bluuebunny/crossref_metadata_2025 huggingface dataset:
An Off-the-Shelf Instant Contact Casting Device for the Management of Diabetic Foot Ulcers
Authors: Piaggesi Alberto , Macchiarini Silvia , Rizzo Loredana , Palumbo Francesca , Tedeschi Anna , Nobili Laura Ambrosini , Leporati Elisa , Scire Vincenzo , Teobaldi Ilaria , Del Prato Stefano
Published: February 2007

OBJECTIVE—This study was designed to test the safety, effectiveness, and costs of off-loading with a novel, off-the-shelf irremovable device in the management of diabetic foot ulceration (DFU).

RESEARCH DESIGN AND METHODS—We prospectively evaluated off-loading of neuropathic plantar ulcers in 40 diabetic outpatients attending our diabetic foot clinic and compared healing rates at the 12-week follow-up, number and severity of adverse events, healing time, costs and applicability of the device, and patients’ satisfaction between those randomly assigned to total contact casting (TCC; group A) or to the Optima Diab walker (group B). Deep or infected ulcers were excluded.

RESULTS—No difference between groups A and B was observed in healing rates at 12 weeks (95 vs. 85%), healing time (6.5 ± 4.4 vs. 6.7 ± 3.4 weeks), and number of adverse events (six versus four). Treatment was significantly less expensive in group B, which showed a mean reduction of costs of 78% compared with group A (P < 0.001). Practicability was more favorable in group B, with a reduction of 77 and 58% of the time required for application and removal of the devices, respectively (P < 0.001). Patients’ satisfaction with the treatment was higher in group B (P < 0.01).

CONCLUSIONS—The Optima Diab walker is as safe and effective as TCC in the management of DFU, but its lower costs and better applicability may be of help in spreading the practice of off-loading among the centers that manage the diabetic foot.
Insulin Secretion and Insulin Sensitivity in Relation to Fasting Glucose in Healthy Subjects
Authors: Ahrén Bo
Published: February 2007

OBJECTIVE—This study evaluated insulin secretion and insulin sensitivity in healthy subjects with normal fasting glucose.

RESEARCH DESIGN AND METHODS—A total of 148 healthy women (aged 53–70 years) underwent a glucose-dependent arginine stimulation test and a 2-h euglycemic-hyperinsulinemic clamp. In the arginine test, arginine (5 g) was injected intravenously under baseline (fasting) conditions and after raising the glucose levels to 15 and >28 mmol/l. From this test, the acute insulin response (AIR) to arginine during the three glucose levels (AIR1, AIR2, and AIR3) were estimated. The subjects were divided into quartiles of fasting glucose (n = 37 in each group [range <4.32; 4.33–4.84; 4.85–5.22; and 5.23–6.1 mmol/l, respectively).

RESULTS—The results show that 1) AIR1 was higher in subjects in the two highest quartiles (P = 0.004), 2) AIR3 was higher in the quartile with the highest fasting glucose (P = 0.012), and 3) insulin sensitivity was reduced in subjects in the highest quartile (P = 0.026) compared with the lower quartiles. The results also show, in contrast, that AIR2 did not show a similar trend to be increased at higher fasting glucose.

CONCLUSIONS—It is concluded that 1) raised fasting glucose (albeit still within normal values) augments baseline and maximal arginine-induced insulin secretion in healthy subjects, and 2) this is associated with reduced insulin sensitivity. This suggests that high, but still normal, fasting glucose may contribute to the augmented insulin secretion in subjects with low insulin sensitivity.
Factors Influencing Glycemic Control in Type 2 Diabetes During Acute- and Maintenance-Phase Treatment of Major Depressive Disorder With Bupropion
Authors: Lustman Patrick J. , Williams Monique M. , Sayuk Gregory S. , Nix Billy D. , Clouse Ray E.
Published: February 2007

OBJECTIVE—Depression management in both short- and longer-term treatment studies has been associated with improvement in glycemic control. We used bupropion hydrochloride (Wellbutrin XL) to determine whether this improvement could be attributed to changes in anthropometrics or diabetes self-care.

RESEARCH DESIGN AND METHODS—Ninety-three patients with type 2 diabetes and major depressive disorder (MDD) received bupropion hydrochloride in a two-phase, open-label treatment trial. Those who completed the acute phase (10 weeks; n = 75) and whose depression remitted (n = 63) continued bupropion at the remission dose and were followed in the maintenance phase (24 weeks) until attrition (n = 8) or relapse of MDD (n = 0). Self-report scales were used to measure depression symptom severity and diabetes self-care behaviors. Body composition and glycemic control were determined using dual-energy X-ray absorptiometry and serial determinations of A1C.

RESULTS—BMI, total fat mass, and A1C decreased and composite diabetes self-care improved over the acute phase (−0.5 kg/m2, −0.7 kg, −0.5%, and +0.4, respectively, P < 0.01 for each), effects that persisted through the maintenance phase for BMI, A1C, and self-care (P ≤ 0.01 for each). Reductions in BMI (B = 0.30, P = 0.01) and depression severity (B = 0.04, P = 0.046) independently predicted lower A1C after acute-phase treatment, whereas only reduction in depression severity (B = 0.08, P = 0.001) predicted A1C over the maintenance interval.

CONCLUSIONS—In the short term, improvement in glycemic control during bupropion treatment is predicted independently by improvements in mood and body composition. Longer-term improvements in glycemic control are predicted primarily by sustained improvement in mood via mechanisms independent of anthropometric and self-care modifications.
Pesticide Exposure and Self-Reported Gestational Diabetes Mellitus in the Agricultural Health Study
Authors: Saldana Tina M. , Basso Olga , Hoppin Jane A. , Baird Donna D. , Knott Charles , Blair Aaron , Alavanja Michael C.R. , Sandler Dale P.
Published: February 2007

OBJECTIVE—To examine the association between pesticide use during pregnancy and gestational diabetes mellitus (GDM) among wives of licensed pesticide applicators.

RESEARCH DESIGN AND METHODS—Using data from the Agricultural Health Study (AHS), we estimated the association between self-reported pesticide-related activities during the first trimester of the most recent pregnancy and GDM among 11,273 women whose pregnancy occurred within 25 years of enrollment.

RESULTS—A total of 506 (4.5%) women reported having had GDM. Women who reported agricultural pesticide exposure (mixing or applying pesticides to crops or repairing pesticide application equipment) during pregnancy were more likely to report GDM (odds ratio [OR] 2.2 [95% CI 1.5–3.3]). We saw no association between residential pesticide exposure (applying pesticides in the home and garden during pregnancy) and GDM (1.0 [0.8–1.3]). Among women who reported agricultural exposure during pregnancy, risk of GDM was associated with ever-use of four herbicides (2,4,5-T; 2,4,5-TP; atrazine; or butylate) and three insecticides (diazinon, phorate, or carbofuran).

CONCLUSIONS—These findings suggest that activities involving exposure to agricultural pesticides during the first trimester of pregnancy may increase the risk of GDM.
Television Viewing Is Associated With Prevalence of Metabolic Syndrome in Hispanic Elders
Authors: Gao Xiang , Nelson Miriam E. , Tucker Katherine L.
Published: February 2007

OBJECTIVE—We examined associations between television viewing and prevalence of the metabolic syndrome among a representative sample of Caribbean-origin Hispanic elders living in Massachusetts.

RESEARCH DESIGN AND METHODS—We conducted a cross-sectional analysis of 350 Puerto Rican and 105 Dominican elders (≥60 years). Information on television viewing hours was collected by a questionnaire. The metabolic syndrome was defined by using the definition from the National Cholesterol Education Program.

RESULTS—Prevalences for the metabolic syndrome were 50.1 and 56.9% among Puerto Ricans and Dominicans, respectively. Of the subjects, 82.6% had high blood pressure and 61.4% had high fasting glucose. Prevalence of the syndrome was significantly associated with television viewing. Each additional hour of television viewing was associated with a 19% greater likelihood of having the metabolic syndrome (odds ratio [OR] 1.19, 95% CI 1.1–1.3, P for trend 0.002), after adjusting for age, sex, ethnicity, BMI, education, alcohol use, smoking, household arrangement, physical activity, intake of energy and fat, and activities-of-daily-living score. We did not observe significant interactions of television viewing with sex, smoking status, alcohol use, or BMI (P for interaction >0.15 for all) in relation to presence of the metabolic syndrome.

CONCLUSIONS—A high prevalence of the metabolic syndrome in a representative sample of Caribbean-origin Hispanic elders was associated with prolonged television viewing, independent of physical activity and energy intake. Longitudinal studies are needed to clarify the causality of this relationship.
Increasing Incidence of Type 1 Diabetes in 0- to 17-Year-Old Colorado Youth
Authors: Vehik Kendra , Hamman Richard F. , Lezotte Dennis , Norris Jill M. , Klingensmith Georgeanna , Bloch Clifford , Rewers Marian , Dabelea Dana
Published: February 2007

OBJECTIVE—We sought to assess the long-term trends in the incidence of type 1 diabetes among non-Hispanic white and Hispanic youth aged 0–17 years from Colorado using data from the Colorado IDDM Study Registry (1978–1988) and SEARCH for Diabetes in Youth (2002–2004).

RESEARCH DESIGN AND METHODS—Cases of diabetes were ascertained through physician reporting and hospital databases. Type 1 diabetes was defined as use of insulin within 2 weeks from diagnosis. Completeness of ascertainment was estimated as 97%. Annual average incidence rates (per 100,000/year) and 95% CIs for the time periods were computed. Trends in incidence were assessed by Poisson regression.

RESULTS—The incidence of type 1 diabetes was 14.8 (95% CI 14.0–15.6) in 1978–1988 and 23.9 (22.2–25.6) in 2002–2004 for the state of Colorado (P < 0.0001). From 1978 to 2004, the incidence of type 1 diabetes increased by 2.3% (1.6–3.1) per year (P < 0.0001). The increase in incidence was significant for both non-Hispanic white (2.7% [95% CI 1.9–3.6] per year, P < 0.0001) and Hispanic youth (1.6% [0.2–3.1] per year, P = 0.013).

CONCLUSIONS—The incidence of type 1 diabetes has increased 1.6-fold among Colorado youth from 1978–1988 to 2002–2004, and both non-Hispanic white and Hispanic youth are affected by this trend.
Physical Activity of Moderate Intensity and Risk of Type 2 Diabetes
Authors: Jeon Christie Y. , Lokken R. Peter , Hu Frank B. , van Dam Rob M.
Published: February 2007

OBJECTIVE—To systematically evaluate the evidence for an association between physical activity of moderate intensity and risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We searched EMBASE and Medline through March 2006 and examined reference lists of retrieved articles. We excluded studies that did not assess physical activity of moderate intensity independent of activities of vigorous intensity (more than six times the resting metabolic rate). Information on study design, participant characteristics, assessment of physical activity, and outcomes and estimates of associations were extracted independently by two investigators. We calculated summary relative risks (RRs) using a random-effects model for the highest versus the lowest reported duration of activities.

RESULTS—We identified 10 prospective cohort studies of physical activity of moderate intensity and type 2 diabetes, including a total of 301,221 participants and 9,367 incident cases. Five of these studies specifically investigated the role of walking. The summary RR of type 2 diabetes was 0.69 (95% CI 0.58–0.83) for regular participation in physical activity of moderate intensity as compared with being sedentary. Similarly, the RR was 0.70 (0.58–0.84) for regular walking (typically ≥2.5 h/week brisk walking) as compared with almost no walking. The associations remained significant after adjustment for BMI. Similar associations were observed in men and women and in the U.S. and Europe.

CONCLUSIONS—These findings indicate that adherence to recommendations to participate in physical activities of moderate intensity such as brisk walking can substantially reduce the risk of type 2 diabetes.
Insulin Resistance, the Metabolic Syndrome, and Complication Risk in Type 1 Diabetes
Authors: Kilpatrick Eric S. , Rigby Alan S. , Atkin Stephen L.
Published: February 2007

OBJECTIVE—The presence of insulin resistance and the metabolic syndrome are known risk markers for macrovascular disease in patients with and without type 2 diabetes. This study has examined whether these also were predictors of micro- and macrovascular complications in type 1 diabetic patients participating in the Diabetes Control and Complications Trial (DCCT).

RESEARCH DESIGN AND METHODS—International Diabetes Federation (IDF) criteria were used to identify the metabolic syndrome in 1,337 Caucasian DCCT patients at baseline. Insulin resistance was calculated using their estimated glucose disposal rate (eGDR). Insulin dose (units/kg) was also used as a separate marker of insulin resistance.

RESULTS—The eGDR (but not insulin dose or metabolic syndrome) at baseline strongly predicted the development of retinopathy, nephropathy, and cardiovascular disease (hazard ratios 0.75, 0.88, and 0.70, respectively, per mg · kg−1 · min−1 change; P < 0.001, P = 0.005, and P = 0.002, respectively). Through mainly weight gain, the prevalence of the metabolic syndrome increased steadily from baseline to year 9 in conventionally treated (from 15.5 to 27.2%) and especially in the intensively treated (from 13.7 to 45.4%) patients.

CONCLUSIONS—Higher insulin resistance at baseline in the DCCT (as estimated by eGDR) was associated with increased subsequent risk of both micro- and macrovascular complications. Insulin dose and the presence of IDF-defined metabolic syndrome were poor predictors by comparison. Although intensive treatment was associated with a higher subsequent prevalence of metabolic syndrome, the benefits of improved glycemia appear to outweigh the risks related to development of the metabolic syndrome.
Simultaneous Control of Hyperglycemia and Oxidative Stress Normalizes Endothelial Function in Type 1 Diabetes
Authors: Ceriello Antonio , Kumar Sudhesh , Piconi Ludovica , Esposito Katerine , Giugliano Dario
Published: February 2007

OBJECTIVE—Previous studies have shown that in type 1 diabetes endothelial dysfunction persists even when glycemia is normalized. Moreover, oxidative stress has recently been demonstrated to be the mediator of hyperglycemia-induced endothelial dysfunction.

RESEARCH DESIGN AND METHODS—Thirty-six type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near-normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, with achievement of near-normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near-normalization of glycemia.

RESULTS—Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. However, a combination of insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels.

CONCLUSIONS—This study suggests that long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations in endothelial cells, which may contribute to endothelial dysfunction by increased oxidative stress even when hyperglycemia is normalized.
Proteomic Identification of Urinary Biomarkers of Diabetic Nephropathy
Authors: Rao Paturi V. , Lu Xinfang , Standley Melissa , Pattee Patrick , Neelima Gundupalle , Girisesh Gudige , Dakshinamurthy K.V. , Roberts Charles T. , Nagalla Srinivasa R.
Published: February 2007

OBJECTIVE—Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes, and, unless arrested, leads to end-stage renal disease. Current diagnosis consists of urine assays of microalbuminuria, which have inadequate specificity and sensitivity.

RESEARCH DESIGN AND METHODS—We used proteomic analyses to identify novel biomarkers of nephropathy in urine from type 2 diabetic patients with demonstrated normo-, micro-, or macroalbuminuria. Samples were analyzed by fluorescence two-dimensional (2-D) differential in-gel electrophoresis (DIGE), and protein identification was performed by liquid chromatography-tandem mass spectrometry.

RESULTS—2-D DIGE analysis of the urinary proteome in diabetes with nephropathy identified 195 protein spots representing 62 unique proteins. These proteins belonged to several functional groups, i.e., cell development, cell organization, defense response, metabolism, and signal transduction. Comparisons between control and diabetic subjects with different stages of renal dysfunction revealed the differential expression of several proteins. Spot volume quantification identified 7 proteins that were progressively upregulated with increasing albuminuria and 4 proteins that exhibited progressive downregulation. The majority of these potential candidate biomarkers were glycoproteins.

CONCLUSIONS—These data demonstrate the ability of proteomic analyses to reveal potential biomarkers for diabetic nephropathy in urine, an important step forward in advancing accurate diagnosis and our understanding of disease mechanisms.
An Accurate Risk Score Based on Anthropometric, Dietary, and Lifestyle Factors to Predict the Development of Type 2 Diabetes
Authors: Schulze Matthias B. , Hoffmann Kurt , Boeing Heiner , Linseisen Jakob , Rohrmann Sabine , Möhlig Matthias , Pfeiffer Andreas F.H. , Spranger Joachim , Thamer Claus , Häring Hans-Ulrich , Fritsche Andreas , Joost Hans-Georg
Published: February 2007

OBJECTIVE—We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations.

RESEARCH DESIGN AND METHODS—A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35–65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score. Data from the EPIC-Heidelberg, the Tübingen Family Study for Type 2 Diabetes (TÜF), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score.

RESULTS—Information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118–983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were −0.56 in the TÜF and −0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TÜF and 0.75 in the MeSyBePo studies.

CONCLUSIONS—The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes.
Connections between real polynomial solutions of hypergeometric-type differential equations with Rodrigues formula
Authors: Weber Hans
Published: February 2007

Starting from the Rodrigues representation of polynomial solutions of the general hypergeometric-type differential equation complementary polynomials are constructed using a natural method. Among the key results is a generating function in closed form leading to short and transparent derivations of recursion relations and addition theorem. The complementary polynomials satisfy a hypergeometric-type differential equation themselves, have a three-term recursion among others and obey Rodrigues formulas. Applications to the classical polynomials are given.
Electron transport in multilayer structures in a strong magnetic field
Authors: Galbova Olga , Kirichenko Olga , Krstovska Danica , Peschansky Valentin
Published: February 2007

A linear response of the electron system of multilayer conducting structures placed in a strong magnetic field to an external action in the form of an electric field and a temperature gradient is studied theoretically. It is shown that joint investigations of the magnetoresistance and the thermo-emf allows new important information on the structure of the electron energy spectrum to be obtained and the presence of Q1D sheets of the Fermi surface to be revealed.
The impact of tourniquet on patient satisfaction in carpal tunnel decompression
Authors: Nagpal Kamal , Gossiel Mohammed , Kumar Hari
Published: February 2007

Release of the transverse carpal ligament can be performed safely under local anesthesia and without the use of tourniquet. There are conflicting reports for the use of tourniquet in carpal tunnel syndrome. The aim of the study was to compare the patient satisfaction with and without tourniquet in patients with carpal tunnel decompression. This was a retrospective study performed in twenty-four patients who underwent bilateral carpal tunnel decompression. All the patients were diagnosed using a combination of clinical history, clinical tests and EMG recordings.

One side was operated with use of tourniquet and other side without. Patient evaluation measure was used to assess the satisfaction score. A telephonic interview was conducted and patients were asked the questions regarding discomfort caused by tourniquet. The results demonstrated that there was a significant difference in discomfort at the tourniquet site at the time of operation (p<0.00017). Long term, there was no apparent difference in functional outcome of patients operated on with or without tourniquet. There was also no significant difference in subjective sensation, grip or use of hand in patients who underwent carpal tunnel release with or without tourniquet. We conclude that we should not use tourniquet in carpal tunnel decompression.
Structural Transformations during Formation of Quasi‐Amorphous BaTiO3
Authors: Ehre D. , Cohen H. , Lyahovitskaya V. , Tagantsev A. , Lubomirsky I.
Published: February 2007

A model of structural transformations of amorphous into quasi‐amorphous BaTiO3 is suggested. The model is based on previously published data and on X‐ray photoelectron spectroscopy data presented in the current report. Both amorphous and quasi‐amorphous phases of BaTiO3 are made up of a network of slightly distorted TiO6 octahedra connected in three different ways: by apices (akin to perovskite), edges, and faces. Ba ions in these phases are located in the voids between the octahedra, which is a nonperovskite environment. These data also suggest that Ba ions compensate electrical‐charge imbalance incurred by randomly connected octahedra and, thereby, stabilize the TiO6 network. Upon heating, the edge‐to‐edge and face‐to‐face connections between TiO6 octahedra are severed and then reconnected via apices. Severing the connections between TiO6 octahedra requires a volume increase, suppression of which keeps some of the edge‐to‐edge and face‐to‐face connections intact. Transformation of the amorphous thin films into the quasi‐amorphous phase occurs during pulling through a steep temperature gradient. During this process, the volume increase is inhomogeneous and causes both highly anisotropic strain and a strain gradient. The strain gradient favors breaking those connections, which aligns the distorted TiO6 octahedra along the direction of the gradient. As a result, the structure becomes not only anisotropic and non‐centrosymmetric, but also acquires macroscopic polarization. Other compounds may also form a quasi‐amorphous phase, providing that they satisfy the set of conditions derived from the suggested model.
Atherosclerosis and risk for dementia
Authors: van Oijen Marieke , Jan de Jong Frank , Witteman Jacqueline C. M. , Hofman Albert , Koudstaal Peter J. , Breteler Monique M. B.
Published: February 2007

Objective

Atherosclerosis has been implicated in the development of dementia and its major subtypes, Alzheimer's disease and vascular dementia. However, support for this association mainly comes from cross‐sectional studies. We investigated the association of atherosclerosis with dementia and subtypes of dementia during long follow‐up, with various noninvasive measures of atherosclerosis.

Methods

This study was based on 6,647 participants in the Rotterdam Study, a population‐based prospective cohort study among 7,983 elderly subjects. At baseline (1990–1993) and at the third survey (1997–1999), common carotid intima media thickness, carotid plaques, and peripheral arterial disease (measured as ankle–brachial index) were measured. During follow‐up (mean, 9.0 years), 678 subjects developed dementia. We estimated the associations of different measures of atherosclerosis with risk for dementia and subtypes of dementia by means of Cox proportional hazard models. Analyses were repeated and stratified on duration of follow‐up. To evaluate competing risk for mortality, we examined the association between measures of atherosclerosis and risk for dementia or mortality by combining the two in a single outcome measure.

Results

We found that atherosclerosis, predominantly carotid atherosclerosis, was associated with an increased risk for dementia during short follow‐up. This association attenuated with longer follow‐up, likely because of the strong association between atherosclerosis and mortality. The associations did not differ across apolipoprotein E genotypes.

Interpretation

Our findings suggest that atherosclerosis is associated with an increased risk for dementia. Stronger associations between atherosclerosis and mortality may attenuate the association between atherosclerosis and dementia in prospective cohort studies with long follow‐up periods. Ann Neurol 2007
Tracing the Origins and Evolution of Chirality and Handedness in Chemical Language
Authors: Cintas Pedro
Published: February 2007

Chirality, the key concept first proposed by Kelvin, was reintroduced in textbooks in the mid‐1960s. Since then, it has been the source of much reflection and inspiration. This Essay traces the nonchemical origins of the concept and its semantic connotations, which not only enrich the language of chemistry but also have ramifications in, for example, philosophy.
Tribological and mechanical properties of carbon‐nanofiber‐filled polytetrafluoroethylene composites
Authors: Shi Yijun , Feng Xin , Wang Huaiyuan , Lu Xiaohua , Shen Jianyi
Published: February 2007

The effects of various filler concentrations (0.1, 0.5, 1, 1.5, 2, 2.5, and 3 wt %) on the tribological and mechanical properties of carbon‐nanofiber (CNF)‐filled polytetrafluoroethylene (PTFE) composites were studied. Moreover, the influence of various loads (50, 100, 150, and 200 N) and sliding velocities (0.692 and 1.39 m/s) on the friction and wear behaviors of the PTFE composites was investigated. The results showed that the friction coefficients of the PTFE composites decreased initially up to a 0.5 wt % filler concentration and then increased, whereas the antiwear properties of the PTFE composites increased by 1–2 orders of magnitude in comparison with those of pure PTFE. The composite with a 2 wt % filler concentration had the best antiwear properties under all friction conditions. The friction coefficients of the CNF/PTFE composites decreased with increases in the load and sliding velocity, whereas the wear volume loss of the PTFE composites increased. At the same time, the results also indicated that the mechanical properties of the PTFE composites increased first up to a 1 wt % filler concentration and then decreased as the filler concentration was increased above 1 wt %. In comparison with pure PTFE, the impact strength, tensile strength, and elongation to break of the PTFE composites increased by 40, 20, and 70%, respectively, at a 1 wt % filler concentration. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2430–2437, 2007
Reactive extrusion of recycled poly(ethylene terephthalate) with polycarbonate by addition of chain extender
Authors: Tang Xianwen , Guo Weihong , Yin Guorong , Li Binyao , Wu Chifei
Published: February 2007

Poly(ethylene terephthalate) (PET) resin is one of the most widely used engineering plastic with high performance, but the poor impact strength limits its applications for the notch sensitivity. In this research, toughened PET alloy was prepared by blending recycled PET with polycarbonate (PC) and MDI (methylenediphenyl diisocyanate). Intrinsic viscosity and melt viscosity measurements proved increase of the molecular weights of PET via chain‐extending reaction. FTIR and DMA results proved that some PET–PC copolymers were produced and the compatibility of PET phase and PC phase was improved. In addition, the reaction induced by MDI also affected the crystallization behaviors of PET, as observed from DSC results, and the crytallinity of PET decreased with the increase of MDI content. For all of these effects of MDI of increasing of molecular weight, improving of compatibility, and limiting the crystallization behaviors of PET/PC alloy, the notched‐impact strength was greatly improved from 17.3 to 70.5 kJ/m2. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2602–2607, 2007
Synthesis, 1H‐NMR characterization, and biodegradation behavior of aliphatic–aromatic random copolyester
Authors: Chen Xirong , Chen Wei , Zhu Guixiang , Huang Fengxing , Zhang Jingchang
Published: February 2007

Aliphatic‐aromatic copolyesters of poly(butylene adipate‐co‐butylene terephthalate) have been synthesized by polycondensation. Molecular weights and thermal properties have been measured. The four samples of copolyesters, with aromatic contents, varying from 40 to 60 mol %, were investigated by 1H‐NMR spectroscopy to determine copolymers composition and microstructure. For all samples, the biodegradation experiment was carried out in compost, to study copolyesters degradation behavior. Using 1H‐NMR, we noticed that the average sequence length and content of the aliphatic unit decrease and those of the aromatic unit increase. The molecular weights of the samples distinctly drop after composting. In all degraded samples, the trace of growing microorganisms was found on their surfaces by scanning electron microscopy. In combination with the results, the degradation behavior has been studied in the middle stage of copolyester degradation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2643–2649, 2007
A macrophage marker, siglec‐1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type i interferons and toll‐like receptor agonists
Authors: York Michael R. , Nagai Taro , Mangini Alyson J. , Lemaire Raphaël , van Seventer Jean Maguire , Lafyatis Robert
Published: February 2007

Objective

Microarray analyses of peripheral blood leukocytes have shown that patients with systemic lupus erythematosus express increased levels of type I interferon (IFN)–regulated genes. In this study we examined gene expression by peripheral blood mononuclear cells (PBMCs) from patients with systemic sclerosis (SSc) to better understand the dysregulation of the immune system in this disease.

Methods

PBMC gene expression was analyzed by microarray and confirmed by real‐time polymerase chain reaction (PCR). Surface protein expression of Siglec‐1 was analyzed by flow cytometry in PBMCs from healthy control subjects and patients with SSc, and in control PBMCs that were cultured in vitro with Toll‐like receptor (TLR) agonists.

Results

SSc patients showed increased expression of a cluster of IFN‐regulated genes, including Siglec‐1 (CD169, sialoadhesin). This result was verified and extended by real‐time PCR, showing that a subset of the SSc patients expressed strikingly increased levels of Siglec‐1 messenger RNA (mRNA). Flow cytometry of PBMCs from SSc patients and healthy controls showed increased Siglec‐1 surface protein expression, which was restricted to CD14+ monocytes. In vitro studies showed that type I IFN and certain TLR agonists, including TLR‐7 and TLR‐9, induced Siglec‐1 mRNA and protein expression. Moreover, TLR induction of surface Siglec‐1 was shown to be type I IFN–dependent. Increased numbers of Siglec‐1+ cells were observed by immunohistochemistry in the skin of SSc patients compared with healthy controls.

Conclusion

Increased expression of Siglec‐1 in circulating SSc monocytes and tissue macrophages suggests that type I IFN–mediated activation of monocytes occurs in SSc, possibly through TLR activation of IFN secretion. These observations indicate a potential role for type I IFN–activated monocyte/macrophages in the pathogenesis of SSc.
Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis
Authors: Vos Koen , Thurlings Rogier M. , Wijbrandts Carla A. , van Schaardenburg Dirkjan , Gerlag Daniëlle M. , Tak Paul P.
Published: February 2007

Objective

To study the specific effects of rituximab treatment on the synovium in patients with rheumatoid arthritis (RA) early after initiation of treatment.

Methods

Seventeen RA patients underwent an arthroscopic synovial biopsy procedure directly before and 1 month after receiving 2 infusions of the chimeric anti‐CD20 monoclonal antibody rituximab (1,000 mg on days 1 and 15; both without methylprednisolone premedication). Immunohistochemical analysis was performed to characterize the cell infiltrate. Stained tissue sections were analyzed by digital image analysis. Statistical analysis was performed using Wilcoxon's signed rank test.

Results

No significant change in the Disease Activity Score 28‐joint assessment was found at 4 weeks after the first rituximab infusion. At 2 and 4 weeks after infusion, B cells in peripheral blood were almost completely depleted. Most B cells in the synovium were found in large lymphocyte aggregates. Interestingly, a significant reduction in B cell numbers at sites of inflammation was observed 4 weeks after treatment (median 26 cells/mm2 [interquartile range 4–150] before treatment and 11 cells/mm2 [interquartile range 0–29] after treatment; P < 0.02). B cells disappeared completely in 3 patients, whereas there was partial depletion in 11 patients. In the other 3 patients, no B cells were present in biopsy tissues obtained either pretreatment or posttreatment. No reductions in other synovial cell populations were observed at 4 weeks.

Conclusion

Rituximab treatment leads to a rapid and significant decrease in synovial B cell numbers, but not in all patients. Whether the variable tissue response is related to the clinical response over time remains to be clarified.
The diagnostic significance of soluble CD163 and soluble interleukin‐2 receptor α‐chain in macrophage activation syndrome and untreated new‐onset systemic juvenile idiopathic arthritis
Authors: Bleesing Jack , Prada Anne , Siegel David M. , Villanueva Joyce , Olson Judyann , Ilowite Norman T. , Brunner Hermine I. , Griffin Thomas , Graham Thomas B. , Sherry David D. , Passo Murray H. , Ramanan Athimalaipet V. , Filipovich Alexandra , Grom Alexei A.
Published: February 2007

Objective

Macrophage activation syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic macrophages. Levels of soluble interleukin‐2 receptor α (sIL‐2Rα) and soluble CD163 (sCD163) may reflect the degree of activation and expansion of T cells and macrophages, respectively. This study was undertaken to assess the value of serum sIL‐2Rα and sCD163 in diagnosing acute macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (JIA).

Methods

Enzyme‐linked immunosorbent assay was used to assess sIL‐2Rα and sCD163 levels in sera from 7 patients with acute macrophage activation syndrome complicating systemic JIA and 16 patients with untreated new‐onset systemic JIA. The results were correlated with clinical features of established macrophage activation syndrome, including ferritin levels.

Results

The median level of sIL‐2Rα in the patients with macrophage activation syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with macrophage activation syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL‐2Rα or sCD163 were comparable with those in patients with acute macrophage activation syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt macrophage activation syndrome several months later.

Conclusion

Levels of sIL‐2Rα and sCD163 are promising diagnostic markers for macrophage activation syndrome. They may also help identify patients with subclinical macrophage activation syndrome.
Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand
Authors: Burrage Peter S. , Huntington Jonathan T. , Sporn Michael B. , Brinckerhoff Constance E.
Published: February 2007

Objective

To evaluate the effects of LG100268 (LG268), a synthetic ligand for the nuclear hormone receptor retinoid X receptor, on the expression of matrix metalloproteinase 1 (MMP‐1) and MMP‐13 induced by proinflammatory cytokines in a chondrocyte model.

Methods

SW‐1353 human chondrosarcoma cells were used to study the effects of LG268 on interleukin‐1β (IL‐1β)–stimulated MMP production and collagen degradation. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction, and protein levels were determined by Western blot analysis. Collagen degradation was determined by an in vitro matrix destruction assay. The effects of LG268 on nuclear protein binding and histone acetylation were determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively.

Results

LG268 treatment specifically antagonized the IL‐1β–mediated induction of MMP‐1 and MMP‐13 heterogeneous nuclear RNA, messenger RNA, and protein. The inhibitory effect of LG268 was found to be due to a decrease in the rate of MMP‐1 and MMP‐13 transcription. LG268 treatment also prevented the in vitro degradation of a type I collagen matrix by IL‐1β–treated SW‐1353 cells. The inhibitory effect of LG268 on MMP‐1 and MMP‐13 transcription appears to be mediated, at least in part, through modulation of histone modification in regions of the MMP‐1 and MMP‐13 promoters that contain binding sites for activator protein 1 transcription factors.

Conclusion

These data indicate that LG268 treatment selectively inhibits inflammatory cytokine–induced production of MMP‐1 and MMP‐13 at the level of gene transcription and blocks collagen destruction by proinflammatory cytokine–stimulated chondrocytic cells. This study is among the first to describe how rexinoids affect gene expression, and the findings suggest that the rexinoid class of compounds may have a future role in preventing the irreversible collagen destruction seen in the arthritides.
Expression and proinflammatory role of proteinase‐activated receptor 2 in rheumatoid synovium: Ex vivo studies using a novel proteinase‐activated receptor 2 antagonist
Authors: Kelso Elizabeth B. , Ferrell William R. , Lockhart John C. , Elias‐Jones Iona , Hembrough Todd , Dunning Lynette , Gracie J. Alastair , McInnes Iain B.
Published: February 2007

Objective

Serine proteinases activate the G protein–coupled receptor, proteinase‐activated receptor 2 (PAR‐2), via cleavage and exposure of a tethered ligand. PAR‐2 is known to exert proinflammatory actions in a murine model of arthritis, since PAR‐2–deficient mice exhibit strikingly reduced articular inflammation. This study was undertaken to examine synovial PAR‐2 expression and to determine the effect of a novel PAR‐2 antagonist on synovial cytokine production, in order to investigate the hypothesis that PAR‐2 plays a critical role in the pathogenesis of rheumatoid arthritis (RA).

Methods

Using a monoclonal antibody to human PAR‐2, expression in RA synovium and cultured synovial fibroblasts was characterized. The novel PAR‐2 antagonist, ENMD‐1068, was added to primary cultures of RA synovial tissue, from which spontaneous cytokine release was measured.

Results

PAR‐2 was substantially up‐regulated in RA synovium compared with control synovial tissue from patients with osteoarthritis or seronegative inflammatory arthritis, neither of which exhibited significant PAR‐2 expression. Importantly, spontaneous release of tumor necrosis factor α and interleukin‐1β from RA synovium was substantially inhibited by ENMD‐1068, in a dose‐dependent manner.

Conclusion

These findings identify PAR‐2 as a novel upstream regulator of proinflammatory cytokine production in RA and indicate its potential as a novel therapeutic target in inflammatory arthritis.
Increased collagen and aggrecan degradation with age in the joints of Timp3−/− mice
Authors: Sahebjam Solmaz , Khokha Rama , Mort John S.
Published: February 2007

Objective

To investigate the in vivo effect of an imbalance between metalloproteinases and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in mouse articular cartilage.

Methods

Hind joints of Timp3−/− and wild‐type mice were examined by routine staining and by immunohistochemical analysis using antibodies specific for type X collagen and for the neoepitopes produced on proteolytic cleavage of aggrecan (… VDIPEN and … NVTEGE) and type II collagen. The neoepitope generated on cleavage of type II collagen by collagenases was quantitated in sera by enzyme‐linked immunosorbent assay.

Results

Articular cartilage from Timp3‐knockout animals (ages ≥6 months) showed reduced Safranin O staining and an increase in …VDIPEN content compared with cartilage from heterozygous and wild‐type animals. There was also a slight increase in … NVTEGE content in articular cartilage and menisci of Timp3−/− animals. Chondrocytes showed strong pericellular staining for type II collagen cleavage neoepitopes, particularly in the superficial layer, in knockout mice. Also, there was more type X collagen expression in the superficial zone of articular cartilage, especially around clusters of proliferating chondrocytes, in the knockout mice. More type II collagen cleavage product was found in the serum of Timp3−/− mice compared with wild‐type animals. This increase was significant in 15‐month‐old animals.

Conclusion

These results indicate that TIMP‐3 deficiency results in mild cartilage degradation similar to changes seen in patients with osteoarthritis, suggesting that an imbalance between metalloproteinases and TIMP‐3 may play a pathophysiologic role in the development of this disease.
Novel action of n‐3 polyunsaturated fatty acids: Inhibition of arachidonic acid–induced increase in tumor necrosis factor receptor expression on neutrophils and a role for proteases
Authors: Moghaddami Nahid , Irvine James , Gao Xiuhui , Grover Phulwinder K. , Costabile Maurizio , Hii Charles S. , Ferrante Antonio
Published: February 2007

Objective

Neutrophils and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Modulation of TNF receptors (TNFRs) may contribute to the regulation of tissue damage, and n‐6 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) can increase the expression of TNFRI and TNFRII on neutrophils. Because the n‐3 PUFAs are antiinflammatory in RA, we examined whether, as a novel mechanism of action, n‐3 PUFAs can antagonize the AA‐induced increase in TNFR expression.

Methods

Human neutrophils were treated with PUFAs and examined for changes in surface expression of TNFRs by flow cytometry. Translocation of protein kinase C (PKC) and activation of ERK‐1/2 MAPK were determined by Western blotting. Intracellular calcium mobilization was measured in Fura 2–loaded cells by luminescence spectrometry.

Results

Pretreatment of neutrophils with nanomolar levels of n‐3 PUFAs, eicosapentaenoic acid, or docosahexaenoic acid led to a marked inhibition of the AA‐induced up‐regulation of TNFRs I and II. Such pretreatment, however, did not prevent AA from stimulating the activities of PKC and ERK‐1/2, which is required for the actions of AA or its ability to mobilize Ca2+. Nevertheless, treatment with n‐3 PUFAs caused the stimulation of serine proteases that could cleave the TNFRs.

Conclusion

These findings suggest a mechanism by which the n‐3 PUFAs inhibit the inflammatory response in RA, by regulating the ability of AA to increase TNFR expression. These results help fill the gaps in our knowledge regarding the mechanisms of action of n‐3 PUFAs, thus allowing us to make specific recommendations for the use of n‐3 PUFAs in the regulation of inflammatory diseases.
The United States rheumatology workforce: Supply and demand, 2005–2025
Authors: Deal Chad L. , Hooker Roderick , Harrington Timothy , Birnbaum Neal , Hogan Paul , Bouchery Ellen , Klein‐Gitelman Marisa , Barr Walter
Published: February 2007

Objective

To develop and apply a model that allows prediction of current and future supply and demand for rheumatology services in the US.

Methods

A supply model was developed using the age and sex distribution of current physicians, retirement and mortality rates, the number of fellowship slots and fill rates, and practice patterns of rheumatologists. A Markov projection model was used to project needs in 5‐year increments from 2005 to 2025.

Results

The number of rheumatologists for adult patients in the US in 2005 is 4,946. Male and female rheumatologists are equally distributed up to age 44; above age 44, men predominate. The percent of women in adult rheumatology is projected to increase from 30.2% in 2005 to 43.6% in 2025. The mean number of visits per rheumatologist per year is 3,758 for male rheumatologists and 2,800 for female rheumatologists. Assuming rheumatology supply and demand are in equilibrium in 2005, the demand for rheumatologists in 2025 is projected to exceed supply by 2,576 adult and 33 pediatric rheumatologists. The primary factors in the excess demand are an aging population which will increase the number of people with rheumatic disorders, growth in the Gross Domestic Product, and flat rheumatology supply due to fixed numbers entering the workforce and to retirements. The productivity of younger rheumatologists and women, who will make up a greater percentage of the future workforce, may also have important effects on supply. Unknown effects that could influence these projections include technology advances, more efficient practice methods, changes in insurance reimbursements, and shifting lifestyles. Current data suggest that the pediatric rheumatology workforce is experiencing a substantial excess of demand versus supply.

Conclusion

Based on assessment of supply and demand under current scenarios, the demand for rheumatologists is expected to exceed supply in the coming decades. Strategies for the profession to adapt to this changing health care landscape include increasing the number of fellows each year, utilizing physician assistants and nurse practitioners in greater numbers, and improving practice efficiency.