bluuebunny/crossref_metadata_2025 huggingface dataset:
Retórica y poética en la evolución de los géneros poéticos cuatrocentista
Authors: Gmóez-Bravo Ana M.
Published: February 2007

Abstract: El cambio en la relación entre poesía y música y en las formas de lectura acaecido a finales de la Edad Media lleva a reconsiderar las distinciones comúnmente aceptadas para géneros cancioneriles cuatrocentistas tan representativos como los de la canción y el decir. La elucidación de la naturaleza de estos géneros debe comprender una apreciación comprehensiva de sus orígenes y carácter retóricos, así como dar cuenta cumplida de su evolución. Esta evolución, junto con la relación de las dos denominaciones de género se explica a través de los cambios ocurridos en la teoría poética y retórica de finales de la Edad Media y su relación con el incipiente humanismo.
Ciceronian Rhetoric in Italy, 1260-1350
Authors: Cox Virginia
Published: February 2007

Abstract: The later thirteenth and early fourteenth centuries in Italy saw a marked new interest in the study of Ciceronian rhetorical theory, in both Latin and vernacular contexts. This reflects the increasing prominence within the civic culture of the Italian communes of practices of oral and adversarial rhetoric which the dominant instrument of rhetorical instruction in this period, the ars dictaminis, was ill-equipped to teach. While the utility of the strategies of argument taught by Roman rhetorical theory was widely recognised in this period, the ethical attitudes implicit in that theory represented a challenge to prevailing Christian constructions of the moral decorum of speech. Classical rhetorical theory may thus be seen to have constituted a destabilising presence within late medieval ethical discourse: a situation which presisted, to some extent, even after the political and cultural changes of the later Trecento had displaced rhetoric in Italy from a primary to a secondary, literary and educational, role.
The Intended Public of Demetrius's On Style: The Place of the Treatise in the Hellenistic Educational System
Authors: Schenkeveld Dirk M.
Published: February 2007

Abstract: On Style, written by a certain Demetrius probably in the first century B.C., is an important witness to the rhetorical education of the third/second centuries B.C. It is a matter of long scholarly debate whether Demetrius intended his treatise to be a handbook of rhetoric or a work of literary criticism. Here it is argued that the public Demetrius writes his book for are pupils who have done the preliminary courses in rhetoric and have leamt to write progymnasmata. They now enter the final course on rhetoric and will compose the more difficult exercises, commonly termed declamationes.
Beowulf's “ane ben” and the Rhetorical Context of the “Hunferþ Episode”
Authors: Church A. P.
Published: February 2007

Abstract: Recent scholarship argues that Anglo-Saxon rhetorical strategies derive from an extended grammatical curriculum such as the praeexercitamina, an argument which complements the trend to rehabilitate our understanding of the Anglo-Saxons, from the romantic notion that they were bound to native conventions to one which recognizes their acquisition and application of Latin learning. This paper extends these arguments by seeking to show that elements of the progymnasmata, on which the praeexercitamina are based, seem to inform the invention and arrangement of material in the “Hunfer]) Episode” of Beowulf.
An in situ electrical measurement technique via a conducting diamond tip for nanoindentation in silicon
Authors: Ruffell S. , Bradby J.E. , Williams J.S. , Warren O.L.
Published: March 2007

An in situ electrical measurement technique for the investigation of nanoindentation using a Hysitron Triboindenter is described, together with details of experiments to address some technical issues associated with the technique. Pressure-induced phase transformations in silicon during indentation are of particular interest but are not fully understood. The current in situ electrical characterization method makes use of differences in electrical properties of the phase-transformed silicon to better understand the sequence of transformations that occur during loading and unloading. Here, electric current is measured through the sample/indenter tip during indentation, with a fixed or variable voltage applied to the sample. This method allows both current monitoring during indentation and the extraction of current-voltage (I-V) characteristics at various stages of loading. The work presented here focuses on experimental issues that must be understood for a full interpretation of results from nanoindentation experiments in silicon. The tip/sample contact and subsurface electrical resistivity changes dominate the resultant current measurement. Extracting the component of contact resistance provides an extremely sensitive method for measuring the electrical properties of the material immediately below the indenter tip, with initial results from indentation in silicon showing that this is a very sensitive probe of subsurface structural and electrical changes.
Backwater Immigration by Fishes through a Water Control Structure: Implications for Connectivity and Restoration
Authors: Schultz Douglas W. , Garvey James E. , Brooks Ronald C.
Published: March 2007

Recent efforts to reduce sediment loading in large-river backwaters have relied on inexpensive low-maintenance structures that promote river–backwater connectivity. How these structures influence ichthyofauna is not understood. We quantified the distribution of fishes through a stop-log structure installed during the Swan Lake habitat restoration project on the lower Illinois River. Modified hoop nets were systematically fished simultaneously in a two-dimensional 3 vertical × 3 horizontal grid of net locations to capture fish as they immigrated into the lake through the structure. Catches were dominated by gizzard shad Dorosoma cepedianum and freshwater drum Aplodinotus grunniens. Adult freshwater drum, adult common carp Cyprinus carpio, and juvenile silver carp Hypophthalmichthys molitrix exhibited an affinity for the lower two-thirds of the water column. Lengths of freshwater drum increased with depth, particularly during the spring. Common carp catch rates were highest during spring, whereas those for silver carp were highest during fall and winter. Closure of the bottom two-thirds of the lower Swan Lake water control structure could reduce immigration of exotic and undesirable species into the backwater; their recruitment associated with the lake could be affected accordingly. The water control structure does not appear to have negatively affected lateral fish movement. However, habitat quality and availability probably determine seasonal patterns in backwater use. In systems where exotic species are abundant, lateral connectivity may need to be assessed from a cost-benefit perspective, specifically as it pertains to maintaining habitat availability for indigenous fishes versus limiting habitat availability for introduced species.
Biomechanical Effects of Rapid Palatal Expansion on the Craniofacial Skeleton with Cleft Palate: A Three-Dimensional Finite Element Analysis
Authors: Pan Xiaogang , Qian Yufen , Yu Jia , Wang Dongmei , Tang Yousheng , Shen Gang
Published: March 2007

Objective:

To explore the biomechanical effects of rapid palatal expansion (RPE) on the craniofacial skeleton with cleft palate.

Design:

A finite element model of a patient's skull with cleft lip and palate (CLP) was generated using data from spiral computed tomographic (CT) scans. Finite elemental analysis (FEA) was performed to depict the physiological changes and stress distribution in craniofacial structures loaded with orthopedic forces that created 5 mm of displacement on the region of the maxillary first premolar and first molar crown.

Patients, participants:

A 14-year-old girl with left complete unilateral CLP was included in this study.

Interventions:

Spiral CT was carried out prior to any treatment.

Main outcome measure(s):

Three-dimensional (3D) features of displacement and stress distribution were analyzed following application of transverse orthopedic force.

Results:

Marked amount of displacement and deformation occurred in the dental region. Asymmetric displacement and deformation of UCLP under RPE were evident. The stress generated by RPE was dispersed around the cleft palate and nasal cavity, and was distributed at the buttress of the maxilla-inferior border of the nasal cavity, outboard of the orbit, and central frontal bone near the nasion.

Conclusions:

Application of RPE to UCLP patients induces a pyramid-like displacement of the nasomaxillary complex along with fan-like expansion of the upper dental arch. The uniqueness of RPE with UCLP, however, lies in the asymmetric expansion and dispersed stress distribution around the lateral maxilla buttress and outboard of orbit.
A Randomized Control Trial Investigating the Effect of Presurgical Orthopedics on Feeding in Infants with Cleft Lip and/or Palate
Authors: Masarei A. G. , Wade A. , Mars M. , Sommerlad B. C. , Sell D.
Published: March 2007

Objective:

To investigate the controversial assertion that presurgical orthopedics (PSO) facilitate feeding in infants with cleft lip and palate.

Design:

Randomized control trial of 34 infants with nonsyndromic complete unilateral cleft lip and palate and 16 with cleft of the soft and at least two thirds of the hard palate. Allocation to receive presurgical orthopedics or not used minimization for parity and gender. Other aspects of care were standardized.

Setting:

The North Thames Regional Cleft Centre.

Main Outcome Measures:

Measurements were made at 3 months of age (presurgery) and at 12 months of age (postsurgery). Primary outcomes were anthropometry and oral motor skills. Objective measures of sucking also were collected at 3 months using the Great Ormond Street Measure of Infant Feeding. Twenty-one infants also had videofluoroscopic assessment.

Results:

At 1 year, all infants had normal oral motor skills and no clear pattern of anthropometric differences emerged. For both cleft groups, infants randomized to presurgical orthopedics were, on average, shorter. The presurgical orthopedics infants were, on average, lighter in the unilateral cleft and lip palate group, but heavier in the isolated cleft palate group. Infants with complete unilateral cleft and lip palate randomized to presurgical orthopedics had lower average body mass index (mean difference PSO-No PSO: −0.45 (95% confidence interval [−1.78, 0.88]), this trend was reversed among infants with isolated cleft palates (mean difference PSO-No PSO: 1.98 [−0.95, 4.91]). None of the differences were statistically significant at either age.

Conclusions:

Presurgical orthopedics did not improve feeding efficiency or general body growth within the first year in either group of infants.
Legal Considerations in the Management of Cleft Lip and Palate
Authors: Berbert-Campos Cláudia
Published: March 2007

Objectives:

To inform professionals providing care to individuals with cleft lip and palate on the legal aspects and organizations available to protect individuals with this alteration, and to advocate that cleft lip and palate should be considered a handicap, even though it is provisional and may be rehabilitated, to assure afflicted individuals basic rights and complete personal, social, and economic welfare.

Design:

Literature review on the issue, including assessment of national and international laws, doctrines, and jurisprudences; conceptual analysis of the word “handicapped” in dictionaries. Analysis included the federal constitutions of Brazil, France, Argentina, Spain, Cuba, Italy, China, Portugal, Japan, Great Britain, and Colombia, regarding the protection of handicapped people.

Results:

Constitutional protection of handicapped people is a recent issue that has been addressed only in the last few decades in some countries such as Brazil, Italy, Spain, China, and Portugal. The Brazilian Federal Constitution of 1988 addresses the protection of handicapped people to assure them access to social and individual rights, freedom, security, welfare, development, equality, and justice as supreme values of a fraternal, pluralist, and prejudice-free society.

Conclusions:

Individuals with cleft lip and palate should be included in national policies for integration of handicapped people, in agreement with programs of human rights, establishing a collaborative action between state and society. This would assure their inclusion in the socioeconomic and cultural context and equal opportunities in society, without privileges or paternalism.
Peak strength of overconsolidated clays
Authors: Atkinson J.
Published: February 2007

The peak strength of overconsolidated clay soil is conventionally related to the effective stress by a linear Mohr–Coulomb criterion in which the parameters c′p and ϕ′p depend on the nature of the soil grains, on the water content, and on the range of stress over which measurements are made. For soils that have zero or very small interparticle bonding the failure line must pass through or close to the point τ = 0 and σ′ = 0, and it must meet the critical state line, so a linear Mohr–Coulomb criterion cannot satisfactorily describe the peak strength of soil except over relatively small ranges of effective stress. The paper reports the results of special triaxial tests in which the peak strengths of samples of stiff clays from southeast England were measured at small effective stresses and large overconsolidation ratios. For each soil the peak strength, with a suitable normalising parameter to take account of water content, was related to the effective stress by a non-linear power law criterion similar to that familiar in rock mechanics. In addition, the peak stress ratios were linked to a state parameter through a relationship similar to that for ordinary Cam clay. For each clay tested the material parameters that describe the peak strength were found to be only loosely related to their plasticity.
Community Coalitions as a System: Effects of Network Change on Adoption of Evidence-Based Substance Abuse Prevention
Authors: Valente Thomas W. , Chou Chich Ping , Pentz Mary Ann
Published: March 2007

Objectives. We examined the effect of community coalition network structure on the effectiveness of an intervention designed to accelerate the adoption of evidence-based substance abuse prevention programs.

Methods. At baseline, 24 cities were matched and randomly assigned to 3 conditions (control, satellite TV training, and training plus technical assistance). We surveyed 415 community leaders at baseline and 406 at 18-month follow-up about their attitudes and practices toward substance abuse prevention programs. Network structure was measured by asking leaders whom in their coalition they turned to for advice about prevention programs. The outcome was a scale with 4 subscales: coalition function, planning, achievement of benchmarks, and progress in prevention activities. We used multiple linear regression and path analysis to test hypotheses.

Results. Intervention had a significant effect on decreasing the density of coalition networks. The change in density subsequently increased adoption of evidence-based practices.

Conclusions. Optimal community network structures for the adoption of public health programs are unknown, but it should not be assumed that increasing network density or centralization are appropriate goals. Lower-density networks may be more efficient for organizing evidence-based prevention programs in communities.
Assessing the Status of Partnerships Between Academic Institutions and Public Health Agencies
Authors: Livingood William C. , Goldhagen Jeffrey , Little William L. , Gornto Jennifer , Hou Tao
Published: March 2007

We identified, described, and defined models of academic institution–public health agency partnerships in Florida. The study involved a mixed-method research design using data collected from a survey of 67 county health department (CHD) administrators and directors in Florida, in-depth interviews of key informants, and reviews of relevant Florida statutes and other archival data providing context for the partnerships.

Fifty-one of the CHDs (76%) participated in the survey. Most reported formal agreements involving 50 different academic institutions. The partnerships were perceived to enhance the local public health system’s capacity. Recommendations focus on the need for a multitiered system for recognition of the partnerships and expansion of federal support for partnership beyond existing approaches.
Who’s In and Who’s Out: Use of Primary Medical Care Among People Living With HIV
Authors: Meyerson Beth E. , Klinkenberg W. Dean , Perkins Donna R. , Laffoon Benjamin T.
Published: March 2007

Objectives. We sought to achieve a more comprehensive picture of access to medical care for the treatment of HIV (HIV primary care) by combining evidence of medical services used (health utilization) and epidemiological client-level data.

Methods. This study integrated health information from several data sources to measure utilization of HIV primary care in the St Louis, Mo, area between 1998 and 2002. Data from disparate HIV health utilization databases were combined with data from the Missouri HIV and AIDS Reporting System database and then deidentified to measure client-level utilization of HIV primary care over time.

Results. About half of those with HIV showed evidence of having utilized HIV primary care in a given year. Although most of this group utilized HIV primary care in the first year after they received their HIV diagnosis, evidence of subsequent utilization was inconsistent. Utilization of primary care was most strongly associated with an AIDS diagnosis. About one quarter of people diagnosed with HIV after 1997 had an AIDS diagnosis when they first tested positive for HIV.

Conclusions. This study was the first of its kind to integrate several databases to understand HIV primary health care utilization over a period of years. Our findings reinforce the importance of CD4 and viral load values as indicators of utilization of HIV primary health care, particularly in the absence of other health data sets. The lack of available data and the way in which source data were available limited the study.
Sustainable Development: A Better Holistic View
Authors: Turcotte David
Published: February 2007

This article offers a critique of an article by Margrit Hugentobler that proposes a multi-systems level framework to guide sustainable development initiatives and evaluate completed projects. While praising Hugentobler's analysis of inadequacies with the United Nations' concept of sustainable development and her proposal for an integrative approach, this article raises concerns about the proposed framework's ability to equally achieve economic, environ- mental, and social objectives. As a better alternative, the author suggests a non-hierarchal, holistic framework. Moreover, this article contends that a sustainable development framework must include a focus on fair compensation and health and safety of workers.
Modeling Black‐Tailed Deer Population Dynamics Using Structured and Unstructured Approaches
Authors: GILBERT BRIAN A. , RAEDEKE KENNETH J. , SKALSKI JOHN R. , STRINGER ANGELA B.
Published: March 2007

Abstract: We used cohort analysis to reconstruct the female segment of a Columbian black‐tailed deer (Odocoileus hemionus columbianus) population from 1979 to 2000 in the western Cascades of Washington, USA. We used reconstructed population estimates and age class representations to analyze relationships between population change and female density, forage availability, and weather influences. We applied stage structured and unstructured modeling approaches and used information‐theoretic methods to select the best models. We used habitat covariates to develop predictive functions for fertility and survival parameters in structured models. The best structured and unstructured models were composed of combinations of factors including population density, forage availability, and winter weather. Structured and unstructured models could assist with management of black‐tailed deer by providing the ability to predict deer population change given covariate values.
Management Implications of Cover Selection Data: Northern Bobwhite Example
Authors: HILLER TIM L. , GUTHERY FRED S. , RYBAK ALEXANDER R. , FUHLENDORF SAMUEL D. , SMITH STEVEN G. , PUCKETT WILLIAM H. , BAKER ROBERT A.
Published: March 2007

Abstract: We derived a method of estimating the direction and magnitude of cover changes for potentially maximizing wildlife abundance on an area. We illustrate the method with data on cover selection by northern bobwhites (Colinus virginianus) collected in the Texas Panhandle from 2000 to 2003. We used radiotelemetry to determine use of cover associations, Geographic Information System analysis to determine their availability, and logic related to use‐availability analysis to collapse 95% kernel home ranges to usable space. Bobwhites selected mixed‐shrub cover consisting of sand plum (Prunus angustifolia) and fragrant sumac (Rhus aromatica), and they avoided or neutrally used 8 other cover associations. However, grass upland and sand sagebrush (Artemisia filifolia) associations occurred in ≥86% of home ranges (n = 96 bobwhites with ≥30 radiolocations). Usable space averaged 54.2% ± 1.72 SE of kernel home ranges. The data indicated that adding about 226 ha of mixed‐shrub cover or a structural homologue while simultaneously reducing the quantity of most other cover associations would maximize bobwhite abundance. An area with 30–60% mixed‐shrub cover, with the balance in grass upland and sand sagebrush, and with cover dispersed such that no point was >30 m from mixed‐shrub cover was hypothetically optimal for bobwhites in our region. Within certain constraints (e.g., financial, social, edaphic), managers can apply this method by manipulating cover types through relevant management practices (e.g., planting, prescribed burning, mechanical removal of vegetation). This method, with minor modification, could also be used to decrease usable space on an area, and thus decrease wildlife densities, should that be the manager's objective.
Habitat Use and Survival of Preflight Wild Turkey Broods
Authors: SPEARS BRIAN L. , WALLACE MARK C. , BALLARD WARREN B. , PHILLIPS RICHARD S. , HOLDSTOCK DERRICK P. , BRUNJES JOHN H. , APPLEGATE ROGER , MILLER MICHAEL S. , GIPSON PHILLIP S.
Published: March 2007

Abstract: Wild turkey (Meleagris gallopavo) broods spend the first several days of life on the ground until poult flight capabilities are attained. This is a critical period of wild turkey life history, with poult survival ranging from 12% to 52%. We measured vegetation in plots used by Rio Grande wild turkey (M. g. intermedia) preflight broods at 4 sites in southwest Kansas and the Texas Panhandle, USA, to determine microhabitat selection for ground roosting and to determine if microhabitat was related to poult survival. Hens selected ground‐roost locations with more visual obstruction from multiple observation heights than random sites. Plots surrounding ground roosts had 1) greater visual obstruction; 2) increased tree decay; 3) higher percent grass, shrub, litter, and forb cover; and 4) lower percent bare ground cover than random sites. Grass, shrubs, and downed trees appeared to provide desired cover for ground‐roosting broods. Poult survival increased with age of poult, size of brood, and density of shrubs 1–2 m tall. Plots used by broods <10 days old with above average survival contained more visual obstruction and shrubs than plots used by broods 10–16 days old with above average survival, signifying a shift in habitat use by successful broods as poults attain flight abilities. Density of shrubs 1–2 m tall in brood‐use areas appears to be important for poult survival to 16 days of age on southern Great Plains rangeland habitats. Ground‐level vegetative cover appears to be a significant factor in preflight poult survival. Provisions of ground‐level vegetative cover should be considered during wild turkey brooding periods where increased poult survival is desired.
CCL4 Protects From Type 1 Diabetes by Altering Islet β-Cell–Targeted Inflammatory Responses
Authors: Meagher Craig , Arreaza Guillermo , Peters Andrew , Strathdee Craig A. , Gilbert Philippe A. , Mi Qing-Sheng , Santamaria Pere , Dekaban Gregory A. , Delovitch Terry L.
Published: February 2007

We previously reported that interleukin (IL)-4 treatment of nonobese diabetic (NOD) mice elevates intrapancreatic CCL4 expression and protects from type 1 diabetes. Here, we show that antibody neutralization of CCL4 abrogates the ability of T-cells from IL-4–treated NOD mice to transfer protection against type 1 diabetes. Intradermal delivery of CCL4 via a plasmid vector stabilized by incorporation of the Epstein-Barr virus EBNA1/oriP episomal maintenance replicon (pHERO8100-CCL4) to NOD mice beginning at later stages of disease progression protects against type 1 diabetes. This protection was associated with a Th2-like response in the spleen and pancreas; decreased recruitment of activated CD8+ T-cells to islets, accompanied by diminished CCR5 expression on CD8+ T-cells; and regulatory T-cell activity in the draining pancreatic lymph nodes. Thus, inflammatory responses that target islet β-cells are suppressed by CCL4, which implicates the use of CCL4 therapeutically to prevent type 1 diabetes.
Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin
Authors: Harmancey Romain , Senard Jean-Michel , Rouet Philippe , Pathak Atul , Smih Fatima
Published: February 2007

We generated preadipocyte cell lines impaired in adrenomedullin production through integration of an adrenomedullin small interfering RNA expression vector. The reduction of adrenomedullin synthesis strongly accelerated adipose differentiation. These results were bolstered when overexpression of active adrenomedullin peptide led to delayed differentiation. Therefore, we propose that adrenomedullin is an antiadipogenic factor. Moreover, we checked whether insulin, a proadipogenic factor, regulates expression of adrenomedullin. We observed that insulin had an inhibitory effect on adrenomedullin expression in isolated human adipocyte cells. This response was dose dependent and was reversed by resistin, a new anti-insulin agent. We quantified circulating adrenomedullin in healthy obese patients and observed a threefold increase of adrenomedullin compared with lean patients. Furthermore, adrenomedullin plasma levels are negatively correlated to plasma insulin levels in these obese patients. The insulin inhibitory response was also observed in vivo in Sprague-Dawley rats but not in the insulin-resistant Zucker rat, suggesting that adrenomedullin expression is upregulated in insulin-resistant adipose cells. Using adrenomedullin promoter-luciferase reporter gene constructs, we have shown that the adrenomedullin response to insulin is mediated by insulin-responsive elements. These findings provide new insight into fat mass development and the relationship between obesity and elevated circulating adrenomedullin levels in diabetic patients.
Common Variation in LMNA Increases Susceptibility to Type 2 Diabetes and Associates With Elevated Fasting Glycemia and Estimates of Body Fat and Height in the General Population
Authors: Wegner Lise , Andersen Gitte , Sparsø Thomas , Grarup Niels , Glümer Charlotte , Borch-Johnsen Knut , Jørgensen Torben , Hansen Torben , Pedersen Oluf
Published: February 2007

Mutations in LMNA encoding lamin A and C proteins cause monogenic syndromes characterized by muscular dystrophy and familial partial lipodystrophy. Eight tag single nucleotide polymorphisms in the LMNA locus were genotyped in 7,495 Danish whites and related to metabolic and anthropometric traits. The minor T-allele of rs4641 was nominally associated with type 2 diabetes (odds ratio 1.14 [95% CI 1.03–1.26], P = 0.01) in a study of 1,324 type 2 diabetic patients and 4,386 glucose-tolerant subjects and with elevated fasting plasma glucose levels in a population-based study of 5,395 middle-aged individuals (P = 0.008). The minor T-allele of rs955383 showed nominal association with obesity in a study of 5,693 treatment-naïve subjects (1.25 [1.07–1.64], P = 0.01), and after dichotomization of waist circumference, the minor alleles of rs955383 and rs11578696 were nominally associated with increased waist circumference (1.14 [1.04–1.23], P = 0.003; 1.12 [1.00–1.25], P = 0.04). The minor G-allele of rs577492 was associated with elevated fasting serum cholesterol and short stature (P = 3.0 · 10−5 and P = 7.0 · 10−4). The findings are not corrected for multiple comparisons and are by nature exploratory. However, if replicated, these findings suggest that less severe variation in a gene locus known to harbor severe mutations causing monogenic syndromes may modestly increase susceptibility to common metabolic and anthropometrical phenotypes of polygenic origin.
In Mice With Type 2 Diabetes, a Vascular Endothelial Growth Factor (VEGF)-Activating Transcription Factor Modulates VEGF Signaling and Induces Therapeutic Angiogenesis After Hindlimb Ischemia
Authors: Li Yongjun , Hazarika Surovi , Xie Donghua , Pippen Anne M. , Kontos Christopher D. , Annex Brian H.
Published: February 2007

Peripheral arterial disease is a major complication of diabetes. The ability to promote therapeutic angiogenesis may be limited in diabetes. Type 2 diabetes was induced by high-fat feeding C57BL/6 mice (n = 60). Normal chow–fed mice (n = 20) had no diabetes. Mice underwent unilateral femoral artery ligation and excision. A plasmid DNA encoded an engineered transcription factor designed to increase vascular endothelial growth factor expression (ZFP-VEGF). On day 10 after the operation, the ischemic limbs received 125 μg ZFP-VEGF plasmid or control. Mice were killed 3, 10, or 20 days after injection (n = 10/group, at each time point). Limb blood flow was measured by laser Doppler perfusion imaging. VEGF mRNA expression was examined by real-time PCR. VEGF, Akt, and phospho-Akt protein were measured by enzyme-linked immunosorbent assay. Capillary density, proliferation, and apoptosis were assessed histologically. Compared with normal mice, mice with diabetes had greater VEGF protein, reduced phospho-Akt–to–Akt ratio before ligation, and an impaired perfusion recovery after ligation. At 3 and 10 days after injection, in mice with diabetes, gene transfer increased VEGF expression and signaling. At later time points, gene transfer resulted in better perfusion recovery. Gene transfer with ZFP-VEGF was able to promote therapeutic angiogenesis mice with type 2 diabetes.
Effects of Pioglitazone on Suppressor of Cytokine Signaling 3 Expression
Authors: Kanatani Yukiko , Usui Isao , Ishizuka Ken , Bukhari Agussalim , Fujisaka Shiho , Urakaze Masaharu , Haruta Tetsuro , Kishimoto Tadamitsu , Naka Tetsuji , Kobayashi Masashi
Published: February 2007

Pioglitazone is widely used for the treatment of diabetic patients with insulin resistance. The mechanism of pioglitazone to improve insulin sensitivity is not fully understood. Recent studies have shown that the induction of suppressor of cytokine signaling 3 (SOCS3) is related to the development of insulin resistance. Here, we examined whether the insulin-sensitizing effect of pioglitazone affects the SOCS induction. In db/db mice and high-fat–fed mice, expression of SOCS3 mRNA in fat tissue was increased compared with that in lean control mice, and pioglitazone suppressed SOCS3 levels. In 3T3-L1 adipocytes, mediators of insulin resistance such as tumor necrosis factor-α (TNF-α), interleukin-6, growth hormone, and insulin increased SOCS3 expression, which was partially inhibited by pioglitazone. The ability of pioglitazone to suppress SOCS3 induction by TNF-α was greatly augmented by peroxisome proliferator–activated receptor γ overexpression. SOCS3 overexpression and tyrphostin AG490, a Janus kinase 2 inhibitor, or dominant-negative STAT3 expression partially inhibited adiponectin secretion and was accompanied by decreased STAT3 phosphorylation. Conversely, pioglitazone increased adiponectin secretion and STAT3 phosphorylation in fat tissue of db/db mice and in 3T3-L1 adipocytes. These results suggest that pioglitazone exerts its effect to improve whole-body insulin sensitivity in part through the suppression of SOCS3, which is associated with the increase in STAT3 phosphorylation and adiponectin production in fat tissue.
Glucose Regulation of Insulin Gene Transcription and Pre-mRNA Processing in Human Islets
Authors: Evans-Molina Carmella , Garmey James C. , Ketchum Robert , Brayman Kenneth L. , Deng Shaoping , Mirmira Raghavendra G.
Published: February 2007

Glucose is the primary regulator of insulin granule release from pancreatic islets. In rodent islets, the role of glucose in the acute regulation of insulin gene transcription has remained unclear, primarily because the abundance and long half-life of insulin mRNA confounds analysis of transcription by traditional methods that measure steady-state mRNA levels. To investigate the nature of glucose-regulated insulin gene transcription in human islets, we first quantitated the abundance and half-lives of insulin mRNA and pre-mRNAs after addition of actinomycin D (to stop transcription). Our results indicated that intron 1–and intron 2–containing pre-mRNAs were ∼150- and 2,000-fold less abundant, respectively, than mature mRNA. 5′ intron 2–containing pre-mRNAs displayed half-lives of only ∼60 min, whereas all other transcripts displayed more extended lifetimes. In response to elevated glucose, pre-mRNA species increased within 60 min, whereas increases in mature mRNA did not occur until 48 h, suggesting that measurement of mature mRNA species does not accurately reflect the acute transcriptional response of the insulin gene to glucose. The acute increase in pre-mRNA species was preceded by a sixfold increase in histone H4 acetylation and a twofold increase in RNA polymerase II recruitment at the insulin promoter. Taken together, our data suggest that pre-mRNA species may be a more reliable reflection of acute changes to human insulin gene transcriptional rates and that glucose acutely enhances insulin transcription by a mechanism that enhances chromatin accessibility and leads to recruitment of basal transcriptional machinery.
The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone Activation
Authors: da-Silva Wagner S. , Harney John W. , Kim Brian W. , Li Jing , Bianco Suzy D.C. , Crescenzi Alessandra , Christoffolete Marcelo A. , Huang Stephen A. , Bianco Antonio C.
Published: February 2007

Disturbances in energy homeostasis can result in obesity and other metabolic diseases. Here we report a metabolic pathway present in normal human skeletal muscle myoblasts that is activated by the small polyphenolic molecule kaempferol (KPF). Treatment with KPF leads to an ∼30% increase in skeletal myocyte oxygen consumption. The mechanism involves a several-fold increase in cyclic AMP (cAMP) generation and protein kinase A activation, and the effect of KPF can be mimicked via treatment with dibutyryl cAMP. Microarray and real-time PCR studies identified a set of metabolically relevant genes influenced by KPF including peroxisome proliferator–activated receptor γ coactivator-1α, carnitine palmitoyl transferase-1, mitochondrial transcription factor 1, citrate synthase, and uncoupling protein-3, although KPF itself is not a direct mitochondrial uncoupler. The cAMP-responsive gene for type 2 iodothyronine deiodinase (D2), an intracellular enzyme that activates thyroid hormone (T3) for the nucleus, is approximately threefold upregulated by KPF; furthermore, the activity half-life for D2 is dramatically and selectively increased as well. The net effect is an ∼10-fold stimulation of D2 activity as measured in cell sonicates, with a concurrent increase of ∼2.6-fold in the rate of T3 production, which persists even 24 h after KPF has been removed from the system. The effects of KPF on D2 are independent of sirtuin activation and only weakly reproduced by other small polyphenolic molecules such as quercetin and fisetin. These data document a novel mechanism by which a xenobiotic-activated pathway can regulate metabolically important genes as well as thyroid hormone activation and thus may influence metabolic control in humans.
Glycemic and Risk Factor Control in Type 1 Diabetes
Authors: Eeg-Olofsson Katarina , Cederholm Jan , Nilsson Peter M. , Gudbjörnsdóttir Soffia , Eliasson Björn ,   for the Steering Committee of the Swedish National Diabetes Register
Published: February 2007

OBJECTIVE—This study was designed to investigate the clinical characteristics of a large type 1 diabetic population and to evaluate the degree of fulfillment of recently updated treatment goals.

RESEARCH DESIGN AND METHODS—The Swedish National Diabetes Register was initiated in 1996 as a tool for quality assurance in diabetes care. A1C levels, treatment, and risk factors were analyzed in two cross-sectional samples of 9,424 patients in 1997 and 13,612 patients in 2004 and in a smaller longitudinal sample from 1997 to 2004.

RESULTS—Mean A1C decreased from 8.2 ± 1.3% in 1997 to 8.0 ± 1.2% in 2004 (P < 0.001). The proportion of patients reaching A1C <7.0% increased from 17.4 to 21.2% in 2004. A slow but significant improvement in blood pressure levels was seen, but only 61.3% reached the blood pressure goal of <130/80 mmHg in 2004. Lipid control improved, and the use of lipid-lowering drugs increased. Among patients treated with lipid-lowering agents, 38% reached the goal of total cholesterol <4.5 mmol/l, and 48% reached the goal of LDL cholesterol <2.5 mmol/l. Successful long-term glycemic and blood pressure control were both independently predicted by low BMI and the absence of microalbuminuria in 1997.

CONCLUSIONS—In this large cohort of type 1 diabetic patients, there was a slow improvement in glycemic and risk factor control from 1997 to 2004, although the gap between the clinical results and current Swedish and American treatment goals is still unsatisfactory. It is crucial that additional measures be taken to improve risk factor control in type 1 diabetic patients.
NOS3 Polymorphisms Are Associated With Arterial Stiffness in Children With Type 1 Diabetes
Authors: Zineh Issam , Beitelshees Amber L. , Haller Michael J.
Published: February 2007

OBJECTIVE—Type 1 diabetes is associated with endothelial dysfunction, arterial stiffness, and an increased risk of cardiovascular disease (CVD) events. We previously demonstrated increased arterial stiffness in children with type 1 diabetes compared with control subjects. However, traditional CVD risk factors did not explain the difference in arterial stiffness. Furthermore, children with type 1 diabetes displayed notable within-group variation in arterial stiffness. We hypothesized that polymorphisms in the NOS3 gene may be associated with the differences seen in arterial stiffness within the population of children with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Thirty-six consecutively enrolled subjects aged 10–21 years with type 1 diabetes were studied. Subjects underwent radial tonometry in a fasting state. A corrected augmentation index (AI75) was the primary measure of arterial stiffness. Genotypes were determined for the NOS3 −786T→C and Glu298→Asp polymorphisms by pyrosequencing. AI75 values by genotype groups were compared by ANOVA and multivariate analysis.

RESULTS—Median (interquartile range) AI75 values for −786TT and −786C carriers were −3.5 (−8.8 to 2.3) and 11.0 (6.0 to 14.4), respectively (P = 0.01); AI75 values for Glu298Glu patients and Asp298 carriers were 2.3 (−4.0 to 13.0) and 7.3 (−2.0 to 11.5), respectively (P = 0.59). In univariate analysis, age, sex, BMI percentile, and −786T→C genotype were significantly associated with AI75. The multivariate model, which included these four variables, was significantly associated with AI75 (P = 0.002, R2 = 0.40).

CONCLUSIONS—This is the first reported association between −786T→C and arterial stiffness in type 1 diabetes. Larger studies are needed to confirm this observation for potential translation to risk assessment.
The Impact of Glycemic Control on Neonatal Outcome in Singleton Pregnancies Complicated by Gestational Diabetes
Authors: González-Quintero Víctor Hugo , Istwan Niki B. , Rhea Debbie J. , Rodriguez Lorna I. , Cotter Amanda , Carter Jena , Mueller Antoaneta , Stanziano Gary J.
Published: February 2007

OBJECTIVE—To identify the impact of suboptimal blood glucose control on neonatal outcomes in women with gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—Included were patients with singleton gestation enrolled in an outpatient GDM management program for at least 7 days who delivered at term. Blood glucose control was defined as an average fasting blood glucose of <95 mg/dl, 1-h postprandial of <140 mg/dl, or 2-h postprandial of <120 mg/dl. Data were compared between patients with optimal blood glucose control (n = 2,030) and those with suboptimal blood glucose control (n = 1,188). The primary study outcome was a composite variable consisting of macrosomia, large-for-gestational-age, hypoglycemia, jaundice, or stillbirth.

RESULTS—Over one-third of infants in the poorly controlled group were positive for at least one factor comprising the composite variable compared with 24% from the controlled group (P < 0.001).

CONCLUSIONS—Suboptimal glycemic control in women with GDM is associated with adverse neonatal outcome. Careful monitoring of blood glucose levels and initiation of appropriate treatment are essential in the care of women with GDM.
Habitual Physical Activity Is Associated With Intrahepatic Fat Content in Humans
Authors: Perseghin Gianluca , Lattuada Guido , De Cobelli Francesco , Ragogna Francesca , Ntali Georgia , Esposito Antonio , Belloni Elena , Canu Tamara , Terruzzi Ileana , Scifo Paola , Del Maschio Alessandro , Luzi Livio
Published: February 2007

OBJECTIVE—Fatty liver may be involved in the pathogenesis of type 2 diabetes. Physical exercise is a tool to improve insulin sensitivity, but little is known about its effect on intrahepatic fat (IHF) content. The purpose of this study was to examine the association of habitual physical activity, insulin resistance, and adiponectin with IHF content.

RESEARCH DESIGN AND METHODS—Participants were 191 (77 female and 114 male) apparently healthy, nonalcoholic individuals (aged 19–62 years; BMI 17.0–35.5 kg/m2). IHF content was assessed in a quantitative fashion and noninvasively as a continuous variable by means of 1H magnetic resonance spectroscopy (MRS), and habitual physical activity was assessed by means of a questionnaire. Fatty liver was defined as IHF content of >5% wet weight, and insulin sensitivity was estimated using the computer homeostasis model assessment (HOMA)-2 indexes.

RESULTS—A reduced prevalence of fatty liver in the quartile of the most physically active individuals (25, 11, 25, and 2% in quartile 1, 2, 3, and 4, respectively; χ2 = 15.63; P = 0.001) was found along with an inverse correlation between the physical activity index and the IHF content when plotted as continuous variables (Pearson’s r = −0.27; P < 0.000). This association was not attenuated when adjusted for age, sex, BMI, HOMA-2, and adiponectin (partial correlation r = −0.25; P < 0.001).

CONCLUSIONS—This study demonstrated that a higher level of habitual physical activity is associated with a lower IHF content and suggested that this relationship may be due to the effect of exercise per se.
Classification of Distinct Baseline Insulin Infusion Patterns in Children and Adolescents With Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy
Authors: Holterhus Paul-Martin , Odendahl Rainer , Oesingmann Sandra , Lepler Rudolf , Wagner Verena , Hiort Olaf , Holl Reinhard ,   the German/Austrian DPV Initiative and the German Pediatric CSII Working Group
Published: February 2007

OBJECTIVE—We hypothesized systematic differences in the patterns of programmed basal insulin infusion rates in children and adolescents with type 1 diabetes on continuous subcutaneous insulin infusion (CSII). We aimed at classification of basal insulin infusion rate regimens and comparing patients’ underlying clinical characteristics.

RESEARCH DESIGN AND METHODS—The German/Austrian diabetes data acquisition system for prospective surveillance database for quality control and scientific surveys in pediatric diabetology served as the primary data source. Latest (September 2004) basal insulin infusion rates of all 1,248 patients with type 1 diabetes on CSII (0.38–18 years) were analyzed (dataset 1). Basal insulin infusion rates per hour were expressed relative to mean basal insulin infusion rates per 24 h. Unsupervised clustering was used to classify basal insulin infusion rate patterns. Clinical characteristics of patients falling into distinct basal insulin infusion rate clusters were compared by Kruskal-Wallis test. Changes of basal insulin infusion rates in 64 patients were followed from initial settings before CSII to latest programming in an independent dataset 2.

RESULTS—Seven different basal insulin infusion rate patterns occurred in dataset 1. A dawn-dusk pattern was used in 708 patients (14.9 ± 2.4 years) with the peak basal insulin infusion rate at 5 a.m. Additional patterns showed only one basal insulin infusion rate oscillation per 24 h with a backshift of peak basal insulin infusion rates in younger children (P < 0.000001) (1 a.m.: n = 152, 12.4 years and 9 p.m.: n = 117, 8.9 years). All but two patients in dataset 2 were initially set on dawn-dusk patterns but showed a comparable diversification of basal insulin infusion rates during follow-up with backshift of peak basal insulin infusion rates in younger children (P < 0.01).

CONCLUSIONS—Pediatric diabetologists shape distinct basal insulin infusion rate profiles during treatment of CSII patients, mainly reflecting differences in age. Our data strongly suggest that age-dependent endocrine changes during childhood (e.g., puberty) affect circadian distribution of insulin needs in CSII, which should be kept in mind when considering basal insulin infusion rate strategies in children and adolescents.
Discordance in Perceptions of Barriers to Diabetes Care Between Patients and Primary Care and Secondary Care
Authors: Simmons David , Lillis Steven , Swan Judith , Haar Jarrod
Published: February 2007

OBJECTIVE—We sought to compare perceived barriers to diabetes care between people with diabetes and different health professional groups.

RESEARCH DESIGN AND METHODS—This was a cross-sectional, postal, open-questionnaire survey conducted in the Waikato district, New Zealand. A total of 3,890 individuals with diabetes participated, as well as 436 primary and secondary health professionals.

RESULTS—Barriers were reported in 69.7% of patients. Psychological barriers were most important (55.5%), followed by systems barriers (25.7%), and then knowledge as least important (15.3%). Psychological barriers were ranked first among general practitioners (91.0%), but systems barriers were ranked first by other health professionals (38.8–100%). General practitioner and patient barrier group rankings were similar (rT = 0.976, P < 0.05). Of specific barriers among individuals with diabetes, strictness of treatment regimen was the most frequently reported (42.3 vs. 0.1–16.8%) (P < 0.001) and 2.5 (95% CI 2.4–2.7)- to 3.4 (3.2–3.7)-fold more than the 2nd through 4th ranked barriers. Motivation was the most common specific barrier reported by general practitioners (86%), practice nurses (31.5%), and the diabetes team (85.7%). Practice and hospital nurse/dietitian rankings were most comparable with patients (rT = 0.457 and 0.466, respectively, both P < 0.05). A major area of patient–health professional discordance was the influence of other health problems, which was ranked 2nd among patients but 10th–18th among health professionals.

CONCLUSIONS—The most important barriers to diabetes care perceived by patients are psychological and particularly relate to the strictness of the regimen. Discordance between patients and different health professionals exists in the perception of the importance of different barriers to diabetes care.