bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycogen Synthase Kinase-3 Inhibition Induces Glioma Cell Death through c-MYC, Nuclear Factor-κB, and Glucose Regulation
Authors: Kotliarova Svetlana , Pastorino Sandra , Kovell Lara C. , Kotliarov Yuri , Song Hua , Zhang Wei , Bailey Rolanda , Maric Dragan , Zenklusen Jean Claude , Lee Jeongwu , Fine Howard A.
Published: August 2008

Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation and apoptosis. Its role in glioblastoma multiforme has yet to be elucidated. We identified GSK3 as a regulator of glioblastoma multiforme cell survival using microarray analysis and small-molecule and genetic inhibitors of GSK3 activity. Various molecular and genetic approaches were then used to dissect out the molecular mechanisms responsible for GSK3 inhibition–induced cytotoxicity. We show that multiple small molecular inhibitors of GSK3 activity and genetic down-regulation of GSK3α/β significantly inhibit glioma cell survival and clonogenicity. The potency of the cytotoxic effects is directly correlated with decreased enzyme activity–activating phosphorylation of GSK3α/β Y276/Y216 and with increased enzyme activity inhibitory phosphorylation of GSK3α S21. Inhibition of GSK3 activity results in c-MYC activation, leading to the induction of Bax, Bim, DR4/DR5, and tumor necrosis factor-related apoptosis-inducing ligand expression and subsequent cytotoxicity. Additionally, down-regulation of GSK3 activity results in alteration of intracellular glucose metabolism resulting in dissociation of hexokinase II from the outer mitochondrial membrane with subsequent mitochondrial destabilization. Finally, inhibition of GSK3 activity causes a dramatic decrease in intracellular nuclear factor-κB activity. Inhibition of GSK3 activity results in c-MYC–dependent glioma cell death through multiple mechanisms, all of which converge on the apoptotic pathways. GSK3 may therefore be an important therapeutic target for gliomas. Future studies will further define the optimal combinations of GSK3 inhibitors and cytotoxic agents for use in gliomas and other cancers. [Cancer Res 2008;68(16):6643–51]
Quantitative Control of Adaptive Cardiac Hypertrophy by Acetyltransferase p300
Authors: Wei Jian Qin , Shehadeh Lina A. , Mitrani James M. , Pessanha Monica , Slepak Tatiana I. , Webster Keith A. , Bishopric Nanette H.
Published: August 2008

Background—Acetyltransferase p300 is essential for cardiac development and is thought to be involved in cardiac myocyte growth through MEF2- and GATA4-dependent transcription. However, the importance of p300 in the modulation of cardiac growth in vivo is unknown.

Methods and Results—Pressure overload induced by transverse aortic coarctation, postnatal physiological growth, and human heart failure were associated with large increases in p300. Minimal transgenic overexpression of p300 (1.5- to 3.5-fold) induced striking myocyte and cardiac hypertrophy. Both mortality and cardiac mass were directly related to p300 protein dosage. Heterozygous loss of a single p300 allele reduced pressure overload–induced hypertrophy by ≈50% and rescued the hypertrophic phenotype of p300 overexpressers. Increased p300 expression had no effect on total histone deacetylase activity but was associated with proportional increases in p300 acetyltransferase activity and acetylation of the p300 substrates histone 3 and GATA-4. Remarkably, a doubling of p300 levels was associated with the de novo acetylation of MEF2. Consistent with this, genes specifically upregulated in p300 transgenic hearts were highly enriched for MEF2 binding sites.

Conclusions—Small increments in p300 are necessary and sufficient to drive myocardial hypertrophy, possibly through acetylation of MEF2 and upstream of signals promoting phosphorylation or nuclear export of histone deacetylases. We propose that induction of myocardial p300 content is a primary rate-limiting event in the response to hemodynamic loading in vivo and that p300 availability drives and constrains adaptive myocardial growth. Specific reduction of p300 content or activity may diminish stress-induced hypertrophy and forestall the development of heart failure.
Use of Cardiac Resynchronization Therapy in Patients Hospitalized With Heart Failure
Authors: Piccini Jonathan P. , Hernandez Adrian F. , Dai David , Thomas Kevin L. , Lewis William R. , Yancy Clyde W. , Peterson Eric D. , Fonarow Gregg C.
Published: August 2008

Background—

The frequency and characterization of patients receiving cardiac resynchronization therapy (CRT) are largely unknown since the publication of pivotal clinical trials and subsequent incorporation of CRT into the American College of Cardiology/American Heart Association guidelines for heart failure.

Methods and Results—

We analyzed 33 898 patients admitted from January 2005 through September 2007 to 228 hospitals participating in the American Heart Association’s Get With the Guidelines–Heart Failure program. There were 4201 patients (12.4%) discharged alive with CRT, including 811 new implants. Patients discharged with CRT were older (median age, 75 versus 72 years) and had lower median left ventricular ejection fraction (30% versus 38%), more frequent ischemic cardiomyopathy (58% versus 45%), more history of atrial fibrillation (38% versus 27%), and higher rates of β-blocker and aldosterone antagonist use (
P
<0.0001 for all) than those without CRT. We found that 4.8% of patients with left ventricular ejection fraction ≤35% were discharged with a new CRT implant, which varied greatly by hospital. Ten percent of patients discharged with a new CRT implant had a left ventricular ejection fraction >35%. Major factors associated with lower rates of new CRT placement were treatment in the northeast (odds ratio, 0.40; 95% confidence interval, 0.30 to 0.53), black race (odds ratio, 0.45; 95% confidence interval, 0.36 to 0.57), increasing left ventricular ejection fraction per 10% (odds ratio, 0.56; 95% confidence interval, 0.52 to 0.60), and increasing age per 10 years in those >70 years of age (odds ratio, 0.56; 95% confidence interval, 0.48 to 0.65).

Conclusions—

Although CRT is a recent evidence-based therapy for heart failure, patterns of use differ significantly from clinical trials and published guidelines. Important variations also exist for CRT therapy based on race, geographic region, comorbidities, and age and need to be addressed through further study and/or quality-of-care initiatives.
Primary Prevention of Stroke by Healthy Lifestyle
Authors: Chiuve Stephanie E. , Rexrode Kathryn M. , Spiegelman Donna , Logroscino Giancarlo , Manson JoAnn E. , Rimm Eric B.
Published: August 2008

Background—

The combination of healthy lifestyle factors is associated with lower risk of coronary heart disease, diabetes, and total cardiovascular disease. Little is known about the impact of multiple lifestyle factors on the risk of stroke.

Methods and Results—

We conducted a prospective cohort study among 43 685 men from the Health Professionals Follow-up Study and 71 243 women from the Nurses’ Health Study. Diet and other lifestyle factors were updated from self-reported questionnaires. We defined a low-risk lifestyle as not smoking, a body mass index <25 kg/m
2
, ≥30 min/d of moderate activity, modest alcohol consumption (men, 5 to 30 g/d; women, 5 to 15 g/d), and scoring within the top 40% of a healthy diet score. We documented 1559 strokes (853 ischemic, 278 hemorrhagic) among women and 994 strokes (600 ischemic, 161 hemorrhagic) among men during follow-up. Women with all 5 low-risk factors had a relative risk of 0.21 (95% confidence interval [CI], 0.12, 0.36) for total and 0.19 (95% CI, 0.09, 0.40) for ischemic stroke compared with women who had none of these factors. Among men, the relative risks were 0.31 (95% CI, 0.19, 0.53) for total and 0.20 (95% CI, 0.10, 0.42) for ischemic stroke for the same comparison. Among the women, 47% (95% CI, 18 to 69) of total and 54% (95% CI, 15 to 78%) of ischemic stroke cases were attributable to lack of adherence to a low-risk lifestyle; among the men, 35% (95% CI, 7 to 58) of total and 52% (95% CI, 19 to 75) of ischemic stroke may have been prevented.

Conclusion—

A low-risk lifestyle that is associated with a reduced risk of multiple chronic diseases also may be beneficial in the prevention of stroke, especially ischemic stroke.
The Relation of El Niño–Southern Oscillation (ENSO) to Winter Tornado Outbreaks
Authors: Cook A. R. , Schaefer J. T.
Published: August 2008

Winter tornado activity (January–March) between 1950 and 2003 was analyzed to determine the possible effect of seasonally averaged sea surface temperatures in the equatorial Pacific Ocean, the ENSO phase, on the location and strength of tornado outbreaks in the United States. Tornado activity was gauged through analyses of tornadoes occurring on tornado days (a calendar day featuring six or more tornadoes within the contiguous United States) and strong and violent tornado days (a calendar day featuring five or more tornadoes rated F2 and greater within the contiguous United States). The tornado days were then stratified according to warm (37 tornado days, 14 violent days), cold (51 tornado days, 28 violent days), and neutral (74 tornado days, 44 violent days) winter ENSO phase. It is seen that during winter periods of neutral tropical Pacific sea surface temperatures, there is a tendency for U.S. tornado outbreaks to be stronger and more frequent than they are during winter periods of anomalously warm tropical Pacific sea surface temperatures (El Niño). During winter periods with anomalously cool Pacific sea surface temperatures (La Niña), the frequency and strength of U.S. tornado activity lies between that of the neutral and El Niño phase. ENSO-related shifts in the preferred location of tornado activity are also observed. Historically, during the neutral phase, tornado outbreaks typically occurred from central Oklahoma and Kansas eastward through the Carolinas. During cold phases, tornado outbreaks have typically occurred in a zone stretching from southeastern Texas northeastward into Illinois, Indiana, and Michigan. During anomalously warm phases activity was mainly limited to the Gulf Coast states, including central Florida. The data are statistically and synoptically analyzed to show that they are not only statistically significant, but also meteorologically reasonable.
Goldilocks Loses Her Paradigm
Authors: Dennard Linda F.
Published: August 2008

The ongoing conversation among the public management and public administration is given a slightly more complex twist in this sequel to the story of Goldilocks and paradigms first published in Administration & Society in 1989.
Homeopathic pathogenetic trials produce more specific than non-specific symptoms: results from two double-blind placebo controlled trials
Authors: Walach H. , Möllinger H. , Sherr J. , Schneider R.
Published: August 2008

We conducted two parallel, blinded homeopathic pathogenetic trials conducted at two different sites to determine whether symptoms reported by healthy volunteers were significantly different for homeopathic remedies than for placebos. Study 1 used a two-armed design, testing ozone against placebo. Study 2 used a three-armed design, testing ozone and iridium against placebo. We found significantly more remedy-specific symptoms in provers taking ozone or iridium than in provers taking placebo in the three-armed trial and in both trials pooled for ozone and placebo. We, therefore, conclude that homeopathic remedies produce more symptoms typical for a remedy than non-typical symptoms. The results furthermore suggest a somewhat non-classical pattern because symptoms of one remedy appear to be mimicked in the other trial arm. This might be indicative of entanglement in homeopathic systems.
Health-promoting behaviours in conservatoire students
Authors: Kreutz Gunter , Ginsborg Jane , Williamon Aaron
Published: August 2008

This study focuses on health-promoting behaviours in students from two conservatoires, the Royal Northern College of Music (RNCM, Manchester, UK; n =199) and the Royal College of Music (RCM, London, UK; n = 74). The research questions concern (a) the levels and types of health-promoting behaviours among performance students and (b) the association of health-promoting behaviours with emotional state, perceived general self-regulation and self-efficacy. To address these questions, the students were surveyed using server-based inventories over the internet. Results revealed varying levels of adherence to individual aspects of health-promoting behaviours. No significant differences between the populations of the two conservatoires with respect to health-promoting behaviours were observed. In general, values for health responsibility, physical activity and stress management were lower than values for nutrition, interpersonal relations and spiritual growth. Significant correlations were found between all subscales of health-promoting behaviours, emotional state, self-efficacy and self-regulation. These results suggest that music performance students tend to focus more strongly on psychosocial than physical aspects of health while particularly neglecting health responsibility. It is also concluded that health-promoting behaviours are weakly and differentially associated with both positive and negative emotional states, as well as with perceived self-efficacy and self-regulation.
Musically untrained college students' interpretations of musical notation: sound, silence, loudness, duration, and temporal order
Authors: Tan Siu-Lan , Wakefield Elizabeth M. , Jeffries Paul W.
Published: August 2008

Fifty participants who had never learned how to read music completed a questionnaire about their interpretations of standard western musical notation. Some common assumptions were that a note must consist of a circle plus a line, symbols with unfilled spaces denote silence, the value of notes and rests increases with the size and number of features of a symbol, pitch is denoted by both note-head and stem, and tempo is determined by horizontal spacing. These assumptions are not consistent with the conventions of standard musical notation, thus the findings of the study suggest that many fundamental aspects of notation are not intuitive to beginners. Implications of the findings are discussed with respect to music pedagogy.
Results of Arthroscopic Iliopsoas Tendon Release in Competitive and Recreational Athletes
Authors: Anderson Scott A. , Keene James S.
Published: August 2008

Background

An arthroscopic iliopsoas tendon release will alleviate painful snapping of the tendon. One question that remains is whether athletes can return to sports after this procedure. This study presents the results of 5 competitive and 10 recreational athletes who had an arthroscopic release of their iliopsoas tendon.

Hypothesis

Athletes can return to full participation in their sport after an arthroscopic iliopsoas tendon release.

Study Design

Case series; Level of evidence, 4.

Methods

Fifteen athletes (2 college, 3 high school, 10 recreational) with painful snapping hips and no pain relief after anesthetic magnetic resonance arthrography had an ultrasound evaluation of their iliopsoas tendon and an anesthetic injection into the Psoas bursa. In all 15 patients, the injection relieved their hip pain, and in 10 patients, real-time imaging demonstrated snapping of the tendon. All hips were assessed with Byrd's 100-point hip scoring system before the release and at 1.5,3,6, and 12 months after surgery.

Results

Preoperative hip scores averaged 41 and 44 points for the competitive and recreational athletes, respectively. After surgery, the 2 groups used crutches for 4 weeks, and had 6-week scores that averaged 87 and 63 points. At 6 months, their scores averaged 94 and 98 points, and at 12 months, 96 and 97 points, and none had recurrence of their snapping or pain. All 15 athletes returned to full participation in their sport at an average of 9 months after surgery.

Conclusion

A return to college, high school, and recreational sports can be expected after an arthroscopic release of the iliopsoas tendon.
Biological Properties of Crosslinked Salmon Collagen Fibrillar Gel as a Scaffold for Human Umbilical Vein Endothelial Cells
Authors: Nagai Nobuhiro , Mori Kazuo , Munekata Masanobu
Published: August 2008

Collagen derived from chum salmon (Oncorhynchus keta) was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) during collagen fibrillogenesis and applied to an in vitro cell culture to evaluate its potential use as a scaffold for vascular tissue engineering. Human umbilical vein endothelial cells (HUVEC) were cultured on the crosslinked salmon collagen fibrillar gel (EDC-SC gel), and their growth rates and production levels of cytokines, including platelet-derived growth factor-BB and von Willebrand factor, were measured. Comparison was also made with bovine collagen gel crosslinked with EDC (EDC-BC gel). The growth and cytokine production of the HUVEC cultured on the EDC-SC gel were higher than those on the EDC-BC gel. In addition, HUVEC were found to attach to the EDC-BC gel through α2β1 integrin for native collagen, whereas they attached to the EDC-SC gel through αvβ3 integrin for denatured collagen as well as the α2β1 integrin, indicating that HUVEC recognized denatured domains in the EDC-SC gel. In conclusion, the EDC-SC gel can be used as a scaffold to support HUVEC growth, although the integrin-mediated attachment manner differs between the two gels.
Bovine Bone Screws: Metrology and Effects of Chemical Processing and Ethylene Oxide Sterilization on Bone Surface and Mechanical Properties
Authors: Haje D.P. , Volpon J.B. , Moro C.A.
Published: August 2008

We assess the effects of chemical processing, ethylene oxide sterilization, and threading on bone surface and mechanical properties of bovine undecalcified bone screws. In addition, we evaluate the possibility of manufacturing bone screws with predefined dimensions. Scanning electronic microscopic images show that chemical processing and ethylene oxide treatment causes collagen fiber amalgamation on the bone surface. Processed screws hold higher ultimate loads under bending and torsion than the in natura bone group, with no change in pull-out strength between groups. Threading significantly reduces deformation and bone strength under torsion. Metrological data demonstrate the possibility of manufacturing bone screws with standardized dimensions.
Modulation of Gene Expression of Rabbit Chondrocytes by Dynamic Compression in Polyurethane Scaffolds with Collagen Gel Encapsulation
Authors: Wang Peng-Yuan , Chow Hsiang-Hong , Tsai Wei-Bor , Fang Hsu-Wei
Published: August 2008

Chondrocytes have been demonstrated to be sensitive to mechanical stimuli, such as compression, tension, shear force, and hydrostatic pressure. The responses of chondrocytes to mechanical compression have been often studied in vitro with cartilage and chondrocyte/hydrogel systems. The aim of this study was to investigate the effects of dynamic compression on gene expression of rabbit chondrocytes which were seeded in elastic polyurethane scaffolds with or without collagen gel encapsulation. Dynamic compression of 20% or 30% strain with 0.1 Hz frequency was applied to the cell-seeded scaffolds for 4, 8, 12, or 24 h, and then the expression of the three genes related to chondrogenic phenotype, type I and II collagens and aggrecan, was analyzed by RT-PCR. We also investigated the gene expression of the compressed chondrocytes, which had experienced 12-h 30% strain dynamic loading, during the post-compression resting period. We found that the expression of type II collagen did not seem to respond to cyclic compression. On the other hand, aggrecan gene was stimulated by dynamic compression. The stimulatory effect disappeared gradually after the dynamic compression was ceased. Furthermore, the mechano-response of the chondrocytes to aggrecan expression was delayed by collagen gel encapsulation. The expression of type I collagen was enhanced by collagen gel. We found that collagen gel encapsulation prolonged the expression of aggrecan and type I collagen during post-compression resting period. We demonstrated that mechanical and biochemical stimuli modulate the gene expression of chondrocytes.
Sameness and Difference
Authors: Dhanda Amita
Published: August 2008

Whether one should ‘mainstream’ or adopt ‘special measures’ has been a perennial dilemma whilst devising strategies to deal with gender discrimination. The United Nations Convention on Rights of Persons with Disabilities has tried to skirt this conundrum by adopting a ‘twin track’ approach. Consequently, it has inducted the gender question in all relevant spaces, in addition to incorporating a separate article on women with disabilities. This article explores how the Convention came to adopt this approach, and what kind of interpretational and implementation efforts will be required for its promise to be realised for women with disabilities. With the acceptance of this approach, the Convention has unequivocally conceded that multiple forms and levels of discrimination require a multiplicity of rights.
Prenatal Diagnosis
Authors: Ghai Anita , Johri Rachana
Published: August 2008

Feminists in India have been concerned about the declining sex ratio in the country. The Prenatal Diagnostic Techniques (Regulation and Prevention of Misuse) Act 1994 or PNDT Act, which outlaws sex-selective abortions, has been welcomed by feminists, even though they remain concerned with bottlenecks in its implementation. A relatively unnoticed but critical issue, however, is the possibly unwitting legitimisation of the abortion of potentially disabled children. This article endeavours to question the ideology that regards abortion as the only option when prenatal testing reveals a birth abnormality, an option sanctioned by the PNDT Act. We contend that disability is, to a great extent, socially constructed: its conceptualisation reflects societal attitudes that view the lives of disabled people as tragic, worthless and a burden. The article recognises the tension between the feminist and disability activists around the issue of women's choice. These issues are discussed through the voices of the mothers of both non-disabled and disabled children in Delhi. We contend that: (a) the concept of individual choice, which is reified through the PNDT Act, is socially constructed and contextually located, and (b) while a pro-choice perspective is important to feminists, the thoughtless use of prenatal testing could reduce, rather than expand, women's choices.
Burden of Caring
Authors: Chakravarti Upali
Published: August 2008

While most parents adapt well to caring for a disabled child, some do not. The literature on disability, narratives of parents, professionals and disabled activists in India highlight the role of prevailing social conditions in the suffering of the disabled and their families. Many issues germane to their day-to-day lives are made invisible by society, and personal and social suffering are ignored. Families also require a range of support services to be able to successfully care for a disabled member. Using the case study approach, this article examines the experiences of caregiving in families of young people with cerebral palsy. It highlights the individual and social dimensions of disability, and their intersection in the lives of individuals with disabilities and their families.
The Inner World of Adolescent Girls with Hearing Impairment
Authors: Limaye Sandhya
Published: August 2008

This article explores how young females with hearing impairment respond to the developmental tasks of adolescence. Using a case study approach, the author explores Radha and Hasina's understanding and attitudes towards issues such as bodily changes, peer relationships, autonomy, economic independence, marriage and family, and personal identity. The limitations imposed by the impairment, combined with the environment to which they are exposed, may not be conducive to normal development. So, while on the one hand adolescents with hearing impairment face the same developmental needs and tasks that confront hearing adolescents, yet their passage through normal developmental stages may become more complicated. This is because the basic deprivation due to deafness is not just the sensory one of sound, but also the acquisition of communication skills. Nonetheless, instead of submitting meekly to their disability and the authority of their families, both Radha and Hasina emerge as self-assertive, individualistic and high-spirited persons who contest popular negative stereotypes of persons with disabilities. The article does not claim that the ideas contained in the two accounts are in any way representative of and equally applicable to all deaf adolescents. It is only an exploratory study, an attempt to throw light on the impact of deafness on the developmental tasks of adolescents with hearing impairment.
Once Upon a Time There Was an Organization
Authors: Baruch Yehuda
Published: August 2008

Comparing and contrasting fairy tales with organizational stories reveals that the two have very few elements in common. Nevertheless, this article shows how scholars can learn a lot from the differences and even from the absolute contrast between these two types of stories. Basically, organizational stories are antitheses of fairy tales. Fairy tales reside in the imagination realm, directed at child development and rooted in spiritual origins. Organizational stories are physical, directed at managers, based on facts, and subject to criticism. Fairy tales were developed with the passing of generations. Organizational stories either happen in the present or reflect the recent past. However, scholars can learn from both for the future, and there are certain comparable themes in both.
Krishna Basin Development
Authors: Venot Jean-Philippe , Sharma Bharat R. , Rao K.V.G.K.
Published: August 2008

Since India gained Independence, the Krishna basin has seen an increasing mobilization of its water resources. Warnings of basin closure (minimal flow to the ocean) emerge during dry periods. Basin water development and local rural dynamics have led to a degradation of downstream ecosystems manifesting itself by salinizing soil and groundwater, increasing pollution, making mangroves disappear, and desiccating wetlands. Reversing this evolution requires the formal recognition of the environment as a water user in its own right and the implementation of an environmental water provision. This provision should be based on a two-tier allocation system with assured discharges in the irrigation canals of the delta and to the ocean. This will lead to further commitment of water resources, but this is needed to reconcile the social, economic, and environmental objectives of sustainable development. Other measures facilitating integrated natural resources management from the local to the basin level are needed too.
Antisociality, Sexual Deviance, and Sexual Reoffending in Juvenile Sex Offenders
Authors: McCann Kristie , Lussier Patrick
Published: August 2008

A meta-analysis was conducted to analyze recidivism rates and assess the role of antisociality and sexual deviancy in sexual reoffending in juvenile sex offenders. The importance of these constructs is discussed with regard to current theory and in light of methodological and conceptual limitations of previous studies.
Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura
Authors: Neunert Cindy E. , Buchanan George R. , Imbach Paul , Bolton-Maggs Paula H. B. , Bennett Carolyn M. , Neufeld Ellis J. , Vesely Sara K. , Adix Leah , Blanchette Victor S. , Kühne Thomas
Published: August 2008

Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm3 and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes.
Characterization of glycolytic enzyme interactions with murine erythrocyte membranes in wild-type and membrane protein knockout mice
Authors: Campanella M. Estela , Chu Haiyan , Wandersee Nancy J. , Peters Luanne L. , Mohandas Narla , Gilligan Diana M. , Low Philip S.
Published: August 2008

Previous research has shown that glycolytic enzymes (GEs) exist as multienzyme complexes on the inner surface of human erythrocyte membranes. Because GE binding sites have been mapped to sequences on the membrane protein, band 3, that are not conserved in other mammalian homologs, the question arose whether GEs can organize into complexes on other mammalian erythrocyte membranes. To address this, murine erythrocytes were stained with antibodies to glyceraldehyde-3-phosphate dehydrogenase, aldolase, phosphofructokinase, lactate dehydrogenase, and pyruvate kinase and analyzed by confocal microscopy. GEs were found to localize to the membrane in oxygenated erythrocytes but redistributed to the cytoplasm upon deoxygenation, as seen in human erythrocytes. To identify membrane proteins involved in GE assembly, erythrocytes from mice lacking each of the major erythrocyte membrane proteins were examined for GE localization. GEs from band 3 knockout mice were not membrane associated but distributed throughout the cytoplasm, regardless of erythrocyte oxygenation state. In contrast, erythrocytes from mice lacking α-spectrin, ankyrin, protein 4.2, protein 4.1, β-adducin, or dematin headpiece exhibited GEs bound to the membrane. These data suggest that oxygenation-dependent assembly of GEs on the membrane could be a general phenomenon of mammalian erythrocytes and that stability of these interactions depends primarily on band 3.
Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion
Authors: Chizzolini Carlo , Chicheportiche Rachel , Alvarez Montserrat , de Rham Casimir , Roux-Lombard Pascale , Ferrari-Lacraz Sylvie , Dayer Jean-Michel
Published: August 2008

Microenvironment molecular cues direct T helper (Th) cell differentiation; however, Th17 fate determination is still imprecisely understood in humans. To assess the role of prostaglandin E2 (PGE2) in Th expansion, we activated peripheral blood mononuclear cells by CD3 cross-linking. In the presence of exogenous PGE2, peripheral blood mononuclear cells produced higher interleukin-17 (IL-17), C-C chemokine ligand 20 (CCL20)/macrophage inflammatory protein 3α (MIP-3α), CXC chemokine ligand 8 (CXCL8)/IL-8, and lower interferon-γ and IL-22 levels than in control cultures. Exogenous PGE2 and IL-23 synergized in inducing IL-17, whereas indomethacin and IL-23 blockade drastically reduced IL-17 but not interferon-γ production. Furthermore, IL-1 but not tumor necrosis factor was absolutely required for IL-17 production. PGE2 doubled the frequency of CD4+ T cells producing IL-17 and within the CD4+ subset enhanced C-C chemokine receptor 6 (CCR6) and CCR4 while decreasing CXC chemokine receptor 3 (CXCR3) expression. Furthermore, in CD4+ T-cell lines, the production of IL-17 segregated with the CCR6+ subset. In the presence of CCR6+ compared with CXCR3+ Th cells, monocytes/macrophages produced much higher levels of matrix metalloproteinase-1, -3, and -9 but similar levels of CXCL10 and IL-1β. These results identify PGE2 and IL-23 as participating in the expansion of CD4+ T cells endowed with high IL-17 production capacity, which in turn favors monocyte production of mediators important for host defense and tissue destruction.
Newly identified patterns of Pax2 expression in the developing mouse forebrain
Authors: Fotaki Vassiliki , Price David J , Mason John O
Published: August 2008

Background

The availability of specific markers expressed in different regions of the developing nervous system provides a useful tool for the study of mouse mutants. One such marker, the transcription factor Pax2, is expressed at the midbrain-hindbrain boundary and in the cerebellum, spinal cord, retina, optic stalk, and optic chiasm. We recently described a group of diencephalic cells that express Pax2 as early as embryonic day (E) 10.5, and become part of the eminentia thalami by E11.5. The discovery of this previously undescribed cell population prompted us to examine Pax2 protein expression in the developing mouse forebrain in more detail.

Results

We determined the expression pattern of Pax2 in the forebrain of wild type mouse embryos between E10.5 and postnatal day (P) 15. Pax2 expression was detected in the septum of the basal forebrain, hypothalamus, eminentia thalami and in the subfornical organ. To evaluate Pax2 as a marker for septal cells, we examined Pax2 expression in Pax6Sey/Seymutants, which have an enlarged septum. We found that Pax2 clearly marks a population of septal cells equivalent to that seen in wild types, indicating its utility as a marker of septal identity. These cells did not express the GABAergic marker calbindin nor the cholinergic marker choline acetyltransferase and were not detectable after P15.

Conclusion

Pax2 is expressed in populations of cells within the developing septum, hypothalamus, and eminentia thalami. It seems especially useful as a marker of the telencephalic septum, because of its early, strong and characteristic expression in this structure. Further, its expression is maintained in the enlarged septum of Pax6Sey/Seymutants.
CCL5 regulation of mucosal chlamydial immunity and infection
Authors: Sakthivel Senthilkumar K , Singh Udai P , Singh Shailesh , Taub Dennis D , Igietseme Joseph U , Lillard James W
Published: August 2008

Background

Following genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance ofChlamydia. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity againstChlamydia.

Results

The present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa followingChlamydia muriduramchallenge. Antibody (Ab)-mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1 > Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4+T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.

Conclusion

The suppression of these responses correlated with delayed clearance ofC. muriduram, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.
Lymphotoxin-alpha polymorphisms and presence of cancer in 1,536 consecutive autopsy cases
Authors: Takei Kako , Ikeda Shinobu , Arai Tomio , Tanaka Noriko , Muramatsu Masaaki , Sawabe Motoji
Published: August 2008

Background

Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine with anti-tumor activity. The objective of this study was to determine whetherLTApolymorphisms influence the presence of cancer.

Methods

LTApolymorphisms C804A (rs1041981, T60N) and T495C (rs2229094, C13R) were determined in 1,536 consecutive autopsy cases and were registered in the Japanese single-nucleotide polymorphisms (SNPs) for geriatric research (JG-SNP) Internet database. Tumors were systematically reviewed, pathologically confirmed, and assessed in relation toLTAgenotype.

Results

The study population consisted of 827 males and 709 females, with a mean age of 80 years. Altogether, we studied 606 subjects without cancer and 930 subjects with cancer of the stomach (n = 183), lung (n = 164), colon or rectum (n = 143), or other sites. The presence of cancer was higher in males than in females. The C804A and T495C polymorphisms were associated with cancer in males (CA + AA: CC, adjusted OR = 0.72, 95% CI = 0.53 – 0.99; TC + CC: TT, adjusted OR = 1.45, 95% CI = 1.04 – 2.02; respectively) but not in females. In males, the C804A polymorphism was associated with lung cancer (CA + AA: CC, adjusted OR = 0.60, 95% CI = 0.37 – 0.97), whereas the T495C polymorphism was associated with gastric cancer (TC + CC: TT, adjusted OR = 1.68, 95% CI = 1.06 – 2.65).

Conclusion

We found some evidence of an association betweenLTApolymorphisms and cancer risk in elderly Japanese men. Further studies in larger populations should examine this hypothesis.
Cost effectiveness of chest pain unit care in the NHS
Authors: Oluboyede Yemi , Goodacre Steve , Wailoo Allan ,   the ESCAPE Research Team
Published: August 2008

Background

Acute chest pain is responsible for approximately 700,000 patient attendances per year at emergency departments in England and Wales. A single centre study of selected patients suggested that chest pain unit (CPU) care could be less costly and more effective than routine care for these patients, although a more recent multi-centre study cast doubt on the generalisability of these findings.

Methods

Our economic evaluation involved modelling data from the ESCAPE multi-centre trial along with data from other sources to estimate the comparative costs and effects of CPU versus routine care. Cost effectiveness ratios (cost per QALY) were generated from our model.

Results

We found that CPU compared to routine care resulted in a non-significant increase in effectiveness of 0.0075 QALYs per patient and a non-significant cost decrease of £32 per patient and thus a negative incremental cost effectiveness ratio. If we are willing to pay £20,000 for an additional QALY then there is a 70% probability that CPU care will be considered cost-effective.

Conclusion

Our analysis shows that CPU care is likely to be slightly more effective and less expensive than routine care, however, these estimates are surrounded by a substantial amount of uncertainty. We cannot reliably conclude that establishing CPU care will represent a cost-effective use of health service resources given the substantial amount of investment it would require.
Excision of sympathetic ganglia and the rami communicantes with histological confirmation offers better early and late outcomes in Video assisted thoracoscopic sympathectomy
Authors: Rathinam Sridhar , Nanjaiah Prakash , Sivalingam Sivakumar , Rajesh Pala B
Published: August 2008

Background

Video-Assisted Thoracoscopic Sympathectomy (VATS) is an established minimally invasive procedure for thoracic sympathetic blockade in patients with hyperhidrosis, facial flushing and intractable angina. Various techniques using clips, diathermy and excision are used to perform sympathectomy. We present our technique of excision of the sympathetic chain with histological proof and the analysis of the early and late outcomes.

Methods

We evaluated 200 procedures in 100 consecutive patients, who underwent Video Assisted Thoracoscopic Sympathectomy by a single surgeon in our centre between September 1996 to March 2007. All patients had maximum medical therapy prior to surgery and were divided into 3 groups based on indications, Group 1(hyperhidrosis: 48 patients), Group 2 (facial flushing: 26 patients) and Group 3(intractable angina: 26 patients). The demography and severity of symptoms for each group were analysed. The endpoints were success rate, 30 day mortality, complications and patient's satisfaction.

Results

99 patients had bilateral VATS sympathectomy and 1 had unilateral sympathectomy. The conversion rate to open was 1(1%). All patients had successful removal of ganglia proven histologically with no perioperative mortality in our series. The complications included pneumothorax (5%), acute coronary syndrome (2%), transient Horner's syndrome (1%), transient paraesthesia (1%), wound infection (4%), compensatory hyperhidrosis (18%), residual flushing (3%) and wound pain (5%). There were five late deaths in the intractable angina group at a mean follow up of 36.7 months. Overall success rates of abolishing the symptoms were 96.3%, 87.5% and 95.2% for Group 1, 2 and 3 respectively.

Conclusion

Excision of the sympathetic chain with histological confirmation during VATS sympathectomy is a safe and effective method in treating hyperhidrosis, facial flushing and intractable angina with good long term results and satisfaction.
Hematemesis, a very rare presentation of solid pseudo-papillary tumors of the pancreas: a case report
Authors: Apostolidis Stylianos , Papavramidis Theodossis S , Zatagias Akis , Michalopoulos Antonis , Papadopoulos Vassilis N , Paramythiotis Daniel , Harlaftis Nick
Published: August 2008

Introduction

Solid pseudo-papillary tumors of the pancreas are rare and typically present in young female patients. They are slowly growing masses that may attain large size, and are of low malignant potential. Surgical resection is usually curative.

Case presentation

A 71-year-old woman presented to the emergency department with an episode of hematemesis but was otherwise hemodynamically stable. Emergency gastroscopy revealed a bleeding mass projecting to the duodenum. Fluid, blood and electrolyte resuscitation followed. Computed tomography revealed a small mass in the head of the pancreas. A Whipple operation was performed. Pathology revealed a solid pseudo-papillary tumor. The postoperative course of the patient was uneventful and no recurrence was present a year after the operation.

Conclusion

In our case, the most noteworthy observations concern the small size of the tumor, the age of the patient and the presenting symptom. However, pancreaticoduodenectomy in a 71-year-old woman is a major effort and should only be undertaken by centers and surgeons experienced in complex hepatobiliary surgery. Furthermore, the unique nature of this case reminds every clinician that each patient has to be considered separately and with extreme caution.
An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma
Authors: Ronchetti Domenica , Lionetti Marta , Mosca Laura , Agnelli Luca , Andronache Adrian , Fabris Sonia , Deliliers Giorgio Lambertenghi , Neri Antonino
Published: August 2008

Background

The role of microRNAs (miRNAs) in multiple myeloma (MM) has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs) and focused on transcripts whose expression varied significantly across the dataset.

Methods

miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets.

Results

We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK) whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and/or interactions with the bone marrow microenvironment.

Conclusion

Our data support the idea that intronic miRNAs and their host genes are regulated dependently, and may contribute to the understanding of their biological roles in cancer. To our knowledge, this is the first evidence of deregulated miRNA expression in MM, providing insights that may lead to the identification of new biomarkers and altered molecular pathways of the disease.
Prevalence and correlates of foot pain in a population‐based study: the North West Adelaide health study
Authors: Hill Catherine L , Gill Tiffany K , Menz Hylton B , Taylor Anne W
Published: August 2008

Background

Few population‐based studies have examined the prevalence of foot pain in the general community. The aims of this study were therefore to determine the prevalence, correlates and impact of foot pain in a population‐based sample of people aged 18 years and over living in the northwest region of Adelaide, South Australia.

Methods

The North West Adelaide Health Study is a representative longitudinal cohort study of n = 4,060 people randomly selected and recruited by telephone interview. The second stage of data collection on this cohort was undertaken between mid 2004 and early 2006. In this phase, information regarding the prevalence of musculoskeletal conditions was included. Overall, n = 3,206 participants returned to the clinic during the second visit, and as part of the assessment were asked to report whether they had pain, aching or stiffness on most days in either of their feet. Data were also collected on body mass index (BMI); major medical conditions; other joint symptoms and health‐related quality of life (the Medical Outcomes Study Short Form 36 [SF‐36]).

Results

Overall, 17.4% (95% confidence interval 16.2 – 18.8) of participants indicated that they had foot pain, aching or stiffness in either of their feet. Females, those aged 50 years and over, classified as obese and who reported knee, hip and back pain were all significantly more likely to report foot pain. Respondents with foot pain scored lower on all domains of the SF‐36 after adjustment for age, sex and BMI.

Conclusion

Foot pain affects nearly one in five of people in the community, is associated with increased age, female sex, obesity and pain in other body regions, and has a significant detrimental impact on health‐related quality of life.