bluuebunny/crossref_metadata_2025 huggingface dataset:
The Absence of State Consent to Advisory Opinions of the International Court of Justice: Judicial and Political Restraints
Authors: Aljaghoub Mahasen
Published: April 2010

The International Court of Justice (ICJ) is the principal judicial organ of the United Nations, (UN) and its Statute is an integral part of the UN's Charter. The court's integral role within the UN has largely been misunderstood especially in the way the court has viewed its advisory jurisdiction. The ICJ always asserts that the delivery of an advisory opinion represents its participation in the UN's work and thus, in the absence of compelling reasons, a request for an opinion ought not to be refused. Some commentators note that the principle that the ICJ must participate in the work of the Organisation might sometimes conflict with its judicial character, which might result in not embracing the philosophy of “judicial restraint” in the court's advisory jurisdiction. They also contend that the absence of consent in advisory cases has led the court to overlook its judicial restraint. This article argues that those commentators have overlooked the main role of the ICJ's advisory function in clarifying the law and providing guidance for future action by the UN organs, and has consequently called for applying the principle of consent as a condition for giving an advisory opinion on questions relating to disputes pending between States. In the present article, the

Legal Consequences of the Construction of a Wall in the Occupied Palestinian Territory

opinion is analysed to see whether the absence of Israeli consent has undermined the ICJ's judicial character. The author is of the view that the court, as the principal judicial organ of the UN, should, by a cautious judicial policy, provide enlightenment to the UN and participate to achieving its goals while at the same time adhering to its judicial character.
Does social identity theory underlie relational demography? A test of the moderating effects of uncertainty reduction and status enhancement on similarity effects
Authors: Goldberg Caren B , Riordan Christine , Schaffer Bryan S
Published: April 2010

Relational demography research has its roots in social identity theory. However, prior research has not directly tested the effects of the two primary motives of social identification; uncertainty reduction and status enhancement. In this study, we examined the moderating effects of these motives on the relationship between demographic similarity and individuals’ affective reactions toward their work group. Uncertainty reduction, which we operationalized as self-continuity, moderated the relationship between race similarity and cohesiveness. In addition, status enhancement moderated both race and gender similarity effects on the group outcomes. We discuss implications of our findings for theory and research.
SPEECH: Seize the Day!
Authors: Wong D.T.
Published: April 2010

Good afternoon. I am David Wong, President-elect of the American Association for Dental Research, and it’s my pleasure to welcome you to the 2010 joint Annual Meetings of the AADR and the Canadian Association for Dental Research. I would like to extend a special welcome to our new members and the students who are joining us this year. I hope that each of you finds the next few days informative and stimulating.

There has never been a more important time for health care professionals to gather to discuss what we do and how we do it . . . because there has never been a time when health care has been so much in the forefront of our minds as individuals and as a nation. It is critical for us to ensure that we, as oral health specialists, are part of that conversation, because our research is increasingly being recognized as a key to unlocking not just oral and craniofacial diseases, but systemic issues as well. It is now abundantly clear that while oral and craniofacial abnormalities make up one piece of the body’s complex puzzle, they are, in many ways, a mirror of the entire system.

Just as we have learned that each part of the body has an effect on the entire system, we are also realizing that there is no one-size-fits-all way to diagnose and treat diseases. Both in our own field of dentistry and in other disciplines, individualized medicine is certain to be one of the most important concepts in health care research in the coming years.

Dr. Francis Collins, the new Director of NIH, authored a Policy Forum article in the January issue of Science for “Opportunities for Research and NIH”, where he detailed five areas of opportunity he sees as holding particular promise for NIH: high-throughput technologies, translational medicine, benefiting health care reform, focusing more on global health, and reinvigorating and empowering the biomedical research community. These are the opportunities we need to seize to advance oral health research, dentistry and global health.

Thank you all for being here. I hope that each of you will come away from this week with new information about the breakthroughs our colleagues are making . . . and a renewed dedication to the important contributions we are making to the health of our nation and the world.
St Paul’s Conversion: The Aesthetic Organization of Labour
Authors: Sørensen Bent M.
Published: April 2010

This paper compares the Italian Renaissance painter Caravaggio’s two versions of the Conversion of Saint Paul (1600/1601) with two modern models of organization. These comparisons show how organization is produced in art through ‘aesthetic landscaping’ (Gagliardi 2006), and in particular how these artistic reproductions convey certain images of the appropriate modern, entrepreneurial self and regimes of organization. The painting was originally commissioned by the Catholic Church, but it rejected the first and accepted the second version. The paper claims that this strategy strengthens the given organization of the Church and the Church’s strategic influence on the believers that adore the painting. But this all comes with a price, namely, the production of a number of strict divisions: in the accepted version, Paul becomes a pure transcendent spirit. Isolated from his surroundings, his servant and his horse, he is cut off from the very event of conversion. The rejected version harbours radically different, transgressive images of subjectivity, collectivity and entrepreneurship. By identifying these images, the paper contributes to the development of a critical approach to organizational aesthetics.
The Pathways From Parents’ Marital Quality to Adolescents’ School Adjustment in South Korea
Authors: Jeong Yu-Jin , Chun Young-Ju
Published: April 2010

This study tested the hypothesized pathways from parents’ marital quality to Korean adolescents’ school adjustment through the perception of self and parent—child relations. Based on previous literature and two major family theories, the authors hypothesized a path model to explain the process of how parents’ marital quality influenced school adjustment through child’s self-esteem and parent—child communication. The path model analysis was used with 578 Korean adolescent students in academic high schools. The results showed that Korean youth were likely to better adjust to a school setting as they perceived that their parents had a good marital relationship. The interparental relationship directly affected school adjustment but not psychological adjustment of self-esteem. Additionally, the marital quality of parents had an indirect effect on Korean youth’s school adjustment in the mediation process of parent—child communication. Academic and practical implications are also discussed, followed by limitations and future directions.
TightRope Versus Fiber Mesh Tape Augmentation of Acromioclavicular Joint Reconstruction
Authors: Zooker Chad C. , Parks Brent G. , White Kacey L. , Hinton Richard Y.
Published: April 2010

Background: The standard Weaver-Dunn reconstruction of the acromioclavicular (AC) joint does not provide adequate superoinferior or anteroposterior stability. Augmentation methods such as tape cerclage have been described. A new method of augmentation with the Arthrex TightRope is available.

Hypothesis: A Weaver-Dunn reconstruction augmented with the TightRope will provide superior superoinferior and anteroposterior stability to the AC joint as compared with a Weaver-Dunn reconstruction augmented with Mersilene fiber tape cerclage.

Study Design: Controlled laboratory study.

Methods: Six matched pairs of cadaveric shoulders underwent Weaver-Dunn AC joint reconstructions and were randomly assigned to receive either the TightRope device or tape cerclage augmentation. Translation in 2 planes was measured in the intact state under load and after 1 load cycle and 2000 load cycles.

Results: TightRope-augmented repair showed less superoinferior translation (mean ± standard error) than cerclage-augmented repair in initially repaired (1.6 ± 0.1 mm vs 5.0 ± 1.1 mm, P = 0.03) and cyclically loaded (2.1 ± 0.1 mm vs 5.8 ± 1.2 mm, P = 0.02) conditions. TightRope repairs were stiffer than the native ligaments in the superoinferior plane. Less anteroposterior translation was observed with TightRope versus cerclage augmentation (initially repaired, 6.8 ± 0.4 mm vs 18.8 ± 2.6 mm, P < 0.001; cycled, 15.0 ± 1.4 mm vs 28.3 ± 2.7 mm, P = 0.01), but neither method maintained normal anteroposterior laxity after 1500 cycles compared with the intact state.

Conclusion: Superoinferior and anteroposterior translation with TightRope augmentation was lower than with tape cerclage.

Clinical Relevance: TightRope augmentation of a Weaver-Dunn procedure could provide increased protection for AC joint reconstruction, allowing for earlier mobilization and more aggressive early rehabilitation. The potential clinical effect of additional tightening in the superoinferior direction beyond that of the native joint remains an issue for further study.
Comparison of Single- and Double-Bundle Anterior Cruciate Ligament Reconstructions in Restoration of Knee Kinematics and Anterior Cruciate Ligament Forces
Authors: Seon Jong Keun , Gadikota Hemanth R. , Wu Jia-Lin , Sutton Karen , Gill Thomas J. , Li Guoan
Published: April 2010

Background: Anterior cruciate ligament (ACL) deficiency alters 6 degrees of freedom knee kinematics, yet only anterior translation and internal rotation have been the primary measures in previous studies.

Purpose: To compare the 6 degrees of freedom knee kinematics and the graft forces after single- and double-bundle ACL reconstructions under various external loading conditions.

Study Design: Controlled laboratory study.

Methods: Ten human cadaveric knees were tested with a robotic testing system under 4 conditions: intact, ACL deficient, single-bundle reconstructed with a quadrupled hamstring tendon graft, and double-bundle reconstructed with 2 looped hamstring tendon grafts. Knee kinematics and forces of the ACL or ACL graft in each knee were measured under 3 loading conditions: an anterior tibial load of 134 N, a simulated quadriceps muscle load of 400 N, and combined tibial torques (10 N·m valgus and 5 N·m internal tibial torques) at 0°, 15°, 30°, 60°, and 90° of knee flexion.

Results: The double-bundle reconstruction restored the anterior and medial laxities closer to the intact knee than the single-bundle reconstruction. However, the internal rotation of the tibia under the simulated quadriceps muscle load was significantly decreased when compared with the intact knee after both reconstructions, more so after double-bundle reconstruction ( P < .05). The entire graft force of the double-bundle reconstruction was more similar to that of the intact ACL than that of the single-bundle reconstruction. However, the posterolateral bundle graft in the double-bundle reconstructed knee was overloaded as compared with the intact posterolateral bundle.

Conclusion: The double-bundle reconstruction can better restore the normal anterior-posterior and medial-lateral laxities than the single-bundle reconstruction can, but an overloading of the posterolateral bundle graft can occur in a double-bundle reconstructed knee.

Clinical relevance: Both single-bundle and double-bundle techniques cannot restore the rotational laxities and the ACL force distributions of the intact knee.
Maturity and hygiene quality of composts and hygiene indicators in agricultural soil fertilised with municipal waste or manure compost
Authors: Tontti Tiina , Heinonen-Tanski Helvi , Karinen Päivi , Reinikainen Olli , Halinen Arja
Published: April 2010

Composts produced from municipal source separated biowaste (Biowaste), a mixture of biowaste and anaerobically digested sewage sludge (Biosludge) and cattle manure (Manure) were examined for their maturity and hygiene quality. The composts were applied to a potato crop in 2004 and to a barley nurse crop of forage ley in 2005 in a field experiment. Numbers of faecal coliforms, enterococci, clostridia and Salmonella in field soil were determined 2 weeks and 16 weeks after compost applications. Municipal compost batches chosen based on successful processing showed variable maturity during field application, and the need to evaluate compost maturity with multiple variables was confirmed. The numbers of faecal coliform were similar in all compost types, averaging 4.7 and 2.3 log 10 CFU g-1 in the first and second years, respectively. The highest number of enterococci was 5.2 log10 CFU g-1, found in Manure compost in the first year, while the highest clostridia numbers were found in Biosludge compost, averaging 4.0 log10 CFU g -1 over both years. Except for one case, less than 2.4 log10 CFU g-1 of faecal coliforms or clostridia were found in compost-fertilised soil, while the numbers of enterococci were mostly higher than in unfertilised soil (<4.2 or <3.2 log10 CFU g-1, respectively). No hygiene indicator bacteria were present in compost-fertilised potato at harvest. Overall, compost fertilisations caused rather small changes in the counts of hygiene indicators in the field environment.
Bias From Wireless Substitution in Surveys of Hispanics
Authors: Dutwin David , Keeter Scott , Kennedy Courtney
Published: April 2010

Increasingly, American households are choosing to forgo ownership of landline telephones in favor of cell phones. Presently, more than 25% of Hispanics now only own a cell phone. Concern about potential bias from noncoverage of this “cell-only” population in traditional general population RDD (random digit dial) telephone interviewing has been a particular focus among the survey research community. Because Hispanics lead all ethnic and racial groups in the percentage who are now cell-only, it is critical to understand the impact this has on research of Hispanics, which to date is still largely accomplished using traditional landline telephone survey methods. This article explores the extent to which noncoverage of cell-only Hispanics leads to raw bias in landline telephone surveys of Hispanics and the degree to which survey weights may correct for such bias.
Dynamics of Student Cognitive-Affective Transitions During a Mathematics Game
Authors: Rodrigo Ma. Mercedes T.
Published: April 2010

Researchers of interactive learning environments have grown increasingly interested in designing these systems to become more responsive to differences in students’ cognitive-affective states. They believe that the detection of and adaptation to student cognition and affect may boost student learning gains and enhance the quality of students’ overall learning experience. A growing body of research focuses specifically on the study of cognitive-affective dynamics, defined as the natural ways in which a student’s cognitive-affective states change over time. These types of studies help designers identify desirable (virtuous) cycles that they want to foster and undesirable (vicious) cycles that they want to dissuade. In this study, the author examined the dynamics of the cognitive-affective states exhibited by Filipino students as they used the pre-algebra game MATH BLASTER 9-12. The author focused on the cognitive-affective states of boredom, confusion, delight, engagement, frustration, neutrality, and surprise. Using quantitative field observations, the author determined which of these states tended to persist or transition into other states over time. It was found that boredom was the only state that tended to persist. Boredom tended not to lead to engagement. Students who were confused were not likely to stay confused but were likely to transition into engagement. Students who were delighted were not likely to become confused. From these findings and based on comparisons with related work, it is concluded that boredom is a persistent and undesirable state. Confusion is not persistent and is desirable because it leads to further engagement with the content.
Weighted Voting in the United Nations Security Council
Authors: Strand Jonathan R. , Rapkin David P.
Published: April 2010

Various observers have proposed weighted voting as part of an overhaul of the UN Security Council. This article employs game-theoretic methods to simulate the effects of weighting votes in the UN Security Council according to the ability of individual states, as well as on the ability of the Council to act. The authors first briefly review reform proposals. Drawing on recent proposals, they then calculate voting weights based on population, contributions to the UN, and a measure of sovereign equality. These component measures are assigned different weights in order to formulate three sets of weighted votes. After this, they define several measures of voting power that can be used to assess voting power in weighted voting systems. The measures used in this article assess the relative voting power of individual members as well as the probability the Council will engage in collective action to pass a resolution. Results of voting power simulations are then presented under both simple and qualified majority rules. The authors’ simulations indicate that under weighted voting the capacity of the Council to act is likely to increase under most conditions unless high qualified majorities are required. The simulations also demonstrate that the main problem identified with weighted voting—large deviations between voting weight and voting power—are not present in the weighted voting systems analyzed here.
Magnetised intragastric foreign body collection and autism
Authors: Rashid Farhan , Davies Laura , Iftikhar S.Y.
Published: April 2010

The pica phenomenon, where non-edible substances are repeatedly consumed, has been linked with developmental and behavioural disorders, particularly autism. The clinical presentation of foreign body ingestion in patients with autism is discussed, and recommendations for caregivers are provided based on the available literature. An 18-year-old man with severe autism and behavioural difficulties presented with a vague history of decreased appetite and melaena of eight months duration. Foreign body ingestion commonly occurs in individuals with autism spectrum disorders and should be suspected in patients who present with vague gastrointestinal symptoms. The adverse medical and surgical consequences of foreign body ingestion emphasize the need for early recognition. Surgical intervention for foreign body ingestion can prevent complications. Magnetic substances can cause considerable gastrointestinal morbidity and require urgent endoscopic or surgical removal. Primary prevention is also vital.
Effects of Oral Rivastigmine on Cognitive Domains in Mild-to-Moderate Alzheimer’s Disease
Authors: Farlow Martin R. , Cummings Jeffrey L. , Olin Jason T. , Xiangyi Meng
Published: April 2010

Rivastigmine has beneficial effects on cognitive functioning in Alzheimer’s disease (AD). Effects of cholinesterase inhibitors, particularly rivastigmine, on AD Assessment Scale—cognitive subscale (ADAS-cog) domains and individual items have rarely been analyzed. Results from 4 randomized, double-blind, placebo-controlled, 26-week rivastigmine capsule trials in patients with mild-to-moderate AD were pooled and ADAS-cog domains and individual items were evaluated. Data were available from 878, 1053, and 863 patients in the 1 to 4 mg/d, 6 to 12 mg/d, and placebo groups, respectively. Rivastigmine-treated groups were superior to placebo on total ADAS-cog and memory domain scores (P ≤ .0001). Rivastigmine 6 to 12 mg/d was also significantly better versus placebo on language (P < .001) and praxis (P < .001); greatest treatment responses were seen on memory items (P < .0001). Although rivastigmine was associated with dose-dependent improvements in all cognitive domains, largest effects were on memory items. Evaluation of ADAS-cog domain scores provides insight into test items most likely to respond to treatment.
Do Undergraduates and MBAs Differ Online?: Initial Conclusions From the Literature
Authors: Arbaugh J.B.
Published: April 2010

To date, online learning research in business and management education generally assumes that degree program level does not affect effective online learning practice. However, the few studies that have examined both undergraduate and graduate business students have found differences in the learning outcomes of those groups. Because research samples tend to be exclusively either graduate or undergraduate students, researchers and practitioners of online business education are left to speculate regarding potential differences between these student populations. This article reviews the online business and management education literature and proposes differences between undergraduate and graduate business students and courses based on student and instructor characteristics, course design characteristics, technological characteristics, and preferences for and performance in courses delivered at least partially online, relative to classroom-based courses. Some of the primary conclusions from the review are that consideration of learning styles, student demographics, and perceptions of the course management system are more important in undergraduate online courses, and that ensuring effective participant interaction is a larger issue for instructors and course design in graduate online courses. The article concludes with preliminary recommendations for researchers, instructors, instructional designers, and degree program directors for developing and designing courses that are suited appropriately to these student populations.
Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome
Authors: Sanz Miguel A. , Montesinos Pau , Rayón Chelo , Holowiecka Alexandra , de la Serna Javier , Milone Gustavo , de Lisa Elena , Brunet Salut , Rubio Vicente , Ribera José M. , Rivas Concha , Krsnik Isabel , Bergua Juan , González José , Díaz-Mediavilla Joaquín , Rojas Rafael , Manso Félix , Ossenkoppele Gert , González José D. , Lowenberg Bob
Published: April 2010

A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMA LPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 × 109/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high- risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278.
Pulmonary hypertension and nitric oxide depletion in sickle cell disease
Authors: Bunn H. Franklin , Nathan David G. , Dover George J. , Hebbel Robert P. , Platt Orah S. , Rosse Wendell F. , Ware Russell E.
Published: April 2010

During the past decade a large body of experimental and clinical studies has focused on the hypothesis that nitric oxide (NO) depletion by plasma hemoglobin in the microcirculation plays a central role in the pathogenesis of many manifestations of sickle cell disease (SCD), particularly pulmonary hypertension. We have carefully examined those studies and believe that the conclusions drawn from them are not adequately supported by the data. We agree that NO depletion may well play a role in the pathophysiology of other hemolytic states such as paroxysmal nocturnal hemoglobinuria, in which plasma hemoglobin concentrations are often at least an order of magnitude greater than in SCD. Accordingly, we conclude that clinical trials in SCD designed to increase the bioavailability of NO or association studies in which SCD clinical manifestations are related to plasma hemoglobin via its surrogates should be viewed with caution.
Rural health centres, communities and malaria case detection in Zambia using mobile telephones: a means to detect potential reservoirs of infection in unstable transmission conditions
Authors: Kamanga Aniset , Moono Petros , Stresman Gillian , Mharakurwa Sungano , Shiff Clive
Published: April 2010

Background

Effective malaria control depends on timely acquisition of information on new cases, their location and their frequency so as to deploy supplies, plan interventions or focus attention on specific locations appropriately to intervene and prevent an upsurge in transmission. The process is known as active case detection, but because the information is time sensitive, it is difficult to carry out. In Zambia, the rural health services are operating effectively and for the most part are provided with adequate supplies of rapid diagnostic tests (RDT) as well as effective drugs for the diagnosis and treatment of malaria. The tests are administered to all prior to treatment and appropriate records are kept. Data are obtained in a timely manner and distribution of this information is important for the effective management of malaria control operations. The work reported here involves combining the process of positive diagnoses in rural health centres (passive case detection) to help detect potential outbreaks of malaria and target interventions to foci where parasite reservoirs are likely to occur.

Methods

Twelve rural health centres in the Choma and Namwala Districts were recruited to send weekly information of rapid malaria tests used and number of positive diagnoses to the Malaria Institute at Macha using mobile telephone SMS. Data were entered in excel, expressed as number of cases per rural health centre and distributed weekly to interested parties.

Results

These data from each of the health centres which were mapped using geographical positioning system (GPS) coordinates were used in a time sensitive manner to plot the patterns of malaria case detection in the vicinity of each location. The data were passed on to the appropriate authorities. The seasonal pattern of malaria transmission associated with local ecological conditions can be seen in the distribution of cases diagnosed.

Conclusions

Adequate supplies of RDT are essential in health centres and the system can be expanded throughout the country to support strategic targeting of interventions by the National Malaria Control Programme. Participation by the health centre staff was excellent.
Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells
Authors: Cheung Chun Hei Antonio , Chen Huang-Hui , Cheng Li-Ting , Lyu Kevin W. , Kanwar Jagat R. , Chang Jang-Yang
Published: April 2010

Background

Survivin is a dual functioning protein. It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression.

Results

Here, we demonstrated that Hsp90 inhibitors, geldanamycin and 17-AAG, induced the over-expression of survivin in three different human cancer cell lines as shown by Western blotting. Increased survivin mRNA transcripts were observed in 17-AAG and geldanamycin-treated HT-29 and HONE-1 cancer cells. Interestingly, real-time PCR and translation inhibition studies revealed that survivin was over-expressed partially through the up-regulation of protein translation instead of gene transcription in A549 cancer cells. In addition, 17-AAG-treated A549, HONE-1 and HT-29 cells showed reduced proteasomal activity while inhibition of 26S proteasome activity further increased the amount of survivin protein in cells. At the functional level, down-regulation of survivin by siRNA further increased the drug sensitivity to 17-AAG in the tested cancer cell lines.

Conclusions

We showed for the first time that down-regulation of survivin is not a definite therapeutic function of Hsp90 inhibitors. Instead, targeting Hsp90 with small molecule inhibitors will induce the over-expression of survivin in certain cancer cell lines and subsequently enhances the ability of cell survival in drug-treated situations. The current study suggests that dual inhibition of Hsp90 and survivin may be warranted.
Association of LIPC -250G>A polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations
Authors: Meng Li , Ruixing Yin , Yiyang Li , Xingjiang Long , Kela Li , Wanying Liu , Lin Zhang , Weixiong Lin , Dezhai Yang , Shangling Pan
Published: April 2010

Background

The association between -250G>A polymorphism in the promoter region of the hepatic lipase gene (LIPC) and plasma high-density lipoprotein cholesterol (HDL-C) concentration is contradictory in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association ofLIPC-250G>A (rs2070895) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Methods

A total of 778 subjects of Bai Ku Yao and 648 participants of Han Chinese aged 15-80 were randomly selected from our previous stratified randomized cluster samples. Genotyping of theLIPC-250G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

Results

The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P< 0.01 for all). The frequencies of GG, GA and AA genotypes were 50.0%, 43.3% and 6.7% in Bai Ku Yao, and 35.7%, 50.6% and 13.7% in Han (P< 0.01); respectively. The frequencies of G and A alleles were 71.7% and 28.3% in Bai Ku Yao, and 61.0% and 39.0% in Han (P< 0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao were lower in GG genotype than in GA or AA genotype (P< 0.05-0.01). The levels of TC, HDL-C, LDL-C and ApoB in Han were lower in GG genotype than in GA or AA genotype (P< 0.05-0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao, and the levels of HDL-C, LDL-C and ApoB in Han were correlated with genotype and/or allele (P< 0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both ethnic groups.

Conclusions

The differences in the serum lipid profiles between the two ethnic groups might partly result from different genotypic frequency ofLIPC-250G>A or differentLIPC-enviromental interactions.
Quality of life in colon cancer patients with skin side effects: preliminary results from a monocentric cross sectional study
Authors: Andreis Federica , Rizzi Anna , Mosconi Paola , Braun Claudia , Rota Luigina , Meriggi Fausto , Mazzocchi Maria , Zaniboni Alberto
Published: April 2010

Background

Epidermal growth factor receptor inhibitors are widely prescribed anticancer drugs. Patients treated commonly develop dermatologic adverse drugs reactions, but rarely they are involved in systematic evaluation of their quality of life. This monocentric cross sectional study is carried out to assess quality of life in colon cancer patients experienced skin side effects due to anti epidermal growth factor receptor inhibitors therapy.

Methods

Consecutive patients with skin side effects to therapy treated at Fondazione Poliambulanza were enrolled in this study. Quality of life was evaluated with the Italian validated version of Skindex-29 questionnaire, exploring three dimensions: symptoms, emotional, and physical functioning. Skindex-29 was administered one time between the eighth and the twelfth week of the treatment.

Results

Forty-five consecutive patients, mainly with metastatic colon cancer (29 female, 16 male), with an average age of 59.31 years (ranging from 34-78) were included in the study and analyzed. Patients showed a great impact of skin side effects on symptoms (mean 43), followed by emotional (mean 30), and functioning (mean 26) scales. In general women, the 55-65 age class, and patients with partial remission reported the worst quality of life.

Conclusions

Epidermal growth factor receptor inhibitors' skin side effects have an important impact on quality of life in advanced colon cancer patients; symptoms scale is the most effect respect to emotional and functioning scales.
Systemic vasculopathy with altered vasoreactivity in a transgenic mouse model of scleroderma
Authors: Derrett-Smith Emma C , Dooley Audrey , Khan Korsa , Shi-wen Xu , Abraham David , Denton Christopher P
Published: April 2010

Introduction

Vasculopathy, including altered vasoreactivity and abnormal large vessel biomechanics, is a hallmark of systemic sclerosis (SSc). However, the pathogenic link with other aspects of the disease is less clear. To assess the potential role of transforming growth factor beta (TGF-β) overactivity in driving these cardiovascular abnormalities, we studied a novel transgenic mouse model characterized by ligand-dependent activation of TGF-β signaling in fibroblasts.

Methods

The transgenic mouse strain Tβ RIIΔk-fib is characterized by balanced ligand-dependent upregulation of TGF-β signaling. Aortic and cardiac tissues were examined with histologic, biochemical, and isolated organ bath studies. Vascular and perivascular architecture was examined by hematoxylin and eosin (H&E) and special stains including immunostaining for TGF-β1 and phospho-Smad2/3 (pSmad2/3). Confirmatory aortic smooth muscle cell proliferation, phenotype, and functional assays, including signaling responses to exogenous TGF-β and endothelin-1, were performed. Aortic ring contractile responses to direct and receptor-mediated stimulation were assessed.

Results

Aortic ring contractility and relaxation were diminished compared with wild-type controls, and this was associated with aortic adventitial fibrosis confirmed histologically and with Sircol assay. TGF-β1 and pSmad 2/3 expression was increased in the adventitia and smooth muscle layer of the aorta. Aortic smooth muscle cells from transgenic animals showed significant upregulation of TGF-β- responsive genes important for cytoskeletal function, such as transgelin and smoothelin, which were then resistant to further stimulation with exogenous TGF-β1. These cells promoted significantly more contraction of free floating type I collagen lattices when compared with the wild-type, but were again resistant to exogenous TGF-β1 stimulation. Aortic ring responses to receptor-mediated contraction were reduced in the transgenic animals. Specifically, bosentan reduced endothelin-mediated contraction in wild-type animals, but had no effect in transgenic animals, and endothelin axis gene expression was altered in transgenic animals. Transgenic mice developed cardiac fibrosis.

Conclusions

The histologic, biochemical, and functional phenotype of this transgenic mouse model of scleroderma offers insight into the altered biomechanical properties previously reported for large elastic arteries in human SSc and suggests a role for perturbed TGF-β and endothelin activity in this process.
Sex-Dependent Effects of Neonatal Inflammation on Adult Inflammatory Markers and Behavior
Authors: Kentner A. C. , McLeod S. A. , Field E. F. , Pittman Q. J.
Published: April 2010

Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 μg/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females.
Contribution of Mineralocorticoid and Glucocorticoid Receptors to the Chronotropic and Hypertrophic Actions of Aldosterone in Neonatal Rat Ventricular Myocytes
Authors: Rossier Michel F. , Python Magaly , Maturana Andrés D.
Published: April 2010

Mineralocorticoids and glucocorticoids have been involved in the genesis of ventricular arrhythmias associated with pathological heart hypertrophy. We previously observed, using isolated neonate rat ventricular cardiomyocytes, that both aldosterone (Aldo) and corticosterone induced in vitro a marked acceleration of the spontaneous contractions of these cells, a phenomenon dependent on the expression of the low threshold T-type calcium channels. Because both mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mediated the chronotropic response to corticosteroids, we characterized the role of each receptor using spironolactone and mifepristone (RU-486) as specific antagonists. We first observed that GR antagonism, but not MR antagonism, completely disrupted the significant correlation existing between the level of T channel mRNA and the beating frequency; this difference could not be explained by a specific regulation of channel expression or activity by one of the receptors. Moreover, the chronotropic action of Aldo was additive to that of forskolin, a direct activator of the cAMP pathway. This additive response was selectively abolished upon GR inhibition. Finally, myocyte hypertrophy induced in vitro by Aldo was completely prevented by GR antagonism, whereas spironolactone had only a marginal effect. These results suggest that, in isolated rat ventricular cardiomyocytes, the activation of both MR and GR is necessary for a complete electrical remodeling and a maximal chronotropic response to corticosteroids. However, GR alone appears involved in the sensitization of the cells to the chronotropic regulation through the cAMP pathway and in the hypertrophic response to steroids. These observations have therapeutic implications given the fact that MR becomes a major target of pharmacological drugs in the clinical practice for preventing cardiac function decompensation and evolution toward heart failure and lethal arrhythmias.
Vitamin D Deficiency in Mice Impairs Colonic Antibacterial Activity and Predisposes to Colitis
Authors: Lagishetty Venu , Misharin Alexander V. , Liu Nancy Q. , Lisse Thomas S. , Chun Rene F. , Ouyang Yi , McLachlan Sandra M. , Adams John S. , Hewison Martin
Published: April 2010

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D3 (2.5 ± 0.1 vs. 24.4 ± 1.8 ng/ml) and active 1,25-dihydroxyvitamin D3 (28.8 ± 3.1 vs. 45.6 ± 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 ± 0.85 vs. 1.57 ± 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.
Long-Term Treatment of 12 Children with Chronic Hypoparathyroidism: A Randomized Trial Comparing Synthetic Human Parathyroid Hormone 1-34 versus Calcitriol and Calcium
Authors: Winer Karen K. , Sinaii Ninet , Reynolds James , Peterson Donna , Dowdy Karen , Cutler Gordon B.
Published: April 2010

Context: Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. This is the first randomized controlled study in children comparing treatment with synthetic human PTH 1-34 and calcitriol.

Objective: The primary objective was to assess the efficacy and safety of long-term PTH 1-34 vs. calcitriol treatment in the maintenance of normal serum calcium values and renal calcium excretion in children with hypoparathyroidism.

Setting: The study was conducted at a clinical research center.

Subjects: Subjects included 12 children aged 5–14 yr with chronic hypoparathyroidism and without severe renal or hepatic insufficiency.

Study Design: The study was a 3-yr randomized parallel trial comparing twice-daily calcitriol (plus calcium and cholecalciferol in four daily doses) vs. sc PTH 1-34 treatment, with weekly or biweekly monitoring of serum and urine calcium.

Results: Mean predose serum calcium levels were maintained at, or just below, the normal range, and urine calcium levels remained in the normal range throughout the 3-yr study, with no significant differences between treatment groups. Creatinine clearance, corrected for body surface area, did not differ between groups and remained normal throughout the study. Markers of bone turnover were mildly elevated during PTH 1-34 therapy and remained within the normal range during calcitriol therapy. Mean bone mineral density Z-scores at the anterior-posterior lumbar spine, femoral neck, distal radius, and whole body remained within the normal range and did not differ between groups throughout the study. Similarly, height and weight percentiles did not differ between treatment groups and remained normal throughout the 3-yr follow-up.

Conclusion: We conclude that PTH 1-34 therapy is safe and effective in maintaining stable calcium homeostasis in children with hypoparathyroidism. Additionally, PTH 1-34 treatment allowed normal skeletal development because there were no differences in bone mineral accrual, linear growth, or weight gain between the two treatment arms over the 3-yr study period.
Protein phosphatase 2A cooperates with the autophagy-related kinase UNC-51 to regulate axon guidance inCaenorhabditis elegans
Authors: Ogura Ken-ichi , Okada Takako , Mitani Shohei , Gengyo-Ando Keiko , Baillie David L. , Kohara Yuji , Goshima Yoshio
Published: April 2010

UNC-51 is a serine/threonine protein kinase conserved from yeast to humans. The yeast homolog Atg1 regulates autophagy (catabolic membrane trafficking) required for surviving starvation. In C. elegans, UNC-51 regulates the axon guidance of many neurons by a different mechanism than it and its homologs use for autophagy. UNC-51 regulates the subcellular localization (trafficking) of UNC-5, a receptor for the axon guidance molecule UNC-6/Netrin; however, the molecular details of the role for UNC-51 are largely unknown. Here, we report that UNC-51 physically interacts with LET-92, the catalytic subunit of serine/threonine protein phosphatase 2A (PP2A-C), which plays important roles in many cellular functions. A low allelic dose of LET-92 partially suppressed axon guidance defects of weak, but not severe, unc-51 mutants, and a low allelic dose of PP2A regulatory subunits A (PAA-1/PP2A-A) and B (SUR-6/PP2A-B) partially enhanced the weak unc-51 mutants. We also found that LET-92 can work cell-non-autonomously on axon guidance in neurons, and that LET-92 colocalized with UNC-51 in neurons. In addition, PP2A dephosphorylated phosphoproteins that had been phosphorylated by UNC-51. These results suggest that, by forming a complex, PP2A cooperates with UNC-51 to regulate axon guidance by regulating phosphorylation. This is the first report of a serine/threonine protein phosphatase functioning in axon guidance in vivo.