bluuebunny/crossref_metadata_2025_split huggingface dataset:
Road traffic accidents and diabetes: insulin use does not determine risk
Authors: Lonnen K. F. , Powell R. J. , Taylor D. , Shore A. C. , MacLeod K. M. 
Published: April 2008

AbstractAims  Progressive restrictions placed on insulin‐treated patients with diabetes exclude them from driving group 2 and class C1 and D1 vehicles. This reflects an assumption that an increased risk of hypoglycaemia in these patients will cause road traffic accidents. These restrictions have been implemented without any consistent evidence that this is the case. The aim of the study was therefore to investigate whether the rate of road traffic collisions in insulin‐treated patients was higher than that of the non‐diabetic population using a population register‐based study.Methods  A historical cohort study combined information from the Devon and Cornwall Constabulary database on road traffic collisions with the district wide retinal screening database, to provide an anonymized matched database of road traffic collisions in the diabetic population. Accident rates were calculated in the diabetic population and compared to rates in the non‐diabetic population using relative risks.Results  The estimated overall annual accident rate for the non‐diabetic population was 1469 per 100 000 vs. 856 per 100 000 for the diabetic population as a whole (Chi‐squared, P < 0.001). On stratification of the groups by age, within the insulin‐treated group there was no significant difference in the accident rate compared to the non‐diabetic population, with relative risks between 0.51 [confidence interval (CI) 0.25–1.05] and 1.13 (CI 0.88–1.46).Conclusions  Our findings suggest that insulin‐treated patients as a group do not pose an increased risk to road safety. They reiterate the need for an individualized risk‐based assessment when considering driving restrictions.
Impact of 3‐year lifestyle intervention on postprandial glucose metabolism: the SLIM study
Authors: Roumen C. , Corpeleijn E. , Feskens E. J. M. , Mensink M. , Saris W. H. M. , Blaak E. E. 
Published: April 2008

AbstractObjective  To determine the effect of a 3‐year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT).Methods  The study was a randomized controlled lifestyle intervention over 3 years. A total of 147 IGT subjects (75 male, 72 female) were randomized to the intervention (INT) group or control (CON) group; 106 subjects (52 INT, 54 CON) completed 3 years of intervention. Annually, glucose, insulin and free fatty acid (FFA) concentrations were determined fasting and after an oral glucose tolerance test. Measurements of body weight, serum lipids, blood pressure and maximal aerobic capacity were also performed.Results  Analysis of those who completed the 3‐year trial, showed that the lifestyle intervention improved body weight (INT −1.08 ± 4.30 kg; CON +0.16 ± 4.91 kg, P = 0.01), homeostatis model assessment index for insulin resistance and 2‐h FFA. Two‐hour glucose concentrations improved in the INT group, the difference being most pronounced after 1 year, with a return to baseline values after 3 years, from 8.59 ± 1.55 to 8.55 ± 0.34 mm; in contrast, 2‐h glucose deteriorated in the CON group—from 8.46 ± 1.84 to 9.35 ± 2.50 mm (P = 0.02). In the INT group, diabetes incidence was reduced by 58% (P = 0.025).Conclusion  Our lifestyle intervention showed a sustained beneficial effect on 2‐h glucose concentrations, insulin resistance and 2‐h FFA, even after 3 years. Our lifestyle intervention is effective, but for implementation more information is needed about factors influencing adherence.
Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long‐acting insulin in Type 2 diabetes1
Authors: Parkner T. , Laursen T. , Vestergaard E. T. , Hartvig H. , Smedegaard J. S. , Lauritzen T. , Christiansen J. S. 
Published: April 2008

AbstractAims  To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid‐acting insulin analogue and once daily subcutaneous injection of a long‐acting insulin analogue in Type 2 diabetes.Methods  Twenty‐one patients with Type 2 diabetes treated with oral glucose‐lowering agents were randomized in this two‐period crossover study to an equivalent 24‐h dose of continuous subcutaneous infusion of insulin aspart and subsequently once‐daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded.Results  On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre‐injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra‐subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra‐subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic‐only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period.Conclusions  Basal continuous subcutaneous infusion of a rapid‐acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once‐daily subcutaneous injection of a long‐acting insulin analogue in Type 2 diabetes.
Service quality for Type 2 diabetes in Australia: the patient perspective
Authors: Tabrizi J. S. , O’Rourke P. K. , Wilson A. J. , Coyne E. T. 
Published: April 2008

AbstractAims  To assess the service quality of care as perceived by people with Type 2 diabetes mellitus.Methods  A cross‐sectional survey using a self‐administered questionnaire was carried out among members of Diabetes Australia–Queensland with Type 2 diabetes. For 12 aspects of service quality derived from a literature review and focus group research, patients scored the relative importance of the aspects and their perception of quality of received care. A measure of service quality was derived by combining the relative importance and actual performance.Results  A total of 603people with Type 2 diabetes participated. Of the 12 aspects of care, communication, availability of support group, safety and prevention had the highest scores for importance; support group and basic amenities had the highest average performance values; but the highest service quality values were for support group, basic amenities, dignity and confidentiality. Younger participants had lower service quality scores (P = 0.001) and participants with good control of their diabetes had higher scores (P < 0.001). Compared with the reference population, our sample had 8.7% fewer people under 65 years old.Conclusions  From the perspective of people with Type 2 diabetes, there is a notable gap between their expectations and what they have actually received in most aspects of provided care. In addition, overall service quality and six aspects of service quality (choice of care provider, accessibility, prevention, continuity, timeliness and safety) were identified to be of inadequate quality. Hence, this study demonstrates a significant opportunity to improve quality of healthcare services.
An effective system of nurse‐led diabetes care in rural Africa
Authors: Gill G. V. , Price C. , Shandu D. , Dedicoat M. , Wilkinson D. 
Published: April 2008

AbstractAims  Delivering adequate diabetes care is difficult in rural Africa because of drug and equipment shortages; as well as lack of trained medical expertise. We aimed to set up and evaluate a nurse‐led protocol and education‐based system in rural Kwazulu Natal in South Africa.Methods  A treatment algorithm and education system adapted from previously validated methods was used; care was devolved to primary health clinics and was delivered by two nurses. Glycaemic control was assessed by glycated haemoglobin (HbA1c), assayed off site and not available for clinical use during the study.Results  A total of 284 patients were enrolled, with 197 followed for 18 months (13 died and 26% lapsed during the period). HbA1c was 11.6 ± 4.5% (sd) at baseline, 8.7 ± 2.3% at 6 months and 7.7 ± 2.0% at 18 months. There was a small associated increase in weight but no increase in hypoglycaemia. Subgroup analysis showed that education alone, without drug type or dose changes, also improved control (HbA1c 10.6 ± 4.2% baseline and 7.6 ± 2.3% at 18 months). The service was very popular with patients, families and other health workers.Conclusions  We conclude that a simple protocol and education‐based diabetes care system can be successfully introduced and run by nurses in rural Africa. Medium‐term glycaemic improvements are excellent and the service has been very well received.
The high prevalence of unrecognized anaemia in patients with diabetes and chronic kidney disease: a population‐based study
Authors: New J. P. , Aung T. , Baker P. G. , Yongsheng G. , Pylypczuk R. , Houghton J. , Rudenski A. , New R. P. , Hegarty J. , Gibson J. M. , O'Donoghue D. J. , Buchan I. E. 
Published: April 2008

AbstractBackground  Anaemia occurs early in the course of diabetes‐related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population.Methods  Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (< 4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb < 110 g/l or the use of erythropoetic stimulating agents (ESA).Results  Twelve per cent (10–14%) of people had Hb < 110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13–24%) had Hb < 110 g/l. Those with eGFR < 60 ml/min/1.73 m2 and not on ESA or dialysis were four (2–7) times more likely than patients with better renal function to have Hb < 110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3–0.5) g/l fall in haemoglobin.Conclusions  This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.
Comparison of effects of combined ACE inhibitor and low‐dose thiazide diuretic with ACE inhibitor alone on insulin action in patients with hypertension and Type 2 diabetes: a double‐blind crossover study
Authors: McLaughlin D. M. , Atkinson A. B. , Ennis C. N. , Browne J. , Hunter S. J. , Sheridan B. , Bell P. M. 
Published: April 2008

AbstractAims  To establish the safety in terms of insulin sensitivity of a low dose thiazide/ACE inhibitor combination.Methods  We examined the effects on insulin sensitivity of captopril either alone or in combination with low‐dose bendroflumethiazide (1.25 mg) in 15 hypertensive Type 2 diabetic patients. Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double‐blind, randomised, crossover study after a 6‐week placebo run‐in and following two 12‐week treatment periods with captopril (C) (100 mg) alone or in combination with bendroflumethiazide (CB) (1.25 mg).Results  Blood pressure was lower following CB compare to C (138/83 vs. 144/85 mmHg; P < 0.05) and both were lower than baseline (153/92 mmHg; P < 0.01). CB resulted in a significant increase in fasting plasma glucose compared to C (9.6 ± 2.6 vs. 8.5 ± 1.6 mmol/l; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (25.1 ± 13.3 vs. 34.2 ± 16.8 µmol/kg/min; P < 0.01) as were isotopically determined glucose utilisation rates (29.0 ± 12.4 vs. 36.6 ± 17.3 µmol/kg/min; P < 0.05). There was no significant difference in fasting endogenous glucose production between treatments (CB 9.3 ± 3.3 vs. C 8.6 ± 1.6 µmol/kg/min), nor between suppression following insulin (CB 4.0 ± 2.1 vs. C 4.3 ± 3.1 µmol/kg/min).Conclusions  Combination of low‐dose bendroflumethiazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.
Production of cecropin A in transgenic rice plants has an impact on host gene expression
Authors: Campo Sonia , Manrique Silvia , García‐Martínez José , San Segundo Blanca 
Published: April 2008

SummaryExpression of the cecropin A gene in rice confers resistance to the rice blast fungus Magnaporthe oryzae. In this study, a polymerase chain reaction‐based suppression subtractive hybridization approach was used to generate a cDNA macroarray from the elite japonica rice (Oryza sativa L.) cultivar ‘Senia’. Gene expression studies revealed that the expression of components of the protein secretory and vesicular transport machinery is co‐ordinately activated at the pre‐invasive stage of infection of rice by the blast fungus. Comparisons of gene expression between wild‐type and cecropin A plants revealed the over‐expression of genes involved in protection against oxidative stress in transgenic plants in the absence of the pathogen, which correlated well with the tolerance of these plants to oxidative stress. A subcellular fractionation analysis suggested that cecropin A accumulates in the endoplasmic reticulum in cecropin A rice. Moreover, a large number of genes related to the processes of synthesis, folding and stabilization of proteins that enter into the secretory pathway are over‐expressed in cecropin A rice, confirming that these plants constitutively express the unfolded protein response. Transgenic expression of cecropin A in rice has an effect on the transcriptional reprogramming that accompanies plant adaptation to fungal infection. Overall, this study provides evidence for transgene‐induced changes in gene expression in cecropin A rice under both optimal growth conditions and stress conditions imposed by fungal infection. The data also indicate that resistance to blast in cecropin A rice may be the consequence of a combination of the antifungal activity of cecropin A and cecropin A‐mediated over‐expression of rice genes.
FREE RIDERS AND PIOUS SONS – WHY SCIENCE RESEARCH REMAINS OBLIGATORY
Authors: CHAN SARAH , HARRIS JOHN 
Published: April 2008

ABSTRACTJohn Harris has previously proposed that there is a moral duty to participate in scientific research. This concept has recently been challenged by Iain Brassington, who asserts that the principles cited by Harris in support of the duty to research fail to establish its existence. In this paper we address these criticisms and provide new arguments for the existence of a moral obligation to research participation. This obligation, we argue, arises from two separate but related principles. The principle of fairness obliges us to support the social institutions which sustain us, of which research is one; while the principle of beneficence, or the duty of rescue, imposes upon us a duty to prevent harm to others, including by supporting potentially beneficial, even life‐saving research. We argue that both these lines of argument support the duty to research, and explore further aspects of this duty, such as to whom it is owed and how it might be discharged.
WHY WE ARE NOT MORALLY REQUIRED TO SELECT THE BEST CHILDREN: A RESPONSE TO SAVULESCU
Authors: STOLLER SARAH E. 
Published: April 2008

ABSTRACTThe purpose of this paper is to review critically Julian Savulescu's principle of ‘Procreative Beneficence,’ which holds that prospective parents are morally obligated to select, of the possible children they could have, those with the greatest chance of leading the best life. According to this principle, prospective parents are obliged to use the technique of pre‐implantation genetic diagnosis (PGD) to select for the ‘best’ embryos, a decision that ought to be made based on the presence or absence of both disease traits and non‐disease traits such as intelligence. While several articles have been written in response to Savulescu's principle, none has systematically explored its philosophical underpinnings to demonstrate where it breaks down. In this paper I argue that the examples that Savulescu employs to support his theory in fact fail to justify it. He presents these examples as analogous to PGD, when in fact they differ from it in subtle but morally relevant ways. Specifically, Savulescu fails to acknowledge the fact that his examples evoke deontological and virtue ethics concerns that are absent in the context of PGD. These differences turn out to be crucial, so that, in the end, the analogies bear little support for his theory. Finally, I lay out the implications of this analysis for reproductive ethics.
IS THE NAIRU THEORY A MONETARIST, NEW KEYNESIAN, POST KEYNESIAN OR A MARXIST THEORY?
Authors: Stockhammer Engelbert 
Published: April 2008

ABSTRACTThe NAIRU (non‐accelerating inflation rate of unemployment) theory has become the mainstream theory in explaining unemployment in Europe and is often used to justify demands for a cutback of the welfare state, such as reducing unemployment benefits. Close inspection reveals that it, perhaps surprisingly, shares some arguments with Post Keynesian and even Marxist theory. The paper proposes an underdetermined, encompassing NAIRU model, which is consistent with several theoretical traditions. Depending on the closure with respect to demand formation and determination of the NAIRU itself, the model allows for New Keynesian, Post Keynesian and Marxist results.
Targeting of nucleus‐encoded proteins to chloroplasts in plants
Authors: Jarvis Paul 
Published: April 2008

SummaryMost chloroplast proteins are encoded in the nucleus and synthesized on free, cytosolic ribosomes in precursor form. Each precursor has an amino‐terminal extension called a transit peptide, which directs the protein through a post‐translational targeting pathway and is removed upon arrival inside the organelle. This ‘protein import’ process is mediated by the coordinate action of two multiprotein complexes, one in each of the envelope membranes: the TOC and TIC (Translocon at theOuter/Inner envelope membrane ofChloroplasts) machines. Many components of these complexes have been identified biochemically in pea; these include transit peptide receptors, channel proteins, and molecular chaperones. Intriguingly, theArabidopsisgenome encodes multiple, homologous genes for receptor components of the TOC complex. Careful analysis indicated that the different receptor isoforms operate in different import pathways with distinct precursor recognition specificities. These ‘substrate‐specific’ import pathways might play a role in the differentiation of different plastid types, and/or act to prevent deleterious competition effects between abundant and nonabundant precursors. Until recently, all proteins destined for internal chloroplast compartments were thought to possess a cleavable transit peptide, and to engage the TOC/TIC machinery. New studies using proteomics and other approaches have revealed that this is far from true. Remarkably, a significant number of chloroplast proteins are transported via a pathway that involves the endoplasmic reticulum and Golgi apparatus. Other recent reports have elucidated an intriguing array of protein targeting routes leading to the envelope membranes themselves.ContentsSummary257I.Introduction258II.Targeting signals260III.Envelope translocation by the TOC/TIC pathway262IV.Early stages of the TOC/TIC pathway263V.Later stages of the TOC/TIC pathway272VI.Targeting to the envelope system274VII.Alternative or ‘noncanonical’ import pathways276VIII.Conclusion and future perspectives278Acknowledgements278References278
Glutamate induces release of glutathione from cultured rat astrocytes – a possible neuroprotective mechanism?
Authors: Frade João , Pope Simon , Schmidt Maike , Dringen Ralf , Barbosa Rui , Pocock Jennifer , Laranjinha João , Heales Simon 
Published: April 2008

AbstractGlutamate is the major excitatory amino acid of the mammalian brain but can be toxic to neurones if its extracellular levels are not tightly controlled. Astrocytes have a key role in the protection of neurones from glutamate toxicity, through regulation of extracellular glutamate levels via glutamate transporters and metabolic and antioxidant support. In this study, we report that cultures of rat astrocytes incubated with high extracellular glutamate (5 mM) exhibit a twofold increase in the extracellular concentration of the tripeptide antioxidant glutathione (GSH) over 4 h. Incubation with glutamate did not result in an increased release of lactate dehydrogenase, indicating that the rise in GSH was not because of membrane damage and leakage of intracellular pools. Glutamate‐induced increase in extracellular GSH was also independent of de novo GSH synthesis, activation of NMDA and non‐NMDA glutamate receptors or inhibition of extracellular GSH breakdown. Dose–response curves indicate that GSH release from rat astrocytes is significantly stimulated even at 0.1 mM glutamate. The ability of astrocytes to increase GSH release in the presence of extracellular glutamate could be an important neuroprotective mechanism enabling neurones to maintain levels of the key antioxidant, GSH, under conditions of glutamate toxicity.
Identification of multiple post‐translational modifications in the porcine brain specific p25α
Authors: Kleinnijenhuis Anne J. , Hedegaard Claus , Lundvig Ditte , Sundbye Sabrina , Issinger Olaf Georg , Jensen Ole Nørregaard , Jensen Poul Henning 
Published: April 2008

AbstractP25α is a protein normally expressed in oligodendrocytes and subcellular relocalization of p25α occurs in multiple system atrophy, Parkinson’s disease and Lewy body dementia along with ectopic expression in neurons. Moreover, it accumulates in Lewy body inclusions with aggregated α‐synuclein and is a potent stimulator of α‐synuclein aggregation. P25α is a phosphoprotein and post‐translational modifications (PTMs) may play a role in its disease‐related abnormalities. To investigate the spectrum of PTMs on p25α we cloned porcine p25α and isolated the protein from porcine brain. Using several complementary tandem mass spectrometry techniques for peptide mass analysis and amino acid sequencing, a comprehensive analysis of the PTMs on porcine p25α was performed. It was found that porcine p25α is heavily modified with a variety of modifications: phosphorylation, di‐ and trimethylation, citrullination and a HexNAc group. The modifications are localized within p25α’s unfolded terminal domains and suggest that their functional states are regulated. This comprehensive mapping of p25α’s PTMs will form the basis for future functional studies and investigations of p25α’s potential role as a biomarker.