bluuebunny/crossref_metadata_2025 huggingface dataset:
Rural Voters in Presidential Elections, 1992-2004
Authors: McKee Seth C
Published: August 2007

The ``Red" versus ``Blue" state debate has reached a fever pitch in popular commentary, but scholars have contributed very little to the discussion by way of examining rural voting behavior. With the use of national exit poll data, this study attempts to fill this considerable void, with a detailed analysis of rural voters in the 1992-2004 presidential elections. In 1992 and 1996 the rural vote was split between the parties, but in 2000 the rural vote shifted decidedly in favor of Republican George W. Bush and it stayed with the incumbent in 2004. This research on the voting behavior of rural voters in recent presidential elections documents and evaluates the many differences between rural and non-rural voters, and accounts for several of the factors leading to an increase in rural Republican voting in 2000 and 2004. The conventional wisdom that rural voters are more likely to be so-called values voters is true and this translates into greater Republican support. Further, on virtually every survey item in which their non-rural counterparts share the same survey response, rural voters are consistently more Republican in their presidential vote choice. Dissatisfaction with President Clintontermed Clinton fatiguewas much more pronounced among rural voters and this was a major reason for the strong rural shift in favor of the Republican Party in 2000.
Auditioning for President: Fred Thompson, Leading Man or Part Time Player?
Authors: Oppenheimer Bruce I
Published: August 2007

This brief essay assesses the resources and liabilities that Fred Thompson brings to 2008 Republican presidential nomination politics. It examines facets of Thompson's Senate career, as well as his work as a lobbyist and actor. Although Thompson benefits from a political context in which social and religious conservatives find flaws in the first tier candidates and from national visibility, his relatively centrist voting record among Republican senators, reputed, but largely, untested campaign skills, lobbying activities, and late entry in the contest present significant obstacles for him.
Mn-Cu and Mn-Ce Composite Oxides for Decolouration of Acid Red 186 Solutions by CWO
Authors: Castelo-Branco Isabel M. L. , Quinta-Ferreira Rosa M.
Published: August 2007

Decolouration by catalytic oxidation of Acid Red 186 dye solutions was investigated using several manganese-based heterogeneous catalysts, namely MnOx (manganese oxides), Mn-Cu and Mn-Ce composite oxides. Also, catalytic activity of CeO2 and CuOx (copper oxides) were tested. Catalysts were used in slurry conditions, at 130ºC and oxygen partial pressure of 15 bar. Additional uncatalysed run and thermolysis (no catalyst, no oxygen) were studied. The results revealed that MnOx and Mn-Cu were the most active catalysts concerning the reduction of colour. MnCu5 and CuOx led to the highest TOC decreases. From the overall process (colour and TOC reductions) and having in consideration catalyst stability, MnCu5 was considered suitable to AR186 oxidation.
Experimental Design for Two-Color Microarrays Applied in a Pre-Existing Split-Plot Experiment
Authors: Milliken G. A. , Garrett K. A. , Travers S. E.
Published: August 2007

Microarray applications for the study of gene expression are becoming accessible for researchers in more and more systems. Applications from field or laboratory experiments are often complicated by the need to superimpose sample pairing for two-color arrays on experimental designs that may already be complex. For example, split-plot designs are commonly used in biological systems where experiments involve two types of treatments that are not readily applied at the same scale. We demonstrate how effects that are confounded with arrays can still be estimated when there is sufficient replication. To illustrate, we evaluate three methods of sample pairing superimposed on a split-plot design with two treatments, deriving the variance associated with parameter estimates for each. Design A has levels of the whole plot treatment paired on the same microarray within a level of the subplot treatment. Design B has crossed levels paired on the same microarray. Design C has levels of the treatment applied to subplots paired on the same microarray within a whole plot. Designs A and B have lower variance than design C for comparing the levels of the whole plot treatment. Designs B and C have lower variance for comparing the levels of the subplot treatment and design C has lower variance for comparing the levels of the subplot treatment within each level of the whole plot treatment. We provide SAS code for the analyses of variance discussed.
A MINLP Solution for Pellet Reactor Modeling
Authors: Pibouleau Luc Guy , Hocine Sofiane , Azzaro-Pantel Catherine , Domenech Serge
Published: August 2007

A fluidized bed reactor for phosphate precipitation and removal from wastewater is modeled according to a two-step procedure. The first modeling phase, based on the development of a thermodynamic model for the computation of phosphate conversion, previously presented elsewhere is not reported here. The second step is related to the reactor modeling in the core of this paper. The pellet reactor is modeled as a reactor network involving a set of elementary cells representing ideal flow patterns. All the potential solutions are imbedded into a superstructure and the modeling problem is expressed as a MINLP problem. The MINLP problem is solved by means of the GAMS package, first for two flow rate values corresponding to two experimental fluidized bed behaviours, and then for the two flow rates considered simultaneously. In each case, the problem consists in finding an output concentration as close as possible to the experimental output concentration. Three objective functions are studied. The results are compared with those of Montastruc et al. (2004) who used a different numerical procedure. Whatever the considered case, the solutions found are structurally simpler than the ones of Montastruc et al. (2004). A major assessment of this study is that the reactor efficiency can easily be deduced, without any precise knowledge of some key parameters such as the density and thickness of the calcium phosphate layer. Finally a last numerical study concerning the superstructure definition shows that too complex a superstructure does not provide significant refinements on the solution.
Effect of Chromium Supplementation on Glucose Metabolism and Lipids
Authors: Balk Ethan M. , Tatsioni Athina , Lichtenstein Alice H. , Lau Joseph , Pittas Anastassios G.
Published: July 2007

OBJECTIVE—A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels.

RESEARCH DESIGN AND METHODS—A literature search was conducted in MEDLINE and the Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium supplement intake ≥3 weeks, with ≥10 participants receiving chromium. All trials with glucose metabolism outcomes and trials of individuals with diabetes or glucose intolerance for lipid outcomes were included. Meta-analyses were performed as appropriate.

RESULTS—Forty-one studies met criteria, almost half of which were of poor quality. Among participants with type 2 diabetes, chromium supplementation improved glycosylated hemoglobin levels by −0.6% (95% CI −0.9 to −0.2) and fasting glucose by −1.0 mmol/l (−1.4 to −0.5) but not lipids. There was no benefit in individuals without diabetes. There were some indications of dose effect and differences among chromium formulations. Larger effects were more commonly observed in poor-quality studies. The evidence was limited by poor study quality, heterogeneity in methodology and results, and a lack of consensus on assessment of chromium status.

CONCLUSIONS—No significant effect of chromium on lipid or glucose metabolism was found in people without diabetes. Chromium supplementation significantly improved glycemia among patients with diabetes. However, future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.
Prevalence and Management of Diabetes and Associated Risk Factors by Regions of Thailand
Authors: Aekplakorn Wichai , Abbott-Klafter Jesse , Premgamone Amorn , Dhanamun Bodi , Chaikittiporn Chalermchai , Chongsuvivatwong Virasakdi , Suwanprapisa Thanaruk , Chaipornsupaisan Weerayuth , Tiptaradol Siriwat , Lim Stephen S.
Published: July 2007

OBJECTIVE—The aim of this study was to determine the prevalence of diabetes and impaired fasting glucose (IFG) and their association with cardiovascular risk factors and to evaluate the management of blood glucose, blood pressure, and cholesterol in individuals with diabetes by geographical regions of Thailand.

RESEARCH DESIGN AND METHODS—With the use of a stratified, multistage sampling design, data from a nationally representative sample of 37,138 individuals aged ≥15 years were collected using questionnaires, physical examination, and blood samples.

RESULTS—The prevalence of diabetes and IFG weighted to the national 2004 population was 6.7% (6.0% in men and 7.4% in women) and 12.5% (14.7% in men and 10.4% in women), respectively. Diabetes was more common in urban than in rural men but otherwise prevalence was relatively uniform across geographical regions. In more than one-half of those with diabetes, the disease had not been previously diagnosed, although the majority of those with diabetes were treated with oral antiglycemic agents or insulin. The prevalence of associated risk factors was high among individuals with diabetes as well as those with IFG. Two-thirds of those with diabetes and concomitant high blood pressure (≥130/80 mmHg) were not aware that they had high blood pressure, and >70% of those with diabetes and concomitant high cholesterol (total cholesterol ≥6.2 mmol/l) were not aware that they had high cholesterol.

CONCLUSIONS—The prevalences of diabetes and IFG were uniformly high in all regions. Improvements in prevention, diagnosis, and treatment of diabetes and associated risk factors are required if the health burden of diabetes in Thailand is to be averted.
BMI Versus the Metabolic Syndrome in Relation to Cardiovascular Risk in Elderly Chinese Individuals
Authors: He Yao , Jiang Bin , Wang Jie , Feng Kang , Chang Qing , Zhu Shanxiang , Fan Li , Li Xiaoying , Hu Frank B.
Published: July 2007

OBJECTIVE—The purpose of this study was to evaluate the associations of BMI versus metabolic syndrome with cardiovascular diseases (CVDs) in elderly Chinese individuals.

RESEACH DESIGN AND METHODS—We conducted a population-based cross-sectional study in an urban sample of 2,334 elderly subjects (943 men and 1,391 women). Subjects were classified by BMI (≤18.5, <24, <28, and ≥28 kg/m2) and the presence or absence of metabolic syndrome, which was defined by International Diabetes Federation (IDF) criteria. CVDs included clinically diagnosed coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD).

RESULTS—The prevalence rates of overweight (BMI ≥25 kg/m2) and metabolic syndrome according to the IDF criteria were 56.3% (53.9% in men and 57.9% in women) and 46.3% (34.8% in men and 54.1% in women), respectively. Increasing BMI was strongly associated with a higher risk of CHD, stroke, and PAD even after adjustments for metabolic syndrome and other CVD risk factors. Stratified analysis of participants with or without metabolic syndrome showed that BMI was independently associated with CHD, stroke, and PAD.

CONCLUSIONS—Both overweight and metabolic syndrome are highly prevalent in this elderly Chinese population. BMI, as a measure of overall adiposity, is strongly associated with increased prevalence of CVD independent of metabolic syndrome.
Folic Acid Does Not Improve Endothelial Function in Obese Children and Adolescents
Authors: Peña Alexia S. , Wiltshire Esko , Gent Roger , Piotto Lino , Hirte Craig , Couper Jennifer
Published: July 2007

OBJECTIVE—Obese children have severe endothelial dysfunction as measured by flow-mediated dilation (FMD). We have shown that folic acid normalizes endothelial function in children with type 1 diabetes who have a similar degree of endothelial dysfunction but lower total plasma homocyst(e)ine (tHcy) and higher folate status. Our aim was to evaluate, for the first time, the effect of folate supplementation on endothelial dysfunction in obese children.

RESEARCH DESIGN AND METHODS—A total of 53 obese subjects (26 male, mean ± SD age 13.3 ± 2.2 years, and BMI Z score 2.29 ± 0.25) participated in a randomized, double-blind, placebo-controlled, parallel trial of oral folic acid (5 mg/day) or placebo for 8 weeks. Before and after the intervention, we assessed endothelial function (FMD), smooth muscle function (glyceryl trinitrate–induced dilatation [GTN]), high-sensitivity C-reactive protein (hsCRP), tHcy, serum folate, red cell folate (RCF), and lipids.

RESULTS—There were no group differences at baseline. FMD did not change with the intervention (folic acid group pre- and postintervention: 6.42 ± 5.03 and 6.56 ± 4.79%, respectively, vs. placebo group: 5.17 ± 3.54 and 5.79 ± 4.26%, respectively; P = 0.6). Folate supplementation increased serum folate and RCF by 18.4 nmol/l (P < 0.001) and 240.1 nmol/l (P < 0.001), respectively, and decreased tHcy by 0.95 μmol/l (P = 0.008). The intervention did not change GTN, hsCRP, or lipids.

CONCLUSIONS—Folic acid supplementation does not improve endothelial function in obese children without diabetes despite increasing folate status and reducing tHcy. This is in contrast to the response to folate in children with type 1 diabetes.
New Predictive Equations Improve Monitoring of Kidney Function in Patients With Diabetes
Authors: Beauvieux Marie-Christine , Le Moigne Françoise , Lasseur Catherine , Raffaitin Christelle , Perlemoine Caroline , Barthe Nicole , Chauveau Philippe , Combe Christian , Gin Henri , Rigalleau Vincent
Published: July 2007

OBJECTIVE—The Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) equations poorly predict glomerular filtration rate (GFR) decline in diabetic patients. We sought to discover whether new equations based on serum creatinine (the Mayo Clinic Quadratic [MCQ] or reexpressed MDRD equations) or four cystatin C–based equations (glomerular filtration rate estimated via cystatin formula [Cys-eGFR]) were less biased and better predicted GFR changes.

RESEARCH DESIGN AND METHODS—In 124 diabetic patients with a large range of isotopic GFR (iGFR) (56.1 ± 35.3 ml/min per 1.73 m2 [range 5–164]), we compared the performances of the equations before and after categorization in GFR tertiles. A total of 20 patients had a second determination 2 years later.

RESULTS—The Cockcroft-Gault equation was the least precise. The MDRD equation was the most precise but the most biased according to the Bland-Altman procedure. By contrast with the MDRD and, to a lesser extent, the MCQ, three of the four Cys-eGFRs were not biased. All equations overestimated the low GFRs, whereas only the MDRD and Rule's Cys-eGFR equations underestimated the high GFRs. For the subjects studied twice, iGFR changed by −8.5 ± 17.9 ml/min per 1.73 m2. GFR changes estimated by the Cockcroft-Gault (−4.5 ± 6.8) and MDRD (−5.7 ± 6.2) equations did not correlate with the isotopic changes, whereas new equation-predicted changes did: MCQ: −8.7 ± 9.4 (r = 0.44, P < 0.05) and all four Cys-eGFRs: −6.2 ± 7.4 to −7.3 ± 8.4 (r = 0.60 to 0.62, all P < 0.005), such as 100/cystatin-C (r = 0.61, P < 0.005).

CONCLUSIONS—The new predictive equations better estimate GFR than the Cockcroft-Gault equation. Although the MDRD equation remains the most accurate, it poorly predicts GFR decline, as it overestimates low and underestimates high GFRs. This bias is lesser with the MCQ and Cys-eGFR equations, so they better predict GFR changes.
Normoalbuminuric Renal-Insufficient Diabetic Patients
Authors: Rigalleau Vincent , Lasseur Catherine , Raffaitin Christelle , Beauvieux Marie-Christine , Barthe Nicole , Chauveau Philippe , Combe Christian , Gin Henri
Published: July 2007

OBJECTIVE—About 20% of diabetic patients with chronic kidney disease (CKD) detected from the new American Diabetes Association recommendations (albumin excretion rate >30 mg/24 h or estimated glomerular filtration rate [GFR] <60 ml/min per 1.73 m2) may be normoalbuminuric. Do the characteristics and outcome differ for subjects with and without albuminuria?

RESEARCH DESIGN AND METHODS—A total of 89 patients with diabetes and a modification of diet in renal disease (MDRD) estimated GFR (e-GFR) <60 ml/min per 1.73 m2 underwent a 51Cr-EDTA B-isotopic GFR determination and were followed up for 38 ± 11 months.

RESULTS—The mean MDRD e-GFR (41.3 ± 13.1 ml/min per 1.73 m2) did not significantly differ from the i-GFR (45.6 ± 29.7). Of the subjects, 15 (17%) were normoalbuminuric. Their i-GFR did not differ from the albuminuric rate and from their MDRD e-GFR, although their serum creatinine was lower (122 ± 27 vs. 160 ± 71 μmol/l, P < 0.05): 71% would not have been detected by measuring serum creatinine (sCr) alone. They were less affected by diabetic retinopathy, and their HDL cholesterol and hemoglobin were higher (P < 0.05 vs. albuminuric). None of the CKD normoalbuminuric subjects started dialysis (microalbuminuric: 2/36, macroalbuminuric: 10/38) or died (microalbuminuric: 3/36, macroalbuminuric: 7/38) during the follow-up period (log-rank test: P < 0.005 for death or dialysis), and their albumin excretion rate and sCr values were stable after 38 months, whereas the AER increased in the microalbuminuric patients (P < 0.05), and the sCr increased in the macroalbuminuric patients (P < 0.01).

CONCLUSIONS—Although their sCr is usually normal, most of the normoalbuminuric diabetic subjects with CKD according to an MDRD e-GFR below 60 ml/min per 1.73 m2 do really have a GFR below 60 ml/min per 1.73 m2. However, as expected, because of normoalbuminuria and other favorable characteristics, their risk for CKD progression or death is lower.
Thiazolidinediones and Heart Failure
Authors: Singh Sonal , Loke Yoon K. , Furberg Curt D.
Published: July 2007

OBJECTIVE—Thiazolidinediones (TZDs) are known to increase the risk of heart failure in patients with type 2 diabetes. We aimed to evaluate the magnitude of the risk of heart failure with TZDs and classify this adverse effect under the novel dose-time-susceptibility system.

RESEARCH DESIGN AND METHODS—Evidence from randomized trials, controlled observational studies, anecdotal case reports, case series, and spontaneous reports in the Canadian Drug Reaction Monitoring Program (CADRMP) was analyzed in a teleo-analysis.

RESULTS—A random-effects meta-analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1 (95% CI 1.08–4.08; P = 0.03) for the risk of heart failure in patients randomized to TZDs compared with placebo. Four observational studies revealed an OR of 1.55 (1.33–1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility analysis of 28 published reports and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months (with median treatment duration of 24 weeks after initiation of therapy). Heart failure equally occurred at high and low doses. The adverse reaction was not limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in patients aged <60 years.

CONCLUSIONS—Our teleo-analysis confirms the increased magnitude of the risk of heart failure with TZDs. We estimate the number needed to harm with TZDs to be ∼50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk characteristics of TZDs.
A Longitudinal Study of Lipids and Blood Pressure in Relation to Method of Contraception in Latino Women With Prior Gestational Diabetes Mellitus
Authors: Xiang Anny H. , Kawakubo Miwa , Buchanan Thomas A. , Kjos Siri L.
Published: July 2007

OBJECTIVE—To investigate the effect of nonhormonal contraception (NHC), combination oral contraception (COC), and depo-medroxyprogesterone acetate (DMPA) on lipids and blood pressure in women with recent gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—An observational cohort of 972 nondiabetic, normotensive, postpartum Latino women who elected NHC (n = 448), COC (n = 430), or DMPA (n = 94) were followed for at least one subsequent metabolic evaluation on the same contraception. Baseline and follow-up measures included glucose tolerance testing, fasting serum LDL and HDL cholesterol, triglycerides, and systolic (SBP) and diastolic (DBP) blood pressure. Patterns of changes in lipids and blood pressure were evaluated by comparing slopes over follow-up time using random coefficient linear mixed-effects models.

RESULTS—Median follow-up times were 20, 12, and 11 months in the NHC, COC, and DMPA groups. The DMPA users gained significantly more weight (4.3 ± 6.9 kg/year) compared with NHC and COC users (1.2 ± 4.7 and 0.7 ± 6.0 kg/year, respectively; P < 0.0001). Patterns of change in LDL cholesterol, triglycerides, and DBP were not significantly different among groups. HDL cholesterol change differed only between COC and NHC groups (adjusted slopes: 1.0 vs. −1.6 mg · dl−1 · year−1, respectively; P < 0.0001). SBP change differed only between COC and DMPA groups (adjusted slopes: 1.3 vs. −1.7 mmHg/year, respectively; P = 0.01).

CONCLUSIONS—These results, derived predominantly from the initial 1–2 years of treatment in Hispanic women, demonstrate that DMPA was associated with greater weight gain than NHCs or COCs. Other differences in blood pressure and lipid effects were very small. These findings should be taken into account when advising women with recent GDM about their contraceptive choices.
Insulin Resistance
Authors: Lee SoJung , Gungor Neslihan , Bacha Fida , Arslanian Silva
Published: July 2007

OBJECTIVE—We examined the relationship of in vivo insulin sensitivity to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth.

RESEARCH DESIGN AND METHODS—Subjects included 216 youths (8–19 years of age) who participated in a 3-h hyperinsulinemic-euglycemic clamp.

RESULTS—Independent of race, the frequencies of central obesity, high triglycerides, low HDL, high blood pressure, impaired fasting glucose, and impaired glucose tolerance were significantly higher (P < 0.05) in the lowest versus highest quartile of insulin sensitivity. BMI, abdominal adiposity, systolic blood pressure, and triglycerides increased and adiponectin and HDL decreased significantly (P for trend for all <0.05), with decreasing insulin sensitivity in both races. After controlling for BMI, insulin resistance remained associated (P < 0.05) with visceral adipose tissue in both races (P for trend = 0.01 in blacks and 0.08 in whites). In whites but not blacks, lower insulin sensitivity was associated (P < 0.05) with higher intercellular adhesion molecule-1 (ICAM-1) and E-selectin levels; however, these relationships did not remain significant (P > 0.05) once visceral adipose tissue was controlled for.

CONCLUSIONS—The prevalence of the individual components of metabolic syndrome increases with decreasing insulin sensitivity in black and white youth. In whites but not blacks, insulin resistance is associated with increased circulating endothelial biomarkers. It remains to be determined if lower abdominal adiposity and triglycerides in blacks underlies the racial differences in risk translation.
The Prevalence of Cutaneous Manifestations in Young Patients With Type 1 Diabetes
Authors: Pavlović Miloš D. , Milenković Tatjana , Dinić Miroslav , Mišović Milan , Daković Dragana , Todorović Slađana , Đaković Zorana , Zečevi Radoš D. , Doder Radoje
Published: July 2007

OBJECTIVE—The aim of the study was to assess the prevalence of cutaneous disorders and their relation to disease duration, metabolic control, and microvascular complications in children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—The presence and frequency of skin manifestations were examined and compared in 212 unselected type 1 diabetic patients (aged 2–22 years, diabetes duration 1–15 years) and 196 healthy sex- and age-matched control subjects. Logistic regression was used to analyze the relation of cutaneous disorders with diabetes duration, glycemic control, and microvascular complications.

RESULTS—One hundred forty-two (68%) type 1 diabetic patients had at least one cutaneous disorder vs. 52 (26.5%) control subjects (P < 0.01). Diabetes-associated skin lesions were found in 81 (38%) patients. Acquired ichthyosis, rubeosis faciei, diabetic hand, and necrobiosis lipoidica were seen in 22 vs. 3%, 7.1 vs. 0%, 2.3 vs. 0%, and 2.3 vs. 0% of type 1 diabetic and control subjects, respectively. The frequency of cutaneous reactions to insulin therapy was low (–2.7%). The prevalence of fungal infections in patients and control subjects was 4.7% and 1.5%, respectively. Keratosis pilaris affected 12% of our patients vs. 1.5% of control subjects. Diabetic hand was strongly (odds ratio 1.42 [95% CI 1.11–1.81]; P < 0.001), and rubeosis faciei weakly (1.22 [1.04–1.43]; P = 0.0087), associated with diabetes duration. Significant association was also found between acquired ichthyosis and keratosis pilaris (1.53 [1.09–1.79]; P < 0.001).

CONCLUSIONS—Cutaneous manifestations are common in type 1 diabetic patients, and some of them, like acquired ichthyosis and keratosis pilaris, develop early in the course of the disease. Diabetic hand and rubeosis faciei are related to disease duration.
Effect of 2 Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance, and Postprandial Glucose Turnover in Elderly Men
Authors: Basu Rita , Man Chiara Dalla , Campioni Marco , Basu Ananda , Nair K. Sreekumaran , Jensen Michael D. , Khosla Sundeep , Klee George , Toffolo Gianna , Cobelli Claudio , Rizza Robert A.
Published: July 2007

OBJECTIVE—We sought to determine whether, and if so the mechanism by which, testosterone replacement improves carbohydrate tolerance.

RESEARCH DESIGN AND METHODS—Fifty-five elderly men with relative testosterone deficiency ingested a labeled mixed meal and underwent a frequently sampled labeled intravenous glucose tolerance test before and after either placebo or treatment with testosterone patch (5 mg/day) for 2 years.

RESULTS—Despite restoring bioavailable testosterone to values observed in young men, the change (24 months minus baseline values) in fasting and postprandial glucose, insulin, and C-peptide concentrations and meal appearance, glucose disposal, and endogenous glucose production were virtually identical to those observed after 2 years of placebo. The change over time in insulin and C-peptide concentrations post–intravenous glucose injection also did not differ. Furthermore, the change over time in insulin action and glucose effectiveness (measured with the unlabeled and labeled “oral” and “intravenous” minimal models), as well as insulin secretion and hepatic insulin clearance (measured with the C-peptide model), did not differ in the testosterone and placebo groups.

CONCLUSIONS—We conclude that 2 years of treatment with testosterone in elderly men does not improve carbohydrate tolerance or alter insulin secretion, insulin action, glucose effectiveness, hepatic insulin clearance, or the pattern of postprandial glucose metabolism. Thus, testosterone deficiency is unlikely the cause of the age-associated deterioration in glucose tolerance commonly observed in elderly men.
“Damm Sokkor”: Factors Associated With the Quality of Care of Patients With Diabetes
Authors: Alberti Hugh , Boudriga Nessiba , Nabli Mounira
Published: July 2007

OBJECTIVE—To identify the organizational, physician, and patient factors associated with the quality of care of patients with diabetes in a low-/middle-income country.

RESEARCH DESIGN AND METHODS—Data from 2,160 randomly selected patients with diabetes were extracted from the manual medical records of a nationwide sample of 48 randomly selected health centers. Physician and organizational characteristics were collected from national reports, questionnaires, interviews, and observation at the centers. Univariate and multivariate regression analyses were undertaken to identify associations with four quality-of-care scores, based on processes and intermediate outcomes of care and 53 potential explanatory factors.

RESULTS—The mean age of the study population was 62.4 years, mean duration of diabetes was 8.4 years, 62% were female, and 94% had type 2 diabetes. In the final multivariate models, factors independently and significantly associated with higher process-of-care scores were regional affluence, doctor motivation, and the use of chronic disease clinics (P < 0.05). Health centers with younger patients and increased availability of medication were independently and significantly associated with improved outcome-of-care scores (P < 0.05). The final models of the four quality-of-care scores explained 55–71% of the variations in scores.

CONCLUSIONS—Use of chronic disease clinics, availability of medication, and possibly doctor motivation appear to be the most strongly related modifiable factors influencing diabetes care. These findings will be used to develop and implement culturally appropriate quality improvement interventions to improve the quality of diabetes care. We recommend our findings be taken into account in other low-/middle-income countries.
Scottish Foot Ulcer Risk Score Predicts Foot Ulcer Healing in a Regional Specialist Foot Clinic
Authors: Leese Graham , Schofield Christopher , McMurray Brian , Libby Gillian , Golden Judith , MacAlpine Ritchie , Cunningham Scott , Morris Andrew , Flett Murray , Griffiths Gareth
Published: July 2007

OBJECTIVE—To determine whether patients developing ulcers had previously been identified as being at high risk of ulceration using the Scottish Care Information–Diabetes Collaboration (SCI-DC) ulcer risk score and whether the risk score predicts ulcer healing.

RESEARCH DESIGN AND METHODS—All patients attending the diabetes foot clinic with an ulcer had been assessed for foot ulcer risk using the SCI-DC risk calculator, which categorizes patients into low, moderate, or high risk of ulceration. Information on foot pulses, neuropathy, foot deformity, previous ulcer, ulcer site, depth, and presence of sepsis was recorded and related to ulcer outcome. Patients were followed up until outcome was achieved (median 3 months [range 1–33]).

RESULTS—Of patients attending the clinic with a foot ulcer (mean [±SD] age 67.3 ± 12.7 years, 68% male), 68% were previously recognized to be at high risk of foot ulceration, and 98% were high or moderate risk. Of 221 ulcers, the healing rate was 75% overall but was lower for high-risk patients compared with other patients (68 vs. 93%; P < 0.0001). Of the remainder, 3% became chronic ulcers, 12% required minor or major amputation, and 10% died with their ulcer. In multivariate analysis, absent pulses, neuropathy, increased age, and deep ulcers were associated with poor healing. The combination of neuropathy and ischemia was particularly associated with poor outcome of an ulcer (61% healing).

CONCLUSIONS—The Scottish foot ulcer risk score predicts both ulcer development and ulcer healing. The risk score can be a useful initial guide to determine the likelihood of poor healing. The individual criteria contributing to this overall risk are similar to other studies.
Selective solid-phase extraction of Cu(II) using freshly precipitated lead diethyldithiocarbamate and its spectrophotometric determination
Authors: Cesur H.
Published: August 2007

A new solid-phase extraction method has been developed for the selective extraction of Cu(II) in an aqueous system using freshly precipitated lead diethyldithiocarbamate (Pb(DDTC)2) as a reagent. The method is based on the quantitative replacement of Pb(II) ions in the solid Pb(DDTC)2 phase by Cu(II) ions present in aqueous phase. The obtained solid Cu(DDTC)2 phase was dissolved in chloroform and determined spectrophotometrically at 435 nm. Beer’s law was obeyed over the concentration range of 0.2–5 mg dm−3. The molar absorptivity and the Sandell’s sensitivity coefficients of the solutions were 1.0689 × 104 dm3 mol−1 cm−1 and 0.0060 µg cm−2, respectively. The optimum conditions for each parameter were experimentally determined and possible interferences of various salts were also studied. The method has been validated and applied to determine Cu(II) in various alloys and water samples.
Thermal decomposition kinetics of strontium oxalate
Authors: Al-Newaiser F. , Al-Thabaiti S. , Al-Youbi A. , Obaid A. , Gabal M.
Published: August 2007

The thermal decomposition behavior in air of SrC2O4 · 1.25H2O was studied up to the formation of SrO using DTA-TG-DTG techniques. The decomposition proceeds through four well-defined steps. The first two steps are attributed to the dehydration of the salt, while the third and fourth ones are assigned to the decomposition of the anhydrous strontium oxalate into SrCO3 and the decomposition of SrCO3 to SrO, respectively. The exothermic DTA peak found at around 300°C is ascribed to the recrystallization of the anhydrous strontium oxalate. On the other hand, the endothermic DTA peak observed at 910°C can be attributed to the transition of orthorhombic-hexagonal phase of SrCO3. The kinetics of the thermal decomposition of anhydrous strontium oxalate and strontium carbonate, which are formed as stable intermediates, have been studied using non-isothermal TG technique. Analysis of kinetic data was carried out assuming various solid-state reaction models and applying three different computational methods. The data analysis according to the composite method showed that the anhydrous oxalate decomposition is best described by the two-dimensional diffusion-controlled mechanism (D2), while the decomposition of strontium carbonate is best fitted by means of the three-dimensional phase boundary-controlled mechanism (R3). The values of activation parameters obtained using different methods were compared and discussed.
Bimolecular reduction of 9-alkyl-3-nitrocarbazoles
Authors: Kyzioł J.
Published: August 2007

Reduction of 9-alkyl-3-nitrocarbazoles (Ia–Ie) with lithium aluminium hydride gave corresponding 9,9′-dialkyl-3,3′-azocarbazoles (IIa–IIe) in moderate yield. By the action of zinc dust in alcohol and aqueous alkali on I or II, 5,13-dialkyldiindolo[3,2-a,d]phenazines (IIIa–IIId) were obtained. Parent compounds, viz. 3,3′-azocarbazole (IIf) and diindolo[3,2-a,d]phenazine (IIIf) could not be obtained in these ways. Compound IIf was obtained in Vorländer reaction and IIIf by thermal decomposition of 3-azidocarbazole. Formation of IIIa–IIId is explained as a result of ortho-benzidine rearrangement of hypothetical 9,9′-dialkyl-3,3′-hydrazocarbazoles.
A one-pot synthesis of 8-amino-1-methoxy-6H-dibenzo[b,d]pyran-6-one
Authors: Jilani J.
Published: August 2007

8-Amino-1-methoxy-6H-dibenzo[b,d]pyran-6-one was synthesized in a one-pot reaction of 2′,6′-dimethoxy-4-nitro-1,1′-biphenyl-2-carboxylic acid methyl ester using hydroiodic acid as a reagent to effect O-demethylation, lactonization, and nitro reduction to amine. This new reaction represents an improved alternative to the previously reported three-step reactions for this transformation.
Gene Delivery Using Helper Virus–Free HSV‐1 Amplicon Vectors
Authors: Fraefel Cornel
Published: July 2007

Herpes simplex virus type 1 (HSV‐1)‐based amplicon vectors contain only a very small percentage of the 152‐kbp viral genome. Consequently, replication and packaging of amplicons depend on helper functions that are provided either by replication‐defective mutants of HSV‐1 or by replication‐competent, but packaging‐defective, HSV‐1 genomes. Sets of cosmids that overlap and represent the entire HSV‐1 genome can form, via homologous recombination, circular replication‐competent viral genomes, which give rise to infectious virus progeny. However, if the DNA cleavage/packaging signals are deleted, reconstituted virus genomes are not packageable, but still provide all the helper functions required for the packaging of cotransfected amplicon DNA. The resulting stocks of packaged amplicon vectors are essentially free of contaminating helper virus. This unit describes the cotransfection of amplicon and cosmid or bacterial artificial chromosome (BAC) DNA into 2‐2 cells by cationic liposome‐mediated transfection using and the harvesting of packaged vector particles. Support protocols provide methods for preparing cosmid DNA and determining the titers of amplicon stocks. Curr. Protoc. Neurosci. 40:4.14.1‐4.14.21. © by John Wiley & Sons, Inc.
Overview of Gene Targeting by Homologous Recombination
Authors: Mortensen Richard
Published: July 2007

The analysis of mutant organisms and cell lines is important in determining the function of specific proteins. Recent technological advances in gene targeting by homologous recombination in mammalian systems enable the production of mutants in any desired gene, and can be used to produce mutant mouse strains and mutant cell lines. The yeast Flp/FRT recombinase system and bacteriophage recombinases such as Cre and its recognition sequence, loxP, allow spatial and temporal control of knockouts. This unit discusses crucial issues for homologous recombination experiments, including requirements for the source of DNA, criteria for the targeting constructs, methods of enrichment for homologous recombinants, (positive and negative selection, and the use of endogenous promoters), and the types of mutations that can be created. Curr. Protoc. Neurosci. 40:4.29.1‐4.29.13. © by John Wiley & Sons, Inc.
Production of Antisera Using Fusion Proteins
Authors: Dodson Sara E. , Heilman Craig J. , Kahn Richard A. , Levey Allan I.
Published: July 2007

This unit details the use of bacterially produced fusion proteins for the production of antisera, allowing for the large‐scale generation of affinity‐purified antibodies to specific, targeted epitopes. The use of pET vectors containing a polyhistidine (His) or glutathione‐S‐transferase (GST) tag to construct bacterial expression plasmids are provided as prototypical examples of fusion protein methodology. The basic protocols provided in this unit describe: (1) transformation of E. coli for high‐yield production of soluble fusion protein, (2) purification of soluble fusion proteins for use in immunization using chelated nickel or glutathione affinity chromatography (for His‐ and GST‐tagged fusion proteins, respectively), (3) immunization of rabbits with purified fusion protein and collection of antisera, and (4) characterization of antisera for antibody specificity using immunoblotting techniques. Support protocols describe the purification of His‐tagged insoluble fusion proteins for animal immunization and the construction and use of affinity columns for purifying antibodies using soluble fusion proteins. Curr. Protoc. Neurosci. 40:5.7.1‐5.7.26. © by John Wiley & Sons, Inc.
E. coli Genome Manipulation by P1 Transduction
Authors: Thomason Lynn C. , Costantino Nina , Court Donald L.
Published: July 2007

This unit describes the procedure used to move portions of the
E. coli
genome from one genetic variant to another. Fragments of ∼100 kb can be transferred by the P1 bacteriophage. The phage is first grown on a strain containing the elements to be moved, and the resulting phage lysate is used to infect a second recipient strain. The lysate will contain bacterial DNA as well as phage DNA, and genetic recombination, catalyzed by enzymes of the recipient strain, will incorporate the bacterial fragments into the recipient chromosome. Curr. Protoc. Mol. Biol. 79:1.17.1‐1.17.8. © 2007 by John Wiley & Sons, Inc.
Paired‐End diTagging for Transcriptome and Genome Analysis
Authors: Ng Patrick , Wei Chia‐Lin , Ruan Yijun
Published: July 2007

The Paired‐End diTagging (PET) procedure enables one to obtain sequence information from both termini of any contiguous DNA fragment. This is achieved by a series of enzymatic manipulations that introduce MmeI sites directly flanking each DNA insert during the construction of a plasmid library. Subsequent MmeI digestion and self‐ligation results in the production of covalently‐linked paired‐end ditags (PETs) that can be extracted and then concatenated for efficient sequencing. By mapping the PET sequences to assembled genomes, the original DNA fragments from which the PETs were derived can be precisely localized. This unit details two applications of PET technology. In GIS‐PET, ditagging of mRNA converted to full‐length cDNA enables whole‐transcriptome analysis, including novel gene identification, gene prediction validation, and gene expression studies. In ChIP‐PET, ditagging of chromatin immunoprecipitation–enriched genomic DNA fragments enables the global mapping of transcription factor binding sites. A recent innovation (Multiplex Sequencing of Paired‐End ditags; MS‐PET) enables PETs to be sequenced using high‐throughput 454 sequencing, greatly increasing the amount of data that can be collected in each run. Curr. Protoc. Mol. Biol. 79:21.12.1‐21.12.42. © 2007 by John Wiley & Sons, Inc.
Safe Use of Radioisotopes
Authors: Meisenhelder Jill , Bursik Steve
Published: July 2007

The pursuit of scientific knowledge has been considerably advanced by the use of biochemical molecules that incorporate radioisotopes at specific sites. The fate of these labeled molecules, and/or the radiolabeled products that result from biochemical reactions in which the parent molecule was involved, can be traced using a variety of instruments that detect radioactivity. This appendix begins with a discussion of the principles of radioactivity in order to provide the reader/user with knowledge on which to base a common sense approach to the safe use of isotopes. The characteristics of isotopes most commonly used in a molecular biology laboratory are then detailed, as well as the safety precautions and monitoring methods peculiar to each one. Detection and imaging methods used in experimental analysis are reviewed. Finally, an outline of an orderly response to a spill of radioactive material is presented. Curr. Protoc. Mol. Biol. 79:A.1F.1‐A.1F.18. © 2007 by John Wiley & Sons, Inc.
Fosmid Libraries for Genomic Structural Variation Detection
Authors: Donahue William F. , Ebling Heather M.
Published: July 2007

Fosmid libraries have demonstrated their utility for a number of applications. These include filling gaps between BACs and small insert libraries in sequence assemblies, performing hybridization/screening studies to isolate functional elements within the genome (Vergin et al., 1998), and detecting insertions, deletions, and rearrangements in structural variation studies (Tuzun et al., 2005). This unit covers the basic methodologies for the construction of fosmid libraries with tight insert sizes suitable for these applications. Basic Protocol 1 covers the shearing, size selection, and recovery of DNA from a pulsed‐field gel. Basic Protocol 2 covers the cloning of insert DNA into the fosmid vector, packaging of DNA into infective phage particles, and the infection/transformation of bacteria. A commentary section is provided, which outlines many of the critical parameters involved in fosmid library construction, along with some additional background information and a section discussing anticipated results. Curr. Protoc. Hum. Genet. 54:5.20.1‐5.20.18. © 2007 by John Wiley & Sons, Inc.
Analysis of Expression Data: An Overview
Authors: Grewal Anoop , Lambert Peter , Stockton Jordan
Published: July 2007

After providing a brief introduction to microarray chips and experimental details, this overview discusses analysis techniques. Data analysis from microarray experiments generally involves two parts: acquiring and normalizing the data, and interpreting it. This unit focuses mostly on the latter, as it is less technology‐specific.Curr. Protoc. Hum. Genet. 54:11.4.1‐11.4.14. © 2007 by John Wiley & Sons, Inc.
Quantification of Creatine and Guanidinoacetate Using GC‐MS and LC‐MS/MS for the Detection of Cerebral Creatine Deficiency Syndromes
Authors: Young Sarah , Struys Eduard , Wood Tim
Published: July 2007

Inherited defects in creatine biosynthesis and cellular uptake are neurometabolic disorders characterized by seizures, developmental delay, mental retardation, autistic‐like behavior, and creatine deficiency in the brain. Metabolic screening of these disorders is possible using analytical techniques that quantify creatine and its precursor guanidinoacetate in urine, plasma, or cerebrospinal fluid (CSF). Elevated creatine in urine is suggestive of a deficiency of the X‐linked creatine transporter, SLC6A8. Decreased or elevated levels of guanidinoacetate in urine, plasma, or CSF suggest deficiencies of the creatine biosynthetic enzymes, arginine:glycine amidinotransferase (AGAT) or guanidinoacetate methyltransferase (GAMT), respectively. This unit describes three stable isotope dilution–mass spectrometric methods for analyzing creatine and guanidinoacetate. Gas chromatography/mass spectrometry with negative‐ion chemical ionization is a highly sensitive technique, suitable for detection of low analyte levels resulting from AGAT deficiency and in CSF. The two liquid chromatography–tandem mass spectrometric approaches are amenable to high‐throughput screening and have simple sample preparation requirements. Curr. Protoc. Hum. Genet. 54:17.3.1‐17.3.18. © 2007 by John Wiley & Sons, Inc.
Polychromatic Analysis of Mitochondrial Membrane Potential Using JC‐1
Authors: Lugli Enrico , Troiano Leonarda , Cossarizza Andrea
Published: July 2007

Dissipation of the mitochondrial membrane potential (ΔΨm) has been accepted as a hallmark of some apoptotic processes. Depending on the model studied, it can occur during the early stages of cell death or later on, after loss of DNA integrity. Discordant data in the literature could be the consequence of using improper probes such as rhodamine 123 (R123) or DiOC6(3), which are not always appropriate for the study of ΔΨm. The lipophilic cation JC‐1, a specific probe for measuring ΔΨm, is currently the gold standard. Thanks to recently developed instruments and additional probes for cell surface and intracellular markers, it can be used in polychromatic flow cytometric assays to simultaneously detect ΔΨm along with other biological parameters.
High‐Throughput Cytotoxicity Screening by Propidium Iodide Staining
Authors: Edwards Bruce S. , Ivnitski‐Steele Irena , Young Susan M. , Salas Virginia M. , Sklar Larry A.
Published: July 2007

This unit describes a system for the automated high‐throughput analysis of cell cytotoxicity in 96‐well and 384‐well microplates. Discrete cell cultures are analyzed at rates of 40/min (∼2.5 min/96 wells, ∼10 min/384 wells) and cytotoxicity is quantified on the basis of a combination of propidium iodide (PI) fluorescence analysis and cell counting performed by the flow cytometer. Only 2 µl is aspirated from a culture for analysis so that assays can be performed in small volumes to minimize reagent cost and usage.
Live‐Animal Imaging of Renal Function by Multiphoton Microscopy
Authors: Dunn Kenneth W. , Sutton Timothy A. , Sandoval Ruben M.
Published: July 2007

Intravital microscopy, microscopy of living animals, is a powerful research technique that combines the resolution and sensitivity found in microscopic studies of cultured cells with the relevance and systemic influences of cells in the context of the intact animal. The power of intravital microscopy has recently been extended with the development of multiphoton fluorescence microscopy systems capable of collecting optical sections from deep within the kidney at subcellular resolution, supporting high‐resolution characterizations of the structure and function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent probes are administered to an anesthetized, surgically prepared animal, followed by image acquisition for up to 3 hr. Images are transferred via a high‐speed network to specialized computer systems for digital image analysis. This general approach can be used with different combinations of fluorescent probes to evaluate processes such as glomerular permeability, proximal tubule endocytosis, microvascular flow, vascular permeability, mitochondrial function, and cellular apoptosis/necrosis.