MeDi adherence than normal weight individuals.

Conclusion

MeDi is far from being a universal pattern in the Moroccan population. Intervention strategies should be implemented in target groups to maintain the traditional MeDi pattern considered as the original diet in Morocco.
Socioeconomic inequalities in mortality from conditions amenable to medical interventions: do they reflect inequalities in access or quality of health care?
Authors: Plug Iris , Hoffmann Rasmus , Artnik Barbara , Bopp Matthias , Borrell Carme , Costa Giuseppe , Deboosere Patrick , Esnaola Santi , Kalediene Ramune , Leinsalu Mall , Lundberg Olle , Martikainen Pekka , Regidor Enrique , Rychtarikova Jitka , Strand Björn Heine , Wojtyniak Bogdan , Mackenbach Johan P
Published: May 2012

Background

Previous studies have reported large socioeconomic inequalities in mortality from conditions amenable to medical intervention, but it is unclear whether these can be attributed to inequalities in access or quality of health care, or to confounding influences such as inequalities in background risk of diseases. We therefore studied whether inequalities in mortality from conditions amenable to medical intervention vary between countries in patterns which differ from those observed for other (non-amenable) causes of death. More specifically, we hypothesized that, as compared to non-amenable causes, inequalities in mortality from amenable causes are more strongly associated with inequalities in health care use and less strongly with inequalities in common risk factors for disease such as smoking.

Methods

Cause-specific mortality data for people aged 30–74 years were obtained for 14 countries, and were analysed by calculating age-standardized mortality rates and relative risks comparing a lower with a higher educational group. Survey data on health care use and behavioural risk factors for people aged 30–74 years were obtained for 12 countries, and were analysed by calculating age-and sex-adjusted odds ratios comparing a low with a higher educational group. Patterns of association were explored by calculating correlation coefficients.

Results

In most countries and for most amenable causes of death substantial inequalities in mortality were observed, but inequalities in mortality from amenable causes did not vary between countries in patterns that are different from those seen for inequalities in non-amenable mortality. As compared to non-amenable causes, inequalities in mortality from amenable causes are not more strongly associated with inequalities in health care use. Inequalities in mortality from amenable causes are also not less strongly associated with common risk factors such as smoking.

Conclusions

We did not find evidence that inequalities in mortality from amenable conditions are related to inequalities in access or quality of health care. Further research is needed to find the causes of socio-economic inequalities in mortality from amenable conditions, and caution should be exercised in interpreting these inequalities as indicating health care deficiencies.
B cell analysis of ethnic groups in Mali with differential susceptibility to malaria
Authors: Portugal Silvia , Doumtabe Didier , Traore Boubacar , Miller Louis H , Troye-Blomberg Marita , Doumbo Ogobara K , Dolo Amagana , Pierce Susan K , Crompton Peter D
Published: May 2012

Background

Several studies indicate that people of the Fulani ethnic group are less susceptible to malaria compared to those of other ethnic groups living sympatrically in Africa, including the Dogon ethnic group. Although the mechanisms of this protection remain unclear, the Fulani are known to have higher levels of Plasmodium falciparum-specific antibodies of all Ig classes as compared to the Dogon. However, the proportions of B cell subsets in the Fulani and Dogon that may account for differences in the levels of Ig have not been characterized.

Methods

In this cross-sectional study, venous blood was collected from asymptomatic Fulani (n = 25) and Dogon (n = 25) adults in Mali during the malaria season, and from P. falciparum-naïve adults in the U.S. (n = 8). At the time of the blood collection, P. falciparum infection was detected by blood-smear in 16% of the Fulani and 36% of the Dogon volunteers. Thawed lymphocytes were analysed by flow cytometry to quantify B cell subsets, including immature and naïve B cells; plasma cells; and classical, activated, and atypical memory B cells (MBCs).

Results

The overall distribution of B cell subsets was similar between Fulani and Dogon adults, although the percentage of activated MBCs was higher in the Fulani group (Fulani: 11.07% [95% CI: 9.317 – 12.82]; Dogon: 8.31% [95% CI: 6.378 – 10.23]; P = 0.016). The percentage of atypical MBCs was similar between Fulani and Dogon adults (Fulani: 28.3% [95% CI: 22.73 – 34.88]; Dogon: 29.3% [95% CI: 25.06 – 33.55], but higher than U.S. adults (U.S.: 3.0% [95% CI: -0.21 - 6.164]; P < 0.001). Plasmodium falciparum infection was associated with a higher percentage of plasma cells among Fulani (Fulani infected: 3.3% [95% CI: 1.788 – 4.744]; Fulani uninfected: 1.71% [95% CI: 1.33 – 2.08]; P = 0.011), but not Dogon adults.

Conclusion

These data show that the malaria-resistant Fulani have a higher percentage of activated MBCs compared to the Dogon, and that P. falciparum infection is associated with a higher percentage of plasma cells in the Fulani compared to the Dogon, findings that may account for the higher levels of P. falciparum antibodies in the Fulani.
Numerical test concerning bone mass apposition under electrical and mechanical stimulus
Authors: Garzón-Alvarado Diego A , Ramírez-Martínez Angélica M , Cardozo de Martínez Carmen Alicia
Published: May 2012

This article proposes a model of bone remodeling that encompasses mechanical and electrical stimuli. The remodeling formulation proposed by Weinans and collaborators was used as the basis of this research, with a literature review allowing a constitutive model evaluating the permittivity of bone tissue to be developed. This allowed the mass distribution that depends on mechanical and electrical stimuli to be obtained. The remaining constants were established through numerical experimentation. The results demonstrate that mass distribution is altered under electrical stimulation, generally resulting in a greater deposition of mass. In addition, the frequency of application of an electric field can affect the distribution of mass; at a lower frequency there is more mass in the domain. These numerical experiments open up discussion concerning the importance of the electric field in the remodeling process and propose the quantification of their effects.
Clinical guidelines contribute to the health inequities experienced by individuals with intellectual disabilities
Authors: Mizen Lindsay AM , Macfie Marjorie L , Findlay Linda , Cooper Sally-Ann , Melville Craig A
Published: May 2012

Background

Clinical practice guidelines are developed to improve the quality of healthcare. However, clinical guidelines may contribute to health inequities experienced by disadvantaged groups. This study uses an equity lens developed by the International Clinical Epidemiology Network (INCLEN) to examine how well clinical guidelines address inequities experienced by individuals with intellectual disabilities.

Methods

Nine health problems relevant to the health inequities experienced by persons with intellectual disabilities were selected. Clinical guidelines on these disorders were identified from across the world. The INCLEN equity lens was used as the basis for a purpose-designed, semistructured data collection tool. Two raters independently examined each guideline and completed the data collection tool. The data extracted by each rater were discussed at a research group consensus conference and agreement was reached on a final equity lens rating for each guideline.

Results

Thirty-six guidelines were identified, one of which (2.8%) explicitly excluded persons with intellectual disabilities. Of the remaining 35, six (17.1%) met the first criterion of the equity lens, identifying persons with intellectual disabilities at high risk for the specific health problem. Eight guidelines (22.9%) contained any content on intellectual disabilities. Six guidelines addressed the fourth equity lens criterion, by giving specific consideration to the barriers to implementation of the guideline in disadvantaged populations. There were no guidelines that addressed the second, third, and fifth equity lens criteria.

Conclusions

The equity lens is a useful tool to systematically examine whether clinical guidelines address the health needs and inequities experienced by disadvantaged groups. Clinical guidelines are likely to further widen the health inequities experienced by persons with intellectual disabilities, and other disadvantaged groups, by being preferentially advantageous to the general population. There is a need to systematically incorporate methods to consider disadvantaged population groups into the processes used to develop clinical guidelines.
Synthesis of naringin 6"-ricinoleate using immobilized lipase
Authors: Almeida Verônica M , Branco Carla RC , Assis Sandra A , Vieira Ivo JC , Braz-Filho Raimundo , Branco Alexsandro
Published: May 2012

Background

Naringin is an important flavanone with several biological activities, including antioxidant action. However, this compound shows low solubility in lipophilic preparations, such as is used in the cosmetic and food industries. One way to solve this problem is to add fatty acids to the flavonoid sugar unit using immobilized lipase. However, there is limited research regarding hydroxylation of unsaturated fatty acids as an answer to the low solubility challenge. In this work, we describe the reaction of naringin with castor oil containing ricinoleic acid, castor oil's major fatty acid component, using immobilized lipase from Candida antarctica. Analysis of the 1H and 13 C NMR (1D and 2D) spectra and literature comparison were used to characterise the obtained acyl derivative.

Results

After allowing the reaction to continue for 120 hours (in acetone media, 50°C), the major product obtained was naringin 6″-ricinoleate. In this reaction, either castor oil or pure ricinoleic acid was used as the acylating agent, providing a 33% or 24% yield, respectively. The chemical structure of naringin 6″-ricinoleate was determined using NMR analysis, including bidimensional (2D) experiments.

Conclusion

Using immobilized lipase from C. antarctica, the best conversion reaction was observed using castor oil containing ricinoleic acid as the acylating agent rather than an isolated fatty acid.

Graphical abstract

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A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy
Authors: Hallett Robin M , Pond Gregory , Hassell John A
Published: May 2012

Background

The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available.

Methods

We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents.

Results

Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol.

Conclusions

Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.
Low pressure hyperbaric oxygen therapy and SPECT brain imaging in the treatment of blast-induced chronic traumatic brain injury (post-concussion syndrome) and post traumatic stress disorder: a case report
Authors: Harch Paul G , Fogarty Paul G , Staab Paul K , Van Meter Keith
Published: May 2012

A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.
Unusual histological presentation in neurofibromas: Two case reports
Authors: Joshi Deepti , Gangane Nitin , Kishore Sanjeev , Vagha Sunita
Published: May 2012

Various histological variants of neurofibroma have been described. The objective of this paper is to discuss the unusual histological findings seen in two cases of neurofibromas associated with neurofibromatosis type 1 Both cases presented with multiple subcutaneous nodules. Surgical excision of the largest nodule was done in both the cases. Histological examination of case no.1 revealed a benign tumor of the peripheral nerve sheath, of neurofibroma type with presence of mucus producing glands. The epithelial component was benign in this case. The second case showed presence of rosettes in between areas of typical neurofibroma.
Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report
Authors: Mashitani Tsuyoshi , Yoshiji Hitoshi , Yamazaki Masaharu , Ikenaka Yasuhide , Noguchi Ryuichi , Ishikawa Masatoshi , Kawaratani Hideto , Matsuo Norihide , Uemura Masahito , Yamao Junichi , Fujimoto Masao , Mitoro Akira , Toyohara Masahisa , Yoshida Motoyuki , Sawai Masayoshi , Morioka Chie , Tsujimoto Tatsuhiro , Kitade Mitsuteru , Kaji Kosuke , Aihara Yosuke , Fukui Hiroshi
Published: May 2012

Background

Although several recent reports have shown that hepatocellular carcinoma (HCC) developed in patients with chronic hepatitis C (CH-C) even after having a sustained virological response (SVR) to interferon (IFN) therapy, it is not common for HCC to develop more than 10 years after SVR.

Case presentation

A 73-year-old Japanese man with CH-C who achieved SVR to IFN therapy 13 years ago was admitted into our hospital because of huge multiple liver tumors along with marked elevation of the tumor markers. Several diagnostic modalities strongly suggested HCC, and we performed histopathological examination. After confirming the diagnosis as well-differentiated HCC, we successfully treated these tumors with intensive combination therapies.

Conclusion

Our report highlights the need for careful follow-up for more than 10 years even if the patients with CH-C achieve SVR to IFN therapy.
Differences in adhesion and protrusion properties correlate with differences in migration speed under EGF stimulation
Authors: Hou Yue , Hedberg Sarah , Schneider Ian C
Published: May 2012

Background

Cell migration plays an essential role in many biological processes, such as cancer metastasis, wound healing and immune response. Cell migration is mediated through protrusion and focal adhesion (FA) assembly, maturation and disassembly. Epidermal growth factor (EGF) is known to enhance migration rate in many cell types; however it is not known how FA maturation, FA dynamics and protrusion dynamics are regulated during EGF-induced migration. Here we use total internal reflection fluorescence (TIRF) microscopy and image analysis to quantify FA properties and protrusion dynamics under different doses of EGF stimulation.

Results

EGF was found to broaden the distribution of cell migration rates, generating more fast and slow cells. Furthermore, groups based on EGF stimulation condition or cell migration speed were marked by characteristic signatures. When data was binned based on EGF stimulation conditions, FA intensity and FA number per cell showed the largest difference among stimulation groups. FA intensity decreased with increasing EGF concentration and FA number per cell was highest under intermediate stimulation conditions. No difference in protrusion behavior was observed. However, when data was binned based on cell migration speed, FA intensity and not FA number per cell showed the largest difference among groups. FA intensity was lower for fast migrating cells. Additionally, waves of protrusion tended to correlate with fast migrating cells.

Conclusions

Only a portion of the FA properties and protrusion dynamics that correlate with migration speed, correlate with EGF stimulation condition. Those that do not correlate with EGF stimulation condition constitute the most sensitive output for identifying why cells respond differently to EGF. The idea that EGF can both increase and decrease the migration speed of individual cells in a population has particular relevance to cancer metastasis where the microenvironment can select subpopulations based on some adhesion and protrusion characteristics, leading to a more invasive phenotype as would be seen if all cells responded like an “average” cell.
p53tumor suppressor gene mutations in fibroblast-like synoviocytes from erosion synovium and non-erosion synovium in rheumatoid arthritis
Authors: Yamanishi Yuji , Boyle David L , Green Douglas R , Keystone Edward C , Connor Alison , Zollman Susan , Firestein Gary S
Published: May 2012

Abnormalities in the p53 tumor suppressor gene have been detected in rheumatoid arthritis (RA) and could contribute to the pathogenesis of chronic disease. To determine whether synoviocytes from invasive synovium in RA have an increased number of mutations compared with non-erosion synoviocytes, p53 cDNA subclones from fibroblast-like synoviocytes (FLS) derived from erosion and non-erosion sites of the same synovium were examined in patients requiring total joint replacement. Ten erosion FLS lines and nine non-erosion FLS lines were established from nine patients with RA. Exons 5–10 from 209 p53 subclones were sequenced (114 from erosion FLS, 95 from non-erosion FLS). Sixty percent of RA FLS cell lines and 8.6% of the p53 subclones isolated from FLS contained p53 mutations. No significant differences were observed between the erosion and non-erosion FLS with regard to the frequency or type of p53 mutation. The majority of the mutations were missense transition mutations, which are characteristic of oxidative damage. In addition, paired intact RA synovium and cultured FLS from the same joints were evaluated for p53 mutations. Matched synovium and cultured synoviocytes contained p53 mutations, although there was no overlap in the specific mutations identified in the paired samples. Clusters of p53 mutations in subclones were detected in some FLS, including one in codon 249, which is a well-recognized 'hot spot' associated with cancer. Our data are consistent with the hypothesis that p53 mutations are randomly induced by genotoxic exposure in small numbers of RA synoviocytes localized to erosion and non-erosion regions of RA synovium. The determining factor for invasiveness might be proximity to bone or cartilage rather than the presence of a p53 mutation.