bluuebunny/crossref_metadata_2025 huggingface dataset:
The Public Interest in the Globally Sustainable Information Society: The Traditional Knowledge Debate
Authors: Zografos Daphne
Published: November 2006

Society increasingly perceives information as an owned commodity. As a consequence, laws born from this conception are removing uses of information from the public domain and placing them in an enclosed domain where they are subject to an owner's exclusive control. It has been argued that this enclosure movement poses a threat to the diversity of information sources in our information environment and abridges the freedom of speech. On the other hand, the possibilities of development through the worldwide dissemination and accessibility of information made available by information and communication technology could offer great benefits for developing countries, especially in the field of life sciences, such as medical and agricultural research and development. In this perspective, this article examines where the balance should be struck between private, profit-oriented interests, and the public interest in maintaining some information free for all to use, as well as what should be the role of the public interest in intellectual property policy making. The article examines these questions in the context of the traditional knowledge debate. Over the past few years, the debate over the protection of traditional knowledge by intellectual property rights has attracted the attention of the international community and has prompted increasing scepticism amongst legal scholars, economists and historians. It has been argued that the world has already too much intellectual property and that none of the traditional arguments generally used to justify the creation of intellectual property rights could justify the expansion of the intellectual property rights system to include traditional knowledge. In addition, many argue that traditional knowledge is already in the public domain and should therefore be free for all to use and exploit. On the other hand, traditional knowledge holders wish for defensive protection measures to prevent intellectual property rights claims to their traditional knowledge from being granted to unauthorised persons or corporations as well as positive protection measures to allow them to acquire intellectual property rights over their knowledge, in the form of traditional intellectual property rights, or sui generis rights.
Effects of Autoimmunity and Immune Therapy on β-Cell Turnover in Type 1 Diabetes
Authors: Sherry Nicole A. , Kushner Jake A. , Glandt Mariela , Kitamura Tadahiro , Brillantes Anne-Marie B. , Herold Kevan C.
Published: November 2006

β-Cell mass can expand in response to demand: during pregnancy, in the setting of insulin resistance, or after pancreatectomy. It is not known whether similar β-cell hyperplasia occurs following immune therapy of autoimmune diabetes, but the clinical remission soon after diagnosis and the results of recent immune therapy studies suggest that β-cell recovery is possible. We studied changes in β-cell replication, mass, and apoptosis in NOD mice during progression to overt diabetes and following immune therapy with anti-CD3 monoclonal antibodies (mAbs) or immune regulatory T-cells (Tregs). β-Cell replication increases in pre-diabetic mice, after adoptive transfer of diabetes with increasing islet inflammation but before an increase in blood glucose concentration or a significant decrease in β-cell mass. The pathogenic cells are responsible for increasing β-cell replication because replication was reduced during diabetes remission induced by anti-CD3 mAb or Tregs. β-Cell replication stimulated by the initial inflammatory infiltrate results in increased production of new β-cells after immune therapy and increased β-cell area, but the majority of this increased β-cell area represents regranulated β-cells rather than newly produced cells. We conclude that β-cell replication is closely linked to the islet inflammatory process. A significant proportion of degranulated β-cells remain, at the time of diagnosis of diabetes, that can recover after metabolic correction of hyperglycemia. Correction of the β-cell loss in type 1 diabetes will, therefore, require strategies that target both the immunologic and cellular mechanisms that destroy and maintain β-cell mass.
Skeletal Muscle Mitochondrial Functions, Mitochondrial DNA Copy Numbers, and Gene Transcript Profiles in Type 2 Diabetic and Nondiabetic Subjects at Equal Levels of Low or High Insulin and Euglycemia
Authors: Asmann Yan W. , Stump Craig S. , Short Kevin R. , Coenen-Schimke Jill M. , Guo ZengKui , Bigelow Maureen L. , Nair K. Sreekumaran
Published: November 2006

We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.5 mU/kg of fat-free mass per min, respectively), and glucose. Muscle mitochondrial DNA abundance was not different between type 2 diabetic and nondiabetic subjects at both insulin levels, but the majority of transcripts in muscle that are involved mitochondrial functions were expressed at lower levels in type 2 diabetes at low levels of insulin. However, several gene transcripts that are specifically involved in the electron transport chain were expressed at higher levels in type 2 diabetic patients. After the low-dose insulin infusion, which achieved postabsorptive insulin levels, the muscle mitochondrial ATP production rate (MAPR) was not different between type 2 diabetic and nondiabetic subjects. However, increasing insulin to postprandial levels increased the MAPR in nondiabetic subjects but not in type 2 diabetic patients. The lack of MAPR increment in response to high-dose insulin in type 2 diabetic patients occurred in association with reduced glucose disposal and expression of peroxisome proliferator–activated receptor-γ coactivator 1α, citrate synthase, and cytochrome c oxidase I. In conclusion, the current data supports that muscle mitochondrial dysfunction in type 2 diabetes is not an intrinsic defect, but instead a functional defect related to impaired response to insulin.
Regulation of Pancreatic β-Cell Regeneration in the Normoglycemic 60% Partial-Pancreatectomy Mouse
Authors: Peshavaria Mina , Larmie Brooke L. , Lausier James , Satish Basanthi , Habibovic Aida , Roskens Violet , LaRock Kyla , Everill Brian , Leahy Jack L. , Jetton Thomas L.
Published: November 2006

β-Cell mass is determined by a dynamic balance of proliferation, neogenesis, and apoptosis. The precise mechanisms underlying compensatory β-cell mass (BCM) homeostasis are not fully understood. To evaluate the processes that maintain normoglycemia and regulate BCM during pancreatic regeneration, C57BL/6 mice were analyzed for 15 days following 60% partial pancreatectomy (Px). BCM increased in Px mice from 2 days onwards and was ∼68% of the shams by 15 days, partly due to enhanced β-cell proliferation. A transient ∼2.8-fold increase in the prevalence of β-cell clusters/small islets at 2 days post-Px contributed substantially to BCM augmentation, followed by an increase in the number of larger islets at 15 days. To evaluate the signaling mechanisms that may regulate this compensatory growth, we examined key intermediates of the insulin signaling pathway. We found insulin receptor substrate (IRS)2 and enhanced-activated Akt immunoreactivity in islets and ducts that correlated with increased pancreatic duodenal homeobox (PDX)1 expression. In contrast, forkhead box O1 expression was decreased in islets but increased in ducts, suggesting distinct PDX1 regulatory mechanisms in these tissues. Px animals acutely administered insulin exhibited further enhancement in insulin signaling activity. These data suggest that the IRS2-Akt pathway mediates compensatory β-cell growth by activating β-cell proliferation with an increase in the number of β-cell clusters/small islets.
Differential Effects of p27 in Regulation of β-Cell Mass During Development, Neonatal Period, and Adult Life
Authors: Rachdi Latif , Balcazar Norman , Elghazi Lynda , Barker Daniel J. , Krits Irina , Kiyokawa Hiroaki , Bernal-Mizrachi Ernesto
Published: November 2006

β-Cell cycle progression and proliferation are critical to maintain β-cell mass in adult mice. Of the cell cycle inhibitors, p27Kip1 is thought to be the primary modulator of the proliferative status in most cell types. p27 plays a role in β-cell adaptation in genetic models of insulin resistance. To study the role of p27 in β-cells during physiological conditions and at different stages of β-cell differentiation, we studied mice deficient of or overexpressing p27. Experiments in p27-deficient mice showed improved glucose tolerance and hyperinsulinemia. These changes were associated with increased islet mass and proliferation. The experiments overexpressing p27 in β-cells were performed using a doxycycline-inducible model. Interestingly, overexpression of p27 for 16 weeks in β-cells from adult mice had no effect on glucose tolerance, β-cell mass, or proliferation. In contrast, induction of p27 expression during β-cell development or early neonatal period resulted in severe glucose intolerance and reduced β-cell mass by decreased proliferation. These changes were reversible upon discontinuation of doxycycline. These experiments suggest that p27 is a critical molecule for β-cell proliferation during β-cell development and early postnatal life but not for maintenance of adult mass.
Skin Autofluorescence as a Noninvasive Marker of Vascular Damage in Patients With Type 2 Diabetes
Authors: Lutgers Helen L. , Graaff Reindert , Links Thera P. , Ubink-Veltmaat Lielith J. , Bilo Henk J. , Gans Rijk O. , Smit Andries J.
Published: November 2006

OBJECTIVE—Advanced glycation end products (AGEs) are thought to have a role in the pathogenesis of diabetes complications. We recently reported the association between skin autofluorescence, as a measure of tissue AGE accumulation, and diabetic neuropathy in a selected diabetic population. In this study, we investigated the relation between skin autofluorescence and clinical variables including micro- and macrovascular complications in a type 2 diabetes primary care population.

RESEARCH DESIGN AND METHODS—Clinical data and skin autofluorescence were obtained in the type 2 diabetes group (n = 973) and in a control group (n = 231). Skin autofluorescence was assessed by illumination of the lower arm with a fluorescent tube (peak intensity ∼370 nm).

RESULTS—Skin autofluorescence was significantly higher in type 2 diabetic patients compared with control subjects in each age category. Multiple regression analysis showed significant correlation of skin autofluorescence with age, sex, diabetes duration, BMI, smoking, HbA1c, plasma creatinine, HDL cholesterol, and albumin-to-creatinine ratio in the type 2 diabetes group (R2 = 25%) and with age and smoking in the control group (R2 = 46%). Skin autofluorescence was significantly higher in the type 2 diabetes group, with both micro- and macrovascular disease, compared with the group without complications and the group with only microvascular complications.

CONCLUSIONS—This study confirms in a large group of type 2 diabetic patients that skin autofluorescence is higher compared with age-matched control subjects and is associated with the severity of diabetes-related complications. Skin autofluorescence reflecting vascular damage might be a rapid and helpful tool in the diabetes outpatient clinic for identifying diabetic patients who are at risk for developing complications.
Changes in Inflammatory Cytokines Are Related to Impaired Glucose Tolerance in Offspring of Type 2 Diabetic Subjects
Authors: Ruotsalainen Eija , Salmenniemi Urpu , Vauhkonen Ilkka , Pihlajamäki Jussi , Punnonen Kari , Kainulainen Sakari , Laakso Markku
Published: November 2006

OBJECTIVE—We sought to determine whether levels of inflammatory markers and different cytokines are abnormal in nondiabetic offspring of type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS—Cytokine levels were measured in 19 healthy control subjects and 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance [NGT] and 20 with impaired glucose tolerance [IGT]). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography.

RESULTS—Levels of C-reactive protein and inflammatory cytokines were elevated in nondiabetic offspring of type 2 diabetic subjects. Interleukin (IL)-1β was increased in the NGT group and decreased in the IGT group. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) were increased in both groups. IL-1β and -Ra levels correlated inversely (P < 0.05) with rates of whole-body glucose uptake and IL-1β positively with visceral fat mass (P < 0.05) in normoglycemic offspring.

CONCLUSIONS—Nondiabetic offspring of type 2 diabetic subjects have changes in the levels of inflammatory cytokines. The level of IL-1Ra seems to be the most sensitive marker of cytokine response in the pre-diabetic state.
Early Involvement of the Spinal Cord in Diabetic Peripheral Neuropathy
Authors: Selvarajah Dinesh , Wilkinson Iain D. , Emery Celia J. , Harris Nigel D. , Shaw Pamela J. , Witte Daniel R. , Griffiths Paul D. , Tesfaye Solomon
Published: November 2006

OBJECTIVE—The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN.

RESEARCH DESIGN AND METHODS—Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3.

RESULTS—Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1–70.9] in diabetic subjects without DPN. Those with subclinical (62.4 mm [59.5–65.3]) and clinically detectable DPN (57.2 mm [54.9–59.6]) had lower mean SCAIs compared with subjects with no DPN (P = 0.03 and P < 0.001, respectively). No significant difference was found between diabetic subjects without DPN and nondiabetic control subjects (69.2 mm [66.3–72.0], P = 0.47). Mean SCAIs in subjects with HSMN type 1A (71.07 mm [65.3–76.9]) were not significantly different from those for nondiabetic control subjects and diabetic subjects without DPN. Among diabetic subjects, SCAI was significantly related to sural sensory conduction velocities and the Neuropathy Composite and Symptom Scores.

CONCLUSIONS—Spinal cord involvement occurs early in DPN. There is also a significant relation between reduction in SCAI and neurophysiological assessments of DPN.
Effect of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin as Monotherapy on Glycemic Control in Patients With Type 2 Diabetes
Authors: Aschner Pablo , Kipnes Mark S. , Lunceford Jared K. , Sanchez Matilde , Mickel Carolyn , Williams-Herman Debora E. ,   for the Sitagliptin Study 021 Group
Published: November 2006

OBJECTIVE—To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA1c [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks.

RESULTS—Sitagliptin 100 and 200 mg produced significant (P < 0.001) placebo-subtracted reductions in A1C (−0.79 and −0.94%, respectively) and fasting plasma glucose (−1.0 mmol/l [−17.1 mg/dl] and −1.2 mmol/l [−21.3 mg/dl], respectively). Patients with baseline A1C ≥9% had greater reductions in placebo-subtracted A1C with sitagliptin 100 and 200 mg (−1.52 and −1.50%, respectively) than those with baseline A1C <8% (−0.57 and −0.65%) or ≥8 to <9.0% (−0.80 and −1.13%, respectively). In a meal tolerance test, sitagliptin 100 and 200 mg significantly decreased 2-h postprandial glucose (PPG) (placebo-subtracted PPG −2.6 mmol/l [−46.7 mg/dl] and −3.0 mmol/l [−54.1 mg/dl], respectively). Results for the above key efficacy parameters were not significantly different between sitagliptin doses. Homeostasis model assessment of β-cell function and proinsulin-to-insulin ratio improved with sitagliptin. The incidence of hypoglycemia was similar, and overall gastrointestinal adverse experiences were slightly higher with sitagliptin. No meaningful body weight changes from baseline were observed with sitagliptin 100 (−0.2 kg) or 200 mg (−0.1 kg). The body weight change with placebo (−1.1 kg) was significantly (P < 0.01) different from that observed with sitagliptin.

CONCLUSIONS—In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states, improved measures of β-cell function, and was well tolerated in patients with type 2 diabetes.
Accuracy and Predictive Value of Classification Schemes for Ketosis-Prone Diabetes
Authors: Balasubramanyam Ashok , Garza Gilberto , Rodriguez Lucille , Hampe Christiane S. , Gaur Lakshmi , Lernmark Åke , Maldonado Mario R.
Published: November 2006

OBJECTIVE—Ketosis-prone diabetes (KPD) is an emerging, heterogeneous syndrome. A sound classification scheme for KPD is essential to guide clinical practice and pathophysiologic studies. Four schemes have been used and are based on immunologic criteria, immunologic criteria and insulin requirement, BMI, and immunologic criteria and β-cell function (Aβ classification). The aim of the present study is to compare the four schemes for accuracy and predictive value in determining whether KPD patients have absent or preserved β-cell function, which is a strong determinant of long-term insulin dependence and clinical phenotype.

RESEARCH DESIGN AND METHODS—Consecutive patients (n = 294) presenting with diabetic ketoacidosis and followed for 12–60 months were classified according to all four schemes. They were evaluated longitudinally for β-cell autoimmunity, clinical and biochemical features, β-cell function, and insulin dependence. β-Cell function was defined by peak plasma C-peptide response to glucagon ≥1.5 ng/ml. The accuracy of each scheme to predict absent or preserved β-cell function after 12 months of follow-up was tested using multiple statistical analyses.

RESULTS—The “Aβ” classification scheme was the most accurate overall, with a sensitivity and specificity of 99.4 and 95.9%, respectively, positive and negative likelihood ratios of 24.55 and 0.01, respectively, and an area under the receiver operator characteristic curve of 0.972.

CONCLUSIONS—The Aβ scheme has the highest accuracy and predictive value in classifying KPD patients with regard to clinical outcomes and pathophysiologic subtypes.
Hyperinsulinemia and Cognitive Decline in a Middle-Aged Cohort
Authors: Young Sara E. , Mainous Arch G. , Carnemolla Mark
Published: November 2006

OBJECTIVE—Determining modifiable risks factors for cognitive decline and dementia are a public health priority as we seek to prevent dementia. Type 2 diabetes and related disorders such as hyperinsulinemia increase with aging and are increasing in the U.S. population. Our objective was to determine whether hyperinsulinemia is associated with cognitive decline among middle-aged adults without type 2 diabetes, dementia, or stroke in the Atherosclerosis Risk in Communities (ARIC) cohort.

RESEARCH DESIGN AND METHODS—Middle-aged adults (aged 45–64 years at baseline) in the ARIC cohort had fasting insulin and glucose assessed between 1987 and 1989. Subjects with dementia, type 2 diabetes, or stroke at baseline were excluded from analysis. Three tests of cognitive function available at baseline and 6 years later were delayed word recall (DWR), digit symbol subtest (DSS), and first letter word fluency (WF). Cross-sectional comparisons and linear regression models were computed for cognitive tests at baseline and change in cognitive test scores to determine whether cognitive function was associated with two measures of insulin resistance, fasting insulin and homeostasis model assessment (HOMA). Linear regression models controlled for age, sex, race, marital status, education level, smoking status, alcohol use, depression, hypertension, and hyperlipidemia.

RESULTS—In unadjusted and adjusted analyses, hyperinsulinemia based on fasting insulin and HOMA at baseline was associated with significantly lower baseline DWR, DSS, and WF scores and a greater decline over 6 years in DWR and WF.

CONCLUSIONS—Insulin resistance is a potentially modifiable midlife risk factor for cognitive decline and dementia.
The Metabolic Syndrome Is a Risk Indicator of Microvascular and Macrovascular Complications in Diabetes
Authors:   the Metascreen Writing Committee
Published: November 2006

OBJECTIVE—We aimed at assessing the degree of association and the predictive power of the metabolic syndrome with regard to clinically detectable complications in patients with diabetes.

RESEARCH DESIGN AND METHODS—Metascreen is a cross-sectional survey of metabolic syndrome and clinically detected diabetes complications performed in 8,497 patients (7,859 with type 2 diabetes and 638 with type 1 diabetes) randomly chosen in 176 diabetes outpatient clinics throughout Italy. The metabolic syndrome was defined according to either the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) or the International Diabetes Federation (IDF) diagnostic criteria. Multivariate analyses of the association(s) between either AHA/NHLBI or IDF metabolic syndrome and clinical complications were performed. Receiver-operator characteristic (ROC) curves were constructed to compare the predictive power of the two sets of diagnostic criteria of the metabolic syndrome.

RESULTS—Either definition of the metabolic syndrome was an independent statistical indicator of the presence of nephropathy and neuropathy (P < 0.02–0.01) in type 1 diabetes and of all complications (P < 0.0001), including cardiovascular disease and retinopathy, in type 2 diabetes. For each complication, the ROC curves based on either AHA/NHLBI or IDF metabolic syndrome were similar to each other and to the ROC curves constructed with all continuous traits compounding the metabolic syndrome.

CONCLUSIONS—The metabolic syndrome, defined according to AHA/NHLBI or IDF diagnostic criteria, is an independent clinical indicator and may be involved in the pathogenesis of both macro- and microvascular complications of diabetes.
Age, Sex, and Ethnic Variations in Serum Insulin Concentrations Among U.S. Youth
Authors: Ford Earl S. , Li Chaoyang , Imperatore Giuseppina , Cook Stephen
Published: November 2006

OBJECTIVE—Distributions of serum concentrations of insulin among adolescents and young adults are poorly understood in the U.S. The objective of this study was to describe the distribution of serum insulin across demographic characteristics of U.S. adolescents and young adults.

RESEARCH DESIGN AND METHODS—A total of 1,791 male and female subjects aged 12–19 years who participated in the National Health and Nutrition Examination Surveys for 1999–2002 were included in the analyses.

RESULTS—Among male participants, serum concentrations of insulin increased from age 12 to 14 years before decreasing. Among female participants, concentrations were highest at age 13 years before decreasing steadily through age 19 years. Among participants aged 12–17 years but not those aged 18–19 years, females had higher mean log-transformed concentrations than males (P, Wald, F = 0.038 and 0.125, respectively) after adjusting for age and ethnicity. After adjusting for age and BMI percentile, mean log-transformed concentrations were higher in African-American females aged 12–17 years than in white or Mexican-American participants. No significant ethnic differences were found among female participants aged 18–19 years or male participants aged 12–19 years. Concentrations of insulin increased strongly with increasing levels of BMI.

CONCLUSIONS—These results provide detailed information about serum concentrations of insulin in a representative sample of U.S. adolescents and young adults and may be useful to monitor future trends of this risk factor for diabetes and cardiovascular disease.
Action or Inaction? Decision Making in Patients With Diabetes and Elevated Blood Pressure in Primary Care
Authors: Hicks Paul C. , Westfall John M. , Van Vorst Rebecca F. , Bublitz Emsermann Caroline , Dickinson L. Miriam , Pace Wilson , Parnes Bennett
Published: November 2006

OBJECTIVE—Hypertension increases micro- and macrovascular complications of diabetes. The goal for blood pressure is <130/80 mmHg. In primary care, however, blood pressure in many patients exceeds this goal. In this study, we evaluated the clinical decision-making process when a patient with diabetes presents with elevated blood pressure.

RESEARCH DESIGN AND METHODS—Twenty-six primary care practices in two practice-based research networks in Colorado participated. Questionnaires were completed after each encounter with an adult with type 2 diabetes. Data obtained from the survey included 1) demographic information, 2) blood pressure results, 3) action taken, 4) type of action if action was taken, and 5) reasons for inaction if action was not taken. Bivariate and multivariate analyses were performed to identify predictors of action.

RESULTS—Completed surveys totaled 778. Blood pressure was 130/74 ± 18.8/12.0 mmHg (mean ± SD). Sixty-two percent of patients exceeded goals. Action was taken to lower blood pressure in 34.9% of those. Predictors of action were 1) blood pressure level, 2) total number of medicines the patient was taking, and 3) patient already taking medicines for blood pressure. As blood pressure rose, providers attributed inaction more often to “competing demands” and reasons other than “blood pressure being at or near goal.”

CONCLUSIONS—No evidence was found for patterns of poor care among primary care physicians. Providers balance the clinical circumstances, including how elevated the blood pressure is, and issues of polypharmacy, medication side effects, and costs when determining the best course of action. Knowledge deficit is not a common cause of inaction.
Community Center–Based Resistance Training for the Maintenance of Glycemic Control in Adults With Type 2 Diabetes
Authors: Dunstan David W. , Vulikh Elena , Owen Neville , Jolley Damien , Shaw Jonathan , Zimmet Paul
Published: November 2006

OBJECTIVE—The purpose of this study was to determine whether beneficial effects on glycemic control of an initial laboratory-supervised resistance training program could be sustained through a community center–based maintenance program.

RESEARCH DESIGN AND METHODS—We studied 57 overweight (BMI ≥27 kg/m2) sedentary men and women aged 40–80 years with established (>6 months) type 2 diabetes. Initially, all participants attended a twice-weekly 2-month supervised resistance training program conducted in the exercise laboratory. Thereafter, participants undertook a resistance training maintenance program (2 times/week) for 12 months and were randomly assigned to carry this out either in a community fitness and recreation center (center) or in their domestic environment (home). Glycemic control (HbA1c [A1C]) was assessed at 0, 2, and 14 months.

RESULTS—Pooling data from the two groups for the 2-month supervised resistance training program showed that compared with baseline, mean A1C fell by −0.4% [95% CI −0.6 to −0.2]. Within-group comparisons showed that A1C remained lower than baseline values at 14 months in the center group (−0.4% [−0.7 to −0.03]) but not in the home group (−0.1% [−0.4 to 0.3]). However, no between-group differences were observed at each time point. Changes in A1C during the maintenance period were positively associated with exercise adherence in the center group only.

CONCLUSIONS—Center-based but not home-based resistance training was associated with the maintenance of modestly improved glycemic control from baseline, which was proportional to program adherence. Our findings emphasize the need to develop and test behavioral methods to promote healthy lifestyles including increased physical activity in adults with type 2 diabetes.
Differences in Glucose Tolerance Between Fixed-Dose Antihypertensive Drug Combinations in People With Metabolic Syndrome
Authors: Bakris George , Molitch Mark , Hewkin Ann , Kipnes Mark , Sarafidis Pantelis , Fakouhi Kaffa , Bacher Peter , Sowers James ,   on behalf of the STAR Investigators
Published: November 2006

OBJECTIVE—We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS—A prospective, randomized, open-label, blinded–end points design was used to assess the effects of a T/V versus L/H combination in patients with IGT and hypertension (n = 240) followed for up to 1 year. Doses were titrated to a systolic blood pressure <130 mmHg. Primary outcome was change from baseline in a 2-h glucose on oral glucose tolerance test (OGTT) at study end (mean [±SD] at follow-up, 46.9 ± 13.5 weeks). Secondary outcomes included changes in insulin sensitivity, office and 24-h ambulatory blood pressure, incidence of new-onset diabetes, lipids, and inflammatory markers. Data are expressed as means ± SE unless otherwise noted.

RESULTS—Changes at study end were noted in 2-h OGTT glucose (T/V −0.21 ± 0.36 vs. L/H +1.44 ± 0.36 mmol/l; P < 0.001) and insulin level (−30.13 ± 38.38 vs. +84.86 ± 38.33 pmol/l, respectively; P = 0.025). Worsening of insulin resistance occurred by week 12 (T/V 0.000 ± 0.001 vs. L/H −0.005 ± 0.001; P = 0.016). A higher incidence of new-onset diabetes (T/V 11.0 vs. L/H 26.6%; P = 0.002) and HbA1c >7% (2.6 vs. 9.6%, respectively; P = 0.05) occurred at study end.

CONCLUSIONS—In patients with IGT, normal kidney function, and hypertension, the fixed-dose combination of T/V reduces the risk of new-onset diabetes compared with an L/H-based therapy.
Patient Interpretation of Neuropathy (PIN) Questionnaire
Authors: Vileikyte Loretta , Gonzalez Jeffrey S. , Leventhal Howard , Peyrot Mark F. , Rubin Richard R. , Garrow Adam , Ulbrecht Jan S. , Cavanagh Peter R. , Boulton Andrew J.M.
Published: November 2006

OBJECTIVE—Using the common-sense model of illness behavior, we developed and validated a self-report instrument for assessment of patients’ cognitive and emotional representations of diabetic peripheral neuropathy (DPN) influencing foot self-care.

RESEARCH DESIGN AND METHODS—The Patient Interpretation of Neuropathy (PIN) questionnaire, generated from discussions with clinicians and interviews with patients with DPN, was administered to patients with DPN attending U.K. (n = 325) and U.S. (n = 170) diabetes centers. Psychometric tests of the PIN questionnaire comprised factor analysis, internal consistency, and test-retest reliability. Partial correlations and multivariate regressions established construct and criterion-related validity. The associations of PIN scales to past foot ulceration and foot self-care behaviors were compared with those using a generic measure of illness perception and emotion, the Revised Illness Perception Questionnaire (IPQ-R), which was adapted to neuropathy.

RESULTS—Factor analysis of the PIN questionnaire produced 11 scales, which explained 69% of item variance. Nine factors measured patients’ common-sense beliefs about DPN and their levels of understanding of DPN-related medical information. Two factors assessed the emotions of worry about potential consequences and anger at practitioners. Most scales demonstrated adequate internal (Cronbach’s α = 0.62–0.90) and test-retest reliability (Pearson’s r = 0.51–0.64). Partial correlations between the PIN and IPQ-R scales in corresponding domains were significant but modest (rp = 0.15–0.26). Finally, PIN scales showed significant associations with past foot ulceration and foot self-care behaviors, thereby confirming criterion validity.

CONCLUSIONS—The 39-item PIN questionnaire is a reliable and valid measure of patients’ cognitive and emotional representations of neuropathy affecting foot self-care.
Synthesis of Glyco‐Silicas by Cu(I)‐Catalyzed “Click‐Chemistry” and their Applications in Affinity Chromatography
Authors: Ortega‐Muñoz Mariano , Lopez‐Jaramillo Javier , Hernandez‐Mateo Fernando , Santoyo‐Gonzalez Francisco
Published: November 2006

The covalent immobilization of suitable alkyne/azide carbohydrate derivatives on complementarily functionalizated azide/alkyne silica was performed by click ligation througth the Cu(I)‐catalyzed 1,3‐dipolar cycloaddition reaction of such compounds. The new glyco‐silicas have shown to be efficient and valuable bio‐selective affinity chromatographic supports for the purification of lectins as well as for the one‐pot fluorescent labeling of those proteins. The synthetic methodology is simple, high yielding and flexible, allowing the preparation of tailored glyco‐silicas with potential future applications in the inmobilization of other biomolecules.
Synthesis and Highly Stereoselective Hydrogenation of the Statin Precursor Ethyl (5S)‐5,6‐Isopropylidenedioxy‐3‐oxohexanoate
Authors: Tararov Vitali I. , König Gerd , Börner Armin
Published: November 2006

A search for the large‐scale preparation of (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoates (2) – a key intermediate in the synthesis of pharmacologially important statins – starting from (S)‐malic acid is described. The synthesis of the required initial compound methyl (3S)‐3,4‐(isopropylidenedioxy)butanoate (1) by Moriwake’s reduction of dimethyl (S)‐malate (3) has been improved. Direct 2‐C chain elongation of ester 1 using the lithium enolate of tert‐butyl acetate has been shown to be successful at a 3‐ to 5‐fold excess of the enolate. Unfortunately, the product, tert‐butyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate (2a) is unstable during distillation. Ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate (2b) was prepared alternatively on a multigram scale from (3S)‐3,4‐(isopropylidenedioxy)butanoic acid (7) by activation with N,N′‐carbonyldiimidazole and subsequent reaction with Mg(OOCCH2COOEt)2. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester (2b) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β‐keto ester (2b) to ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐hydrohyhexanoate (syn‐6 and anti‐6) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)‐ and (R)‐BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn‐6/anti‐6=2.3 was observed with an achiral (Ph3P)3RuCl2 catalyst. Ru[(R)‐Tol‐BINAP]Cl2 neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn‐(5S)‐5,6‐isopropylidenedioxy‐3‐hydroxyhexanoate (syn‐6) at a preparative substrate/catalyst ratio of 1000:1.
Enantioselective 1,3‐Dipolar Cycloaddition of Nitrile Imines to α‐Substituted and α,β‐Disubstituted α,β‐Unsaturated Carbonyl Substrates: A Method for Synthesizing Dihydropyrazoles Bearing a Chiral Quaternary Center
Authors: Sibi Mukund P. , Stanley Levi M. , Soeta Takahiro
Published: November 2006

Dihydropyrazoles bearing a chiral quaternary center at the 5‐position have been prepared by enantioselective 1,3‐dipolar cycloaddition of nitrile imines to α‐substituted‐ and α,β‐disubstituted‐α,β‐unsaturated carbonyl substrates. Use of α,β‐unsaturated carbonyl substrates with a 1‐benzyl‐5,5‐dimethylpyrazolidin‐3‐one auxiliary in conjunction with MgI2 and a bisoxazoline ligand derived from (1R,2S)‐(+)‐cis‐1‐amino‐2‐indanol 6 proved optimal to obtain chiral dihydropyrazoles with high enantioselectivity (up to 99 % ee).
Acquired von Willebrand syndrome: An update
Authors: Franchini Massimo , Lippi Giuseppe
Published: November 2006

Acquired von Willebrand syndrome (aVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). However, unlike congenital VWD, it arises in individuals with no personal or family history of bleeding. aVWS occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative disorders, myeloproliferative disorders, and cardiovascular diseases. Through an analysis of the more recent literature data, the pathophysiology and the clinical, laboratory, and therapeutic aspects of this syndrome are concisely reported in this review. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Clearance of the Janus kinase 2 (JAK2) V617F mutation after allogeneic stem cell transplantation in a patient with myelofibrosis with myeloid metaplasia
Authors: Ruiz‐Argüelles Guillermo J. , Garcés‐Eisele Javier , Reyes‐Núñez Virginia , Ruiz‐Delgado Guillermo J. , Rosillo Carlos , Camoriano John K.
Published: November 2006

A patient with myelofibrosis with myeloid metaplasia displaying the V617F mutation of the JAK2 gene was given an allogeneic stem cell transplantation using a reduced‐intensity conditioning regimen. The patient engrafted, and as he became a chimera, the expression of the V617F mutation of the JAK2 gene decreased progressively until its disappearance. Accordingly, the concept of “molecular remission” of the myelofibrosis with myeloid metaplasia could be entertained and added to the categories of response to treatment which have been recently described. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
The study of sequence configuration and functional impact of the (AC)n(AT)xTy motif in human β‐globin gene promoter
Authors: Chan P.K. , Ma E.S.K. , Philipsen S. , Tan‐Un K.C.
Published: November 2006

In this report we examine the (AC)n(AT)xTy motif residing −530 bp 5′ upstream of the β‐globin gene in Chinese thalassaemic patients. This motif is a putative binding site for a repressor protein, termed beta protein 1 (BP1) (Berg et al., Nucleic Acids Res 1989;17:8833–8852). Variations in the (AC)n(AT)xTy repeats affect the binding affinity of BP1, thereby altering the expression of the β‐globin gene. Eight different configurations of this repeat motif are identified in our population of Chinese β‐thalassaemia patients. A (AC)3(AT)7T5 motif was identified among these thalassaemia patients and its influence in β‐globin gene expression was studied using stable transfection assay in murine erythroleukemia (MEL) cells. Our data demonstrated that the (AC)3(AT)7T5 motif has a moderately strong repressor effect on the expression of the cis‐linked β‐globin gene. The high affinity of BP1 for this motif may result in the suppression of the transcription of the β‐globin gene (Berg et al., Am J Hematol 1991;36:42–47). We postulate that silencer elements in the β‐globin promoter play an important role in modifying the clinical presentation of the disease. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
The high incidence of varicella herpes zoster with the use of bortezomib in 10 patients
Authors: Tong Yin , Qian Jie , Li Ying , Meng Hai , Jin Jie
Published: November 2006

Bortezomib, a proteasome inhibitor, has been used for patients with refractory and relapsed multiple myeloma, lymphoma and leukemia. We used bortezomib in ten refractory or relapsed patients (seven of multiple myeloma, two of lymphoma and one of acute myeloblastic leukemia). Six out of ten (60%) patients developed varicella herpes zoster after the complete of one cycle of bortezomib. The incidence of varicella herpes zoster was higher than reported in the literature. It may be due to immunosuppression caused by the combination of high‐dose dexamethasone or other drugs. We considered that prophylactic antiviral medication could be used in predisposed patients to reduce the incidence of varicella herpes zoster. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Morphometric estimation of torsional stiffness and strength in primate mandibles
Authors: Daegling David J.
Published: November 2006

In comparative studies of masticatory function and mandibular biomechanics, the mediolateral dimension of the postcanine corpus (corpus breadth) is commonly utilized as a measure of torsional stiffness from which relative torsional strength is inferred. The use of this dimension entails certain assumptions about corpus shape and cortical bone distribution that are invalid. When corpus breadth is related to an appropriate, empirically supported measure of torsional strength, it is revealed that this dimension has limited utility for inference of biomechanical competence under torsion. The use of linear dimensions to infer structural adaptations to specific loading regimes is problematic given that bone tissue is not optimally deployed to minimize strain levels arising from isolated loads. For the inference of the masticatory biomechanical environment, the more reasonable approach is to consider overall size of the corpus (i.e., cross‐sectional area) for inference of intra‐ and inter‐specific differences in masticatory forces. Am J Phys Anthropol, 2007 © 2006 Wiley‐Liss, Inc.
No signature of Y chromosomal resemblance between possible descendants of the Cimbri in Denmark and Northern Italy
Authors: Børglum Anders D. , Vernesi Cristiano , Jensen Peter K.A. , Madsen Bo , Haagerup Annette , Barbujani Guido
Published: November 2006

Two European populations are believed to be related to the ancient Germanic tribe Cimbri: one living in Northern Italy, the other living in Jutland, Denmark. The people called Cimbri are documented in the ancient Roman historical record. Arriving from the far north their movements can be tracked from successive battles with the Romans. The Cimbri finally entered Italy from the northeast and were defeated at Vercellae (present day Vercelli) in 101 BC by Gaius Marius and his professional legions. Classical sources from the first centuries AD relate the homeland of the Cimbri to the coasts around the Elb estuary (northern Germany) or specifically towards the north (Himmerland in northern Jutland). In the alpine parts of Veneto, northeast of the historical battlefield, local traditions dating back to late medieval time, identify a local population as Cimbri living in Terra dei Cimbri. They are considered the descendents of the Germanic combatants that fled the battlefield at Vercelli. As the defeated Cimbri that possibly fled to the mountains of Northern Italy most likely would have been male (warriors), the present study investigated the possible Y chromosomal diversity of the two present populations using microsatellite markers and single nucleotide polymorphisms. While Cimbri from Himmerland resembled their geographical neighbors from Denmark for the Y‐chromosome markers, Cimbri from Italy were significantly differentiated both from Cimbri from Himmerland and from Danes. Therefore, we were not able to show any biological relationship for uniparentally transmitted markers. Am J Phys Anthropol, 2007 © 2006 Wiley‐Liss, Inc.
Demographic and evolutionary trajectories of the Guarani and Kaingang natives of Brazil
Authors: Marrero Andrea R. , Silva‐Junior Wilson A. , Bravi Cláudio M. , Hutz Mara H. , Petzl‐Erler Maria L. , Ruiz‐Linares Andres , Salzano Francisco M. , Bortolini Maria C.
Published: November 2006

A total of 278 individuals from two Brazilian Indian tribes (Guarani and Kaingang) living in five different localities had their mitochondrial DNA sequenced for the first hypervariable segment (HVS‐I), and a fraction of them was also studied for seven biallelic Y‐chromosome polymorphisms. Nineteen HVS‐I lineages were detected, which showed distinct distributions in the two tribes. The GST value obtained with the mtDNA data is about 5 times higher for the Guarani as compared to the Kaingang, suggesting a higher level of differentiation between the three Guarani partialities than between the two Kaingang villages. Non‐Amerindian admixture varied with sex and in the Guarani was only observed through the paternal line. Using these data and those of other Tupian and Jêan tribes, it was possible to make inferences about past migratory movements and the genetic differentiation of these populations. Am J Phys Anthropol, 2007. © 2006 Wiley‐Liss, Inc.
Genetic studies in French Guiana populations: Synthesis
Authors: Mazières Stéphane , Sevin André , Bonnet Françoise , Crubézy Eric , Salzano Francisco M. , Larrouy Georges
Published: November 2006

Twelve blood group and protein systems from a total of 819 individuals from six tribal groups (Apalaí‐Wayana, Emerillon, Kaliña, Palikur Wayampi, and Wayana) living in French Guiana and Brazil were compared with each other and integrated with previous results from 17 other South Amerindian populations studied for the same genetic markers. Using correspondence analysis, map methodologies, and maximum linkage cluster analysis developed with the UPGMA method, we attempted to establish the genetic position of these tribes among South American Indians. Peripheral positions for the Emerillon and the Palikur were observed. Ethnohistorical data in French Guiana suggest that a strong founder effect for the former and endogamy for the latter could have generated the genetic differentiation of these two ethnic groups. However, when considered in a wider context, all French Guiana Natives cluster together in an intermediate position as compared with 17 other Amerindian groups studied for the comparison. Am J Phys Anthropol, 2007. © 2006 Wiley‐Liss, Inc.
Gold Catalysis
Authors: Hashmi A. Stephen K. , Hutchings Graham J.
Published: November 2006

Catalysis by gold has rapidly become a hot topic in chemistry, with a new discovery being made almost every week. Gold is equally effective as a heterogeneous or a homogeneous catalyst and in this Review we attempt to marry these two facets to demonstrate this new found and general efficacy of gold. The latest discoveries are placed within a historical context, but the main thrust is to highlight the new catalytic possibilities that gold‐catalyzed reactions currently offer the synthetic chemist, in particular in redox reactions and nucleophilic additions to π systems. Indeed gold has proved to be an effective catalyst for many reactions for which a catalyst had not been previously identified, and many new discoveries are still expected.
Binary biopolymeric beads of alginate and gelatin as potential adsorbent for removal of toxic Ni2+ ions: A dynamic and equilibrium study
Authors: Bajpai Jaya , Shrivastava Ruma , Bajpai A. K.
Published: November 2006

Binary biopolymeric beads of alginate and gelatin were prepared and characterized by IR spectral and scanning electron micrograph techniques. On to the surfaces of the prepared beads were performed static and dynamic adsorption studies of Ni2+ ions at fixed pH and ionic strength of the aqueous metal ion solutions. The adsorption data were applied to Langmuir and Freundlich isotherm equations and various static parameters were calculated. The dynamic nature of adsorption was quantified in terms of several kinetic constants such as rate constants for adsorption (k1), Lagergreen rate constant (kad), interparticle diffusion rate constant (kp), and pore diffusion coefficient (D). The influence of various experimental parameters such as solid to liquid ratio, pH, temperature, presence of salts, and chemical composition of biopolymeric beads on the adsorption of nickel ions was investigated. Various thermodynamic parameters were also calculated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2581–2590, 2007