bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Analysis of a Large Subtelomeric Nucleotide-Binding-Site–Leucine-Rich-Repeat Family in Two Representative Genotypes of the Major Gene Pools of Phaseolus vulgaris
Authors: Geffroy Valérie , Macadré Catherine , David Perrine , Pedrosa-Harand Andrea , Sévignac Mireille , Dauga Catherine , Langin Thierry
Published: December 2008

In common bean, the B4 disease resistance (R) gene cluster is a complex cluster localized at the end of linkage group (LG) B4, containing at least three R specificities to the fungus Colletotrichum lindemuthianum. To investigate the evolution of this R cluster since the divergence of Andean and Mesoamerican gene pools, DNA sequences were characterized from two representative genotypes of the two major gene pools of common bean (BAT93: Mesoamerican; JaloEEP558: Andean). Sequences encoding 29 B4-CC nucleotide-binding-site–leucine-rich-repeat (B4-CNL) genes were determined—12 from JaloEEP558 and 17 from BAT93. Although sequence exchange events were identified, phylogenetic analyses revealed that they were not frequent enough to lead to homogenization of B4-CNL sequences within a haplotype. Genetic mapping based on pulsed-field gel electrophoresis separation confirmed that the B4-CNL family is a large family specific to one end of LG B4 and is present at two distinct blocks separated by 26 cM. Fluorescent in situ hybridization on meiotic pachytene chromosomes revealed that two B4-CNL blocks are located in the subtelomeric region of the short arm of chromosome 4 on both sides of a heterochromatic block (knob), suggesting that this peculiar genomic environment may favor the proliferation of a large R gene cluster.
Statistical Mechanics and the Evolution of Polygenic Quantitative Traits
Authors: Barton N H , de Vladar H P
Published: December 2008

The evolution of quantitative characters depends on the frequencies of the alleles involved, yet these frequencies cannot usually be measured. Previous groups have proposed an approximation to the dynamics of quantitative traits, based on an analogy with statistical mechanics. We present a modified version of that approach, which makes the analogy more precise and applies quite generally to describe the evolution of allele frequencies. We calculate explicitly how the macroscopic quantities (i.e., quantities that depend on the quantitative trait) depend on evolutionary forces, in a way that is independent of the microscopic details. We first show that the stationary distribution of allele frequencies under drift, selection, and mutation maximizes a certain measure of entropy, subject to constraints on the expectation of observable quantities. We then approximate the dynamical changes in these expectations, assuming that the distribution of allele frequencies always maximizes entropy, conditional on the expected values. When applied to directional selection on an additive trait, this gives a very good approximation to the evolution of the trait mean and the genetic variance, when the number of mutations per generation is sufficiently high (4Nμ > 1). We show how the method can be modified for small mutation rates (4Nμ → 0). We outline how this method describes epistatic interactions as, for example, with stabilizing selection.
Report of Colloquium I: The Future of Pediatric Health Care Delivery and Education—Pondering Imponderables to Create an Ideal Residency in a World of Critical Uncertainties
Authors: Lister George , Murdock-Vlautin Theresa C. , Friedman Aaron L.
Published: December 2008

Participants of the first colloquium of the Residency Review and Redesign in Pediatrics (R3P) Project considered possible scenarios affecting pediatric practice over the next 15 to 20 years and speculated about the knowledge and skills that pediatricians would need to care for children, adolescents, and young adults in the future. They concluded that the imponderables and complexity of that undertaking fell into the category of a “wicked problem” with no unique solutions. The specifics of the future cannot be predicted, but the themes important to thinking about the future are clear and must be incorporated into thinking about pediatric residency education.
Pediatric Fellows: Perspectives on Training and Future Scope of Practice
Authors: Freed Gary L. , Dunham Kelly M. , Switalski Kara E. , Jones M. Douglas , McGuinness Gail A. ,   and the Research Advisory Committee of the American Board of Pediatrics
Published: December 2008

OBJECTIVE. Training for pediatric residents who intend to pursue fellowship differs little from training for residents who intend to practice general pediatrics. It is unknown how well residents who intend to pursue subspecialty training believe that residency prepares them for subspecialty fellowships or future careers. To characterize the strengths and weaknesses of residency training and the factors influencing subspecialty choice from the perspective of subspecialty fellows, we conducted a survey of current fellows on these issues.

METHODS. A random sample of 1000 physicians who were entering their second or third year of fellowship in the United States in 2007 received a structured questionnaire by mail. The survey focused on decision-making in selection of residency and fellowship programs, strength of residency training in preparation for fellowship, and plans for future practice.

RESULTS. The overall response rate was 81%. A majority of the fellows would not have shortened their general pediatrics residency before fellowship if given the option (64% [n = 482]). However, more than half (52% [n = 390]) of the fellows would have chosen a 2-year fellowship without research or scholarly activity over the current 3-year structure. Few current fellows believed they could have used any additional training in the areas of patient safety, coordination of care for children with complex illnesses, or patient communication.

CONCLUSIONS. The finding that a large proportion of fellows would opt for shortened subspecialty training should prompt discussion and debate within the profession regarding the skills necessary for a pediatric subspecialist. Patient safety, physician-parent communication, and care coordination are emphasized primarily through informal training during residency. Although most clinicians believe themselves to be adequately prepared, research has identified gaps in clinician skills and understanding of these issues of great importance to patients and their families.
Alliance for Pediatric Quality: Creating a Community of Practice to Improve Health Care for America's Children
Authors: Miles Paul V. , Miller Marlene , Payne Donna M. , Perelman Robert , Saffer Mimi , Zimmerman Edward ,   for the Alliance for Pediatric Quality
Published: December 2008

On any given day, hundreds of physicians, nurses, informaticists, health information management directors, and other health care providers are collaborating on how to improve health information technology systems for use in child health care. Many work in small communities of practice to share ideas, to find solutions, and to build innovations that support the goal of making electronic health record systems accessible by 2014. Together, they are a formidable virtual community aligned around a common strategy, to ensure that health information technology works for children. Each member in the community represents a children's hospital or pediatric practice affiliated with one of the 4 major national pediatric organizations that constitute the Alliance for Pediatric Quality. The alliance works with the pediatric health information technology community to speed the adoption of pediatric data standards and to define data collection and reporting systems that would work for both quality improvement and electronic health record systems. With this foundation, hospitals and physicians should be better positioned to improve the quality of health care for US children by implementing technology equipped to care for children, actively participating in improvement initiatives, conducting meaningful measurement of care, and appropriately reporting for accountability.
Influence of Pay-for-Performance Programs on Information Technology Use Among Child Health Providers: The Devil Is in the Details
Authors: Menachemi Nir , Struchen-Shellhorn Wendy , Brooks Robert G. , Simpson Lisa
Published: December 2008

OBJECTIVE. Pay-for-performance programs are used to promote improved health care quality, often through increased use of health information technology. However, little is known about whether pay-for-performance programs influence the adoption of health information technology, especially among child health providers. This study explored how various pay-for-performance compensation methods are related to health information technology use.

METHODS. Survey data from 1014 child health providers practicing in Florida were analyzed by using univariate and multivariate techniques. Questions asked about the adoption of electronic health records and personal digital assistants, as well as types of activities that affected child health provider compensation or income.

RESULTS. The most common reported method to affect respondents' compensation was traditional productivity or billing (78%). Of the pay-for-performance-related methods of compensation, child health providers indicated that measures of clinical care (41%), patient surveys and experience (34%), the use of health information technology (29%), and quality bonuses or incentives (27%) were a major or minor factor in their compensation. In multivariate logistic regression analyses, only pay-for-performance programs that compensated directly for health information technology use were associated with an increased likelihood of electronic health record system adoption. Pay-for-performance programs linking measures of clinical quality to compensation were positively associated with personal digital assistant use among child health providers.

CONCLUSIONS. Pay-for-performance programs that do not directly emphasize health information technology use do not influence the adoption of electronic health records among Florida physicians treating children. Understanding how different pay-for-performance compensation methods incentivize health information technology adoption is important for improving quality.
Health Information Systems and Physician Quality: Role of the American Board of Pediatrics Maintenance of Certification in Improving Children's Health Care
Authors: Miles Paul
Published: December 2008

A second revolution in quality is occurring in US health care, as profound as the Flexner revolution almost 100 years ago. Systems issues are the basis for most of the concern, but physician quality and professional development are also important. Specialty board certification and maintenance of certification are key drivers of professional development and improvement of care. Physicians are now required to document that they can assess and improve quality of care. Functional health information systems are essential for this process.
Health Information Law in the Context of Minors
Authors: Rosenbaum Sara , Abramson Susan , MacTaggart Patricia
Published: December 2008

This article presents a legal overview of privacy and autonomy considerations related to children in the context of health information technology adoption and use. All uses of health-related technologies take place within a legal framework that guides health care generally; the privacy laws and autonomy principles long predate health information technology and can be expected to shape its design and use. Furthermore, it is a legal tenet that technology advances shape the law, and this can be expected as health information technology use evolves. Most laws related to health care, medical practice, and the right to privacy are state-based and subject to high variability. As the health information revolution increasingly eliminates the importance of geographic boundaries to health care, interstate tensions can be expected to grow. Health information privacy law is even more complex in the case of children, because the relationship between privacy law and children is itself complex. The law considers minor children to be deserving of special protection against harm and risk exposure, and this concern extends to privacy. Regardless of whether minors can shield health information from parents, it is clear that parents and children have the power to control the flow of information to and among entities. Although information protections may pose a higher standard where information about children is concerned, this fact should not overshadow the extent to which information can be used under existing legal principles. Over time, as the security and safety of information sharing are established, the law may yet evolve to permit a freer flow of information.
Advancing Patient-Centered Pediatric Care Through Health Information Exchange: Update From the American Health Information Community Personalized Health Care Workgroup
Authors: Brinner Kristin A. , Downing Gregory J.
Published: December 2008

The Personalized Health Care Workgroup of the American Health Information Community was formed to foster a broad, community-based approach to facilitate the incorporation of interoperable, clinically useful, genetic/genomic information and analytical tools into electronic health records, to support clinical decision-making. The Personalized Health Care Workgroup has developed a series of use cases that outline the informational needs of multiple stakeholders (eg, patients, clinicians, organizations, and systems) and describe the information systems necessary to connect these stakeholders at multiple levels. These use case scenarios offer a guide for standardized data elements and architecture that enable interoperability (content sharing) among different formats of patient electronic health records.
The Public Role in Promoting Child Health Information Technology
Authors: Conway Patrick H. , White P. Jonathan , Clancy Carolyn
Published: December 2008

The public sector plays an important role in promoting child health information technology. Public sector support is essential in 5 main aspects of child health information technology, namely, data standards, pediatric functions in health information systems, privacy policies, research and implementation funding, and incentives for technology adoption. Some innovations in health information technology for adult populations can be transferred to or adapted for children, but there also are unique needs in the pediatric population. Development of health information technology that addresses children's needs and effective adoption of that technology are critical for US children to receive care of the highest possible quality in the future.
B-Cell Depletion for Autoimmune Thrombocytopenia and Autoimmune Hemolytic Anemia in Pediatric Systemic Lupus Erythematosus
Authors: Kumar Sathish , Benseler Susanne M. , Kirby-Allen Melanie , Silverman Earl D.
Published: December 2008

OBJECTIVES. Our goal was to determine long-term efficacy and safety of B-cell–depletion therapy for children with autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus.

PATIENTS AND METHODS. A retrospective, single-center cohort study was conducted including all patients with pediatric systemic lupus erythematosus who were diagnosed with autoimmune thrombocytopenia and/or autoimmune hemolytic anemia and treated with rituximab. Treatment efficacy and safety parameters were monitored and recorded.

RESULTS. Nine patients with pediatric systemic lupus erythematosus were included in the study: 5 had autoimmune thrombocytopenia, 3 had autoimmune hemolytic anemia, and 1 had both. There were 5 female and 4 male patients; median age at diagnosis of pediatric systemic lupus erythematosus was 14 years (range: 8–16 years); and median pediatric systemic lupus erythematosus disease duration to time of rituximab treatment was 6 months (range: 2–30 months). Complete response was achieved in all 6 children with autoimmune thrombocytopenia (median time to complete response: 2 weeks [range: 1–12 weeks]). Two patients' conditions flared at 48 and 68 weeks, respectively, and were re-treated. The remaining 4 patients continued to be in remission at 24, 32, 36, and 88 weeks, respectively. All 4 children with autoimmune hemolytic anemia achieved complete response at a median time of 4 weeks (range: 4–32 weeks). All patients remained in complete response at 24, 44, 84, and 100 weeks of follow-up. Complete B-cell depletion was seen in all children after rituximab treatment. No serious infections occurred, but 1 patient had an infusion reaction.

CONCLUSIONS. Preliminary evidence suggests that B-cell–depletion therapy with rituximab is an efficacious and safe treatment for autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus. Despite the prolonged effect on B-cell numbers and function, no serious infections were observed.
Regression of progestin-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors in Sprague–Dawley rats by p53 reactivation and induction of massive apoptosis: a pilot study
Authors: Benakanakere Indira , Besch-Williford Cynthia , Ellersieck Mark R , Hyder Salman M
Published: December 2008

p53 Reactivation and induction of massive apoptosis (PRIMA-1) is a small-molecule compound that reactivates mutant p53, restoring its normal tumor suppressor function. PRIMA-1 effectively suppresses the growth of homogeneous p53-deficient tumor xenografts in immunosuppressed mice; however, the ability of PRIMA-1 to suppress the growth of mammary tumors in rodents and other species is not well characterized. Here, we examined the ability of PRIMA-1 to suppress the growth of 7,12-dimethylbenz[a]anthracene (DMBA)-induced and progestin-accelerated DMBA-induced mammary tumors in Sprague–Dawley rats. Mammary tumors were induced in female rats with DMBA or DMBA plus progestin treatment. After tumors had reached 5–25 mm2 in size, PRIMA-1 was administered twice a day for 3 days via tail vein injection (20 or 50 mg/kg). Tumor size was monitored every day following PRIMA-1 for at least 15 days prior to killing. PRIMA-1 caused regression of ∼40% of progestin-accelerated DMBA-induced mammary tumors, but did not induce regression of native non-progestin-accelerated DMBA-induced tumors. Importantly, PRIMA-1 also suppressed the emergence of any new progestin-accelerated tumors in this model. Immunological studies with an antibody that selectively reacts with mutant p53 suggested that none of the native DMBA-induced tumors expressed mutant p53. By contrast, six out of eight progestin-accelerated DMBA-induced tumors stained for mutant p53 protein. In PRIMA-1-treated tumor-bearing rats, tumor regression correlated with conversion of mutant to wild-type p53 conformation, reduced expression of vascular endothelial growth factor and estrogen receptor, lack of blood vessel perfusion, increased expression of p21, and massively increased expression of anti-angiogenic protein, secreted protein acidic and rich in cysteine. These pre-clinical results suggest that PRIMA-1, as a single agent or in combination with other anti-cancer compounds, has potential as a novel chemotherapeutic treatment for progestin-accelerated human breast cancer.
Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats
Authors: Samuelson Emma , Hedberg Carola , Nilsson Staffan , Behboudi Afrouz
Published: December 2008

Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS, and CTNNB1 (β-Catenin) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (Cadherin 1 or E-Cadherin) expression. However, many human EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1, and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.
Temperature Rise Within the Pulp Chamber During Composite Resin Polymerisation Using Three Different Light Sources
Authors: Santini A , Watterson C , Miletic V
Published: December 2008

The purpose of the study was to compare temperature rise during polymerisation of resin based composites

(RBCs) with two LED light curing units (LCUs) compared to a halogen control light.

Methods:

Forty-five extracted molars, patients aging 11-18 years were used. Thermocouples (TCs) were placed in contact with the roof of the pulp chamber using a ‘split-tooth’ method. Teeth were placed in a water bath with the temperature of the pulp chamber regulated at 37°±1°C.

Group 1 (control):

Prismatics® Lite II (Dentsply Detrey, Konstanz, Germany), a halogen LCU, light intensity 500 mW/cm2.

Group 2:

Bluephase® ( Ivoclar Vivadent, Schaan, Liechtenstein), light intensity 1100 mW/cm2. Group 3:Elipar Freelight2 (3M ESPE, Seefeld, Germany), light intensity 1000 mW/cm2. Temperature changes were continuously recorded with a data logger connected to a PC.

Results:

Significantly higher temperature rise was recorded during bond curing than RBC curing in all 3 groups. (Halogen; p =0.0003: Bluephase; p=0.0043: Elipar; p=0.0002.). Higher temperatures were recorded during polymerisation of both Bond and RBC with both LED sources than with the halogen control. There was no significant difference between the two LED,LCUs (Bond:p=0.0279: RBC p=0.0562: Mann-Whitney).

Conclusion:

The potential risk of pulpal injury during RBC polymerisation is increased when using light-curing units with high energy output compared to low energy output light sources. The rise is greatest when curing bonding agent alone and clinicians are advised to be aware of the potential hazard of thermal trauma to the pulp when using high intensity light sources. However the mean temperature rise with all three units was below the limits normally associated with permanent pulp damage.
Aberrant Cytoplasmic Accumulation of Connexin 43 in Human Testicular Seminoma
Authors: Mauro V. , Chevallier D. , Gilleron J. , Defamie N. , Carette D. , Gasc J.M. , Segretain D. , Pointis G.
Published: December 2008

In the present study Cx43 mRNA and protein were analyzed in germ cells of men with normal spermatogenesis
and in human testicular seminoma. In normal testis Cx43 mRNAs were basally located within seminiferous tubules and
expressed in the most basally located germ cells (spermatogonia, early spermatocytes, and pachytene spermatocytes) and
in Sertoli cells. Immunofluorescence analysis showed that Cx43 signal was mainly located in the basal compartment of
seminiferous tubules and was stage-dependent. Cx43 mRNAs were also detected in human testicular seminoma.
Transcripts were present within seminoma cells identified by PLAP staining. However, Cx43 protein exhibited an
intracytoplasmic accumulation, within an intracellular compartment distinct from the Golgi apparatus and was
undetectable at the plasma membrane level, suggesting post-translational rather than transcriptional abnormalities. This
aberrant intracytoplasmic accumulation of Cx43 is due neither to a dysfunction of the protein trafficking machinery nor to
a specific alteration of its major protein partner, ZO-1, since the tight junction associated protein was detected at the
plasma membrane level and did not colocalize with Cx43.
Novel Risk Factors for Atherosclerosis
Authors: Papazafiropoulou Athanasia , Katsilambros Nicholas , Tentolouris Nicholas
Published: December 2008

Epidemiologic studies demonstrated that the classical cardiovascular risk factors explain only a part of the increased
cardiovascular morbidity and mortality. Large scale studies have shown that novel cardiovascular risk factors, including
increased plasma homocysteine, fibrinogen, C-reactive protein, uric acid levels, and increased white blood cells
count as well as low adiponectin levels, might have a key role in the pathogenesis of the cardiovascular disease. This review
examines recent literature data on the effect of novel risk factors on cardiovascular morbidity and mortality in
healthy subjects as well as in subjects at high cardiovascular risk. In addition, the pathogenetic mechanisms linking the effects
of the novel risk factors with atherosclerosis are discussed.
Teacher Efficacy in Rural Zimbabwe
Authors: Dunham Judy K. , Song'Ony Daniel
Published: December 2008

The need to address contextual variables, such as cultural bias and cultural norms, is a common challenge for researchers in international education. This article highlights societal conditions and cultural issues that could have impacted teacher efficacy data in Zimbabwe, a country known for its ongoing economic crisis, political repression, and societal instability. In light of the country's circumstances, it is likely that Zimbabwean teachers' efficacy (i.e. their self-confidence in their ability to produce positive student outcomes) is diminished. The 23 educators in this study were from nine impoverished rural schools where there are few opportunities for professional growth. During July of 2006, they completed the 24-item Ohio State Teacher Efficacy Scale (OSTES) at the beginning of a professional development workshop. The data were analysed to ascertain whether these educators had faith in their abilities to expect good results from their efforts. The results of this study suggest that the teachers possessed high levels of teacher efficacy. These results are interpreted in light of potential cultural differences in the construct of teacher efficacy.
C-Reactive Protein and 5-Year Survival in Type 2 Diabetes
Authors: Bruno Graziella , Fornengo Paolo , Novelli Giulia , Panero Francesco , Perotto Massimo , Segre Olivia , Zucco Chiara , Deambrogio PierCarlo , Bargero Giuseppe , Perin Paolo Cavallo
Published: December 2008

OBJECTIVE

To determine to what extent plasma C-reactive protein (CRP) values influence 5-year all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of albumin excretion rate (AER) and other cardiovascular risk factors, and its incremental usefulness for predicting individual risk of mortality.

RESEARCH DESIGN AND METHODS

Measurements of CRP were performed in 2,381 of 3,249 (73.3%) subjects as part of the population-based Casale Monferrato Study. Its association with 5-year all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. The C statistic and measures of calibration and global fit were also assessed.

RESULTS

Results are based on 496 deaths in 11.717 person-years of observations (median follow-up 5.4 years). With respect to subjects with CRP ≤3 mg/l, those with higher values had an adjusted hazard ratio (HR) of 1.51 (95% CI 1.18–1.92) for all-cause mortality and 1.44 (0.99–2.08) for cardiovascular mortality. In normoalbuminuric subjects, respective HRs of CRP were 1.56 (1.13–2.15) and 1.65 (1.00–2.74), AER being neither a modifier nor a confounder of CRP association. In analysis limited to diabetic subjects without cardiovascular disease (CVD), adjusted HRs were 1.67 (1.24–2.24) for all-cause mortality and 1.36 (0.83–2.24) for cardiovascular mortality. The improvement in individual risk assessment was marginal when measured with various statistical measures of model discrimination, calibration, and global fit.

CONCLUSIONS

CRP measurement is independently associated with short-term mortality risk in type 2 diabetic individuals, even in normoalbuminuric subjects and in those without a previous diagnosis of CVD. Its clinical usefulness in individual assessment of 5-year risk of mortality, however, is limited.
Angiotensin II Reduces Mitochondrial Content in Skeletal Muscle and Affects Glycemic Control
Authors: Mitsuishi Masanori , Miyashita Kazutoshi , Muraki Ayako , Itoh Hiroshi
Published: December 2008

OBJECTIVE—Blockade of angiotensin (Ang) II has been shown to prevent new-onset type 2 diabetes. We focused on the effects of AngII on muscle mitochondria, especially on their biogenesis, as an underlining mechanism of type 2 diabetes.

RESEARCH DESIGN AND METHODS—C2C12 cells and C57bl/6 mice were used to examine roles for AngII in the regulation of muscle mitochondria and to explore whether the effect was mediated by type 1 AngII receptor (AT1R) or type 2 receptor (AT2R).

RESULTS—C2C12 cells treated with 10−8–10−6 mol/l AngII reduced the mitochondrial content associated with downregulation of the genes involved in mitochondrial biogenesis. The action of AngII was diminished by blockade of AT2R but not AT1R, whereas overexpression of AT2R augmented the effect. AngII increased mitochondrial ROS and decreased mitochondrial membrane potential, and these effects of AngII were significantly suppressed by blockade of either AT1R or AT2R. Chronic AngII infusion in mice also reduced muscle mitochondrial content in association with increased intramuscular triglyceride and deteriorated glycemic control. The AngII-induced reduction in muscle mitochondria in mice was partially, but significantly, reversed by blockade of either AT1R or AT2R, associated with increased fat oxidation, decreased muscle triglyceride, and improved glucose tolerance. Genes involved in mitochondrial biogenesis were decreased via AT2R but not AT1R under these in vivo conditions.

CONCLUSIONS—Taken together, these findings imply the novel roles for AngII in the regulation of muscle mitochondria and lipid metabolism. AngII reduces mitochondrial content possibly through AT1R-dependent augmentation of their degradation and AT2R-dependent direct suppression of their biogenesis.
Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes
Authors: Putnam Amy L. , Brusko Todd M. , Lee Michael R. , Liu Weihong , Szot Gregory L. , Ghosh Taumoha , Atkinson Mark A. , Bluestone Jeffrey A.
Published: December 2008

OBJECTIVE—Regulatory T-cells (Tregs) have catalyzed the field of immune regulation. However, translating Treg-based therapies from animal models of autoimmunity to human clinical trials requires robust methods for the isolation and expansion of these cells—a need forming the basis for these studies.

RESEARCH DESIGN AND METHODS—Tregs from recent-onset type 1 diabetic patients and healthy control subjects were isolated by fluorescence-activated cell sorting and compared for their capacity to expand in vitro in response to anti-CD3–anti-CD28–coated microbeads and IL-2. Expanded cells were examined for suppressive function, lineage markers and FOXP3, and cytokine production.

RESULTS—Both CD4+CD127lo/− and CD4+CD127lo/−CD25+ T-cells could be expanded and used as Tregs. However, expansion of CD4+CD127lo/− cells required the addition of rapamycin to maintain lineage purity. In contrast, expansion of CD4+CD127lo/−CD25+ T-cells, especially the CD45RA+ subset, resulted in high yield, functional Tregs that maintained higher FOXP3 expression in the absence of rapamycin. Tregs from type 1 diabetic patients and control subjects expanded similarly and were equally capable of suppressing T-cell proliferation. Regulatory cytokines were produced by Tregs after culture; however, a portion of FOXP3+ cells were capable of producing interferon (IFN)-γ after reactivation. IFN-γ production was observed from both CD45RO+ and CD45RA+ Treg populations.

CONCLUSIONS—The results support the feasibility of isolating Tregs for in vitro expansion. Based on expansion capacity, FOXP3 stability, and functional properties, the CD4+CD127lo/−CD25+ T-cells represent a viable cell population for cellular therapy in this autoimmune disease.
Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study
Authors: Hivert Marie-France , Manning Alisa K. , McAteer Jarred B. , Dupuis Josée , Fox Caroline S. , Cupples L. Adrienne , Meigs James B. , Florez Jose C.
Published: December 2008

OBJECTIVE— The RETN gene encodes the adipokine resistin. Associations of RETN with plasma resistin levels, type 2 diabetes, and related metabolic traits have been inconsistent. Using comprehensive linkage disequilibrium mapping, we genotyped tag single nucleotide polymorphisms (SNPs) in RETN and tested associations with plasma resistin levels, risk of diabetes, and glycemic traits.

RESEARCH DESIGN AND METHODS— We examined 2,531 Framingham Offspring Study participants for resistin levels, glycemic phenotypes, and incident diabetes over 28 years of follow-up. We genotyped 21 tag SNPs that capture common (minor allele frequency >0.05) or previously reported SNPs at r2 > 0.8 across RETN and its flanking regions. We used sex- and age-adjusted linear mixed-effects models (with/without BMI adjustment) to test additive associations of SNPs with traits, adjusted Cox proportional hazards models accounting for relatedness for incident diabetes, and generated empirical P values (Pe) to control for type 1 error.

RESULTS— Four tag SNPs (rs1477341, rs4804765, rs1423096, and rs10401670) on the 3′ side of RETN were strongly associated with resistin levels (all minor alleles associated with higher levels, Pe<0.05 after multiple testing correction). rs10401670 was also associated with fasting plasma glucose (Pe = 0.02, BMI adjusted) and mean glucose over follow-up (Pe = 0.01; BMI adjusted). No significant association was observed for adiposity traits. On meta-analysis, the previously reported association of SNP −420C/G (rs1862513) with resistin levels remained significant (P = 0.0009) but with high heterogeneity across studies (P < 0.0001).

CONCLUSIONS— SNPs in the 3′ region of RETN are associated with resistin levels, and one of them is also associated with glucose levels, although replication is needed.
Physical Activity and the Metabolic Syndrome in Elderly German Men and Women
Authors: Hahn Valerie , Halle Martin , Schmidt-Trucksäss A. , Rathmann W. , Meisinger C. , Mielck A.
Published: December 2008

OBJECTIVE—The purpose of this study is to determine the optimal duration and intensity of exercise for elderly people for the prevention of the metabolic syndrome.

RESEARCH DESIGN AND METHODS—The population-based Cooperative Research in the Region of Augsburg (KORA) S4 Survey with 1,653 participants aged 55–74 years was used to investigate the relationship between the metabolic syndrome and physical activity.

RESULTS—Fifty-seven percent of men and 48% of women showed clinical symptoms of the metabolic syndrome. Leisure activities were common (>80% walked >30 min/day). Sports activities performed regularly for ≤1 h per week reduced the odds of having the metabolic syndrome (odds ratio 0.70 [95% CI 0.49–1.02] for men and 0.74 [0.53–1.04] for women), and sports activities >2 h per week were even more effective (0.62 [0.42–0.92] for men and 0.59 [0.39–0.89] for women). In contrast, activities such as walking and cycling did not have an additional influence.

CONCLUSIONS—Intense physical activity by the elderly should be promoted in addition to leisure physical activity for the prevention of the metabolic syndrome.
Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy
Authors: Krishnan Singhan T.M. , Quattrini Cristian , Jeziorska Maria , Malik Rayaz A. , Rayman Gerry
Published: December 2008

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD).

RESEARCH DESIGN AND METHODS—Fifteen healthy control subjects, 10 subjects with type 2 diabetes and painful neuropathy (PFN), and 12 subjects with type 2 diabetes and painless neuropathy (PLN) were studied. LDIflare and QST were performed on the dorsum of the foot, and dermal NFD was determined.

RESULTS—Results of both large- and small-fiber quantitative sensory tests were abnormal in patients with PLN but not those with PFN compared with control subjects. Dermal NFD was also significantly reduced in the PLN group compared with control subjects (205.8 ± 165.3 vs. 424.9 ± 176.3 [mean ± SD]; P = 0.003) but not in the PFN group (307.6 ± 164.5). In contrast, the LDIflare (square centimeters) was reduced in both PFN (1.59 ± 0.41) and PLN (1.51 ± 0.56) groups compared with control subjects (4.38 ± 1.4) (P < 0.001 for both). NFD correlated significantly with the LDIflare (r = 0.57, P < 0.0001).

CONCLUSIONS—The LDIflare demonstrated impaired small-fiber function in patients with PFN when other assessments revealed no abnormality. We believe that this method has potential diagnostic value, particularly because it is noninvasive, has excellent reproducibility, and correlates with NFD. Furthermore, it may have an important role in assessing preventative therapies in early neuropathy.
Aggressive Pediatric Meningioma with Soft Tissue and Lymph Node Metastases: A Case Report
Authors: Doxtader Erika E. , Butts Sydney C. , Holsapple James W. , Fuller Christine E.
Published: December 2008

Metastatic meningioma is extremely rare, occurring in an estimated 0.1% of cases. We report a case of pediatric meningioma metastatic to cervical soft tissue and lymph nodes. An 8-year-old boy presented with headaches, dizziness, and involuntary eye flickering. Magnetic resonance imaging (MRI) revealed a 7.5-cm parasagittal, dural-based mass with venous sinus encasement. Therapeutic embolization was followed by bilateral craniotomy, achieving subtotal resection. Histopathologic examination revealed an atypical meningioma with regions of hypercellularity, small cell morphology, sheeting architecture, increased mitoses, and brain invasion. Surveillance MRI studies showed growth of residual tumor and enlarging cervical soft tissue masses with posterior triangle lymphadenopathy. Radiation and surgical resection were employed for the intracranial tumor burden; resection of the soft tissue masses revealed metastatic meningioma, with soft tissue infiltration and metastasis to 8 lymph nodes. This case demonstrates the aggressive biologic potential of pediatric meningiomas, with potential for distant spread via cerebrospinal fluid leakage and lymphatic invasion.
NMDA-induced stimulation of glycolysis in developing hippocampal cell cultures
Authors: Luengviriya Jiraporn , Helmeke Carina , Braun Katharina , Hauser Marcus , Mair Thomas
Published: December 2008

Developmental changes in energy metabolism of primary hippocampal cell cultures from newborn rats were investigated during the first 3 weeks. These changes were measured by intensity of and number of cells exhibiting NAD(P)H fluorescence in response to NMDA-induced activation of neuronal activity. We observed gradual changes of stimulation-evoked NAD(P)H signaling over the first 3 weeks, such that at day 7 and 16, this stimulation is minimal, while at 5 and 12 days, it is maximal. These results describe a biphasic pattern that was similar to earlier findings from experiments investigating developmental changes in population spike amplitudes or glutamate release in young rats. Inhibition of mitochondrial respiration by KCN revealed that the NMDA-evoked stimulation of energy metabolism is mainly due to increased glycolytic activity.
Properties of Concrete Containing Vitreous Calcium Aluminosilicate Pozzolan
Authors: Hossain Akhter B. , Shirazi Satiar A. , Persun Jarrod , Neithalath Narayanan
Published: December 2008

A laboratory study was done on the influence of vitreous calcium aluminosilicate (VCAS), a new pozzolanic mineral admixture, on the properties of fresh and hardened portland cement concrete. A relative comparison was done of the performance of concrete containing VCAS with that of concrete containing silica fume (SF), one of the widely used mineral admixtures. The addition of VCAS pozzolan increased the slump (improved consistency) of the mixtures, while the addition of SF decreased it. The VCAS pozzolan was found not to have significant influence on the plastic shrinkage cracking potential of the mixtures while SF increased it. The compressive strength development of both the VCAS and SF mixtures was found to be higher than that of the control mixture. The experimental results showed that both VCAS and SF increased the free shrinkage of concrete. The rapid chloride permeability (RCP) values for mixtures with VCAS and SF specimens were significantly lower than those of the control concrete. At equal replacements of cement with either VCAS or SF, the reduction in RCP values was higher for the SF modified mixtures. Incorporation of either VCAS or SF also reduced the sorptivity and moisture diffusion coefficient of the concrete mixtures. This study provides insight into the behavior of concretes containing two high-performance mineral admixtures.
Influence of Curing Conditions on Strength Development and Strength Predictive Capability of Maturity Method
Authors: Radlinski Mateusz , Olek Jan , Nantung Tommy
Published: December 2008

Applicability of the maturity method to ternary systems with fly ash (FA) and silica fume (SF) has been investigated through laboratory and field studies. The laboratory study explored the impact of the combined effect of initial curing conditions and mixture composition on the compressive strength development and strength predictive capability of the maturity method. It was demonstrated that the maturity method can be used effectively to predict compressive strength of ternary concrete containing ordinary portland cement, FA, and SF. However, the accuracy of this method was strongly influenced by the amount of moisture supplied during early stages of curing and to a lesser extent by relative amounts of FA and SF in the mixture. Further (intermittent) moist curing of field trial batch (FTB) concrete (potentially simulating natural precipitation) was found to have a beneficial effect on strength development and, consequently, on the accuracy of strength prediction using the maturity method. Thus, even an occasional supply of moisture to high-performance concrete (especially at early age) may significantly minimize potential strength losses. Finally, applicability of the maturity method to ternary bridge deck concrete made and placed under field conditions and exposed to ambient temperature variations was verified. The predicted strength of bridge deck concrete was found to be approximately 10 MPa lower than the actual strength, irrespective of age. However, a correction factor was established to account for different air content in field concrete (compared with FTB concrete that was used for development of maturity function), which resulted in much more accurate strength estimates.
Mapping the Domain of Medical Informatics
Authors: Talmon J. L. , Moorman P. W. , Kors J. A. , Schuemie M. J.
Published: December 2008

Objectives: The domain of medical informatics (MI) is not well defined. It covers a wide range of research topics. Our objective is to characterize the field of MI by means of the scientific literature in this domain.

Methods: We used titles and abstracts from MEDLINE records of papers published between July 1993 and July 2008, and extracted uni-, bi- and trigrams as features. Starting with the ISI category of medical informatics, we applied a semi-automated procedure to identify the set of journals and proceedings pertaining to MI. A clustering algorithm was subsequently applied to the articles from this set of publications.

Results: MI literature can be divided into three subdomains: 1) the organization, application, and evaluation of health information systems, 2) medical knowledge representation, and 3) signal and data analysis. Over the last fifteen years, the field has remained relatively stable, although most journals have shifted their focus somewhat.

Conclusions: We identified the scientific literature pertaining to the field of MI, and the main areas of research. We were able to show trends in the field, and the positioning of different journals within this field.
Future Developments of Medical Informatics from the Viewpoint of Networked Clinical Research
Authors: Kuchinke W. , Ohmann C.
Published: December 2008

Objectives: To be prepared for future developments, such as enabling support of rapid innovation transfer and personalized medicine concepts, interoperability of basic research, clinical research and medical care is essential. It is the objective of our paper to give an overview of developments, indicate problem areas and to specify future requirements.

Methods: In this paper recent and ongoing large-scaled activities related to interoper-ability and integration of networked clinical research are described and evaluated. The following main topics are covered: necessity for general IT-conception, open source/open community approach, acceptance of eSource in clinical research, interoperability of the electronic health record and electronic data capture and harmonization and bridging of standards for technical and semantic inter-operability.

Results: National infrastructures and programmes have been set up to provide general IT-conceptions to guide planning and development of software tools (e.g. TMF, ca BIG, NIHR). The concept of open research described by transparency achieved through open access, open data, open communication and open source software is becoming more and more important in clinical research infrastructure development (e.g. ca BIG, ePCRN). Meanwhile visions and rules for using eSource in clinical research are available, with the potential to improve interoperability between the electronic health record and electronic data capture (e.g. CDISC e SDI, eClinical Forum/PhRMA EDC/eSource Taskforce). Several groups have formulated user requirements, use cases and technical frameworks to advance these issues (e.g. NHIN Slipstream-project, EHR/CR-project, IHE). In order to achieve technical and semantic interoperability, existing standards (e.g. CDISC) have to be harmonized and bridged. Major consortia have been formed to provide semantical inter-operability (e.g. HL7 RCRIM under joint leadership of HL7, CDISC and FDA, or BRIDG covering CDISC, HL7, FDA, NCI) and to provide core sets of data collection fields (CDASH).

Conclusions: The essential tasks for medical informatics within the next ten years will now be the development and implementation of encompassing IT conceptions, strong support of the open community and open source approach, the acceptance of eSource in clinical research, the uncompromising continuity of standardization and bridging of technical standards and the widespread use of electronic health record systems.