Glucagon-like peptide-1 protects beta-cells against apoptosis by increasing the activity of an IGF-2/IGF-1 receptor autocrine loop.

OBJECTIVE: The gluco-incretin hormones glucagon-like peptide (GLP)-1 and gastric inhibitory peptide (GIP) protect beta-cells against cytokine-induced apoptosis. Their action is initiated by binding to specific receptors that activate the cAMP signaling pathway, but the downstream events are not fully elucidated. Here we searched for mechanisms that may underlie this protective effect. RESEARCH DESIGN AND METHODS: We performed comparative transcriptomic analysis of islets from control and GipR(-/-);Glp-1-R(-/-) mice, which have increased sensitivity to cytokine-induced apoptosis. We found that IGF-1 receptor expression was markedly reduced in the mutant islets. Because the IGF-1 receptor signaling pathway is known for its antiapoptotic effect, we explored the relationship between gluco-incretin action, IGF-1 receptor expression and signaling, and apoptosis. RESULTS: We found that GLP-1 robustly stimulated IGF-1 receptor expression and Akt phosphorylation and that increased Akt phosphorylation was dependent on IGF-1 but not insulin receptor expression. We demonstrated that GLP-1-induced Akt phosphorylation required active secretion, indicating the presence of an autocrine activation mechanism; we showed that activation of IGF-1 receptor signaling was dependent on the secretion of IGF-2. We demonstrated, both in MIN6 cell line and primary beta-cells, that reducing IGF-1 receptor or IGF-2 expression or neutralizing secreted IGF-2 suppressed GLP-1-induced protection against apoptosis. CONCLUSIONS: An IGF-2/IGF-1 receptor autocrine loop operates in beta-cells. GLP-1 increases its activity by augmenting IGF-1 receptor expression and by stimulating secretion; this mechanism is required for GLP-1-induced protection against apoptosis. These findings may lead to novel ways of preventing beta-cell loss in the pathogenesis of diabetes.

Factors influencing the adoption of an innovation: an examination of the uptake of the Canadian Heart Health Kit (HHK)

BACKGROUND: There is an emerging knowledge base on the effectiveness of strategies to close the knowledge-practice gap. However, less is known about how attributes of an innovation and other contextual and situational factors facilitate and impede an innovation's adoption. The Healthy Heart Kit (HHK) is a risk management and patient education resource for the prevention of cardiovascular disease (CVD) and promotion of cardiovascular health. Although previous studies have demonstrated the HHK's content validity and practical utility, no published study has examined physicians' uptake of the HHK and factors that shape its adoption. OBJECTIVES: Conceptually informed by Rogers' Diffusion of Innovation theory, and Theory of Planned Behaviour, this study had two objectives: (1) to determine if specific attributes of the HHK as well as contextual and situational factors are associated with physicians' intention and actual usage of the HHK kit; and (2), to determine if any contextual and situational factors are associated with individual or environmental barriers that prevent the uptake of the HHK among those physicians who do not plan to use the kit. METHODS: A sample of 153 physicians who responded to an invitation letter sent to all family physicians in the province of Alberta, Canada were recruited for the study. Participating physicians were sent a HHK, and two months later a study questionnaire assessed primary factors on the physicians' clinical practice, attributes of the HHK (relative advantage, compatibility, complexity, trialability, observability), confidence and control using the HHK, barriers to use, and individual attributes. All measures were used in path analysis, employing a causal model based on Rogers' Diffusion of Innovations Theory and Theory of Planned Behaviour. RESULTS: 115 physicians (follow up rate of 75%) completed the questionnaire. Use of the HHK was associated with intention to use the HHK, relative advantage, and years of experience. Relative advantage and the observability of the HHK benefits were also significantly associated with physicians' intention to use the HHK. Physicians working in solo medical practices reported experiencing more individual and environmental barriers to using the HHK. CONCLUSION: The results of this study suggest that future information innovations must demonstrate an advantage over current resources and the research evidence supporting the innovation must be clearly visible. Findings also suggest that the innovation adoption process has a social element, and collegial interactions and discussions may facilitate that process. These results could be valuable for knowledge translation researchers and health promotion developers in future innovation adoption planning.

An agency-oriented model to explain vine-growing specialization in the province of Barcelona (Catalonia, Spain) in the mid-nineteenth century

[cat] En aquest treball presentem un model per explicar el procés d’especialització vitícola assolit als municipis de la província de Barcelona, a mitjans del s. XIX,que cerca entendre com va sorgir històricament un avantatge comparatiu fruit d’un procés que esdevindria un dels punts de partida del procés d’industrialització a Catalunya. Els resultats confirmen els papers jugats pel impuls “Boserupià” de la població en un context d’intensificació de l’ús de la terra, i d’un impuls del mercat “Smithià” en un context d’expansió de la demanda per part de les economies atlàntiques. També es posa de manifest la importància de les dotacions agro-ecològiques i les condicions socioinstitucionals relacionades amb la desigualtat d’ingrés. La difusió de la vinya donà com a resultat unes comunitats rurals menys desiguals fins al 1820, tot i que aquesta desigualtat augmentà de nou a partir d'aleshores.

Decay of an unstable state in the presence of multiplicative noise

The phenomenon of anomalous fluctuations associated with the decay of an unstable state is analyzed in the presence of multiplicative noise. A theory is presented and compared with a numerical simulation. Our results allow us to distinguish the roles of additive and multiplicative noise in the nonlinear relaxation process. We suggest the use of experiments on transient dynamics to understand the effect of these two sources of noise in problems in which parametric noise is thought to be important, such as dye lasers.

An agency-oriented model to explain vine-growing specialization in the province of Barcelona (Catalonia, Spain) in the mid-nineteenth century

[cat] En aquest treball presentem un model per explicar el procés d’especialització vitícola assolit als municipis de la província de Barcelona, a mitjans del s. XIX,que cerca entendre com va sorgir històricament un avantatge comparatiu fruit d’un procés que esdevindria un dels punts de partida del procés d’industrialització a Catalunya. Els resultats confirmen els papers jugats pel impuls “Boserupià” de la població en un context d’intensificació de l’ús de la terra, i d’un impuls del mercat “Smithià” en un context d’expansió de la demanda per part de les economies atlàntiques. També es posa de manifest la importància de les dotacions agro-ecològiques i les condicions socioinstitucionals relacionades amb la desigualtat d’ingrés. La difusió de la vinya donà com a resultat unes comunitats rurals menys desiguals fins al 1820, tot i que aquesta desigualtat augmentà de nou a partir d'aleshores.

Intestinal and hepatic nitrogen balance in the rat after the administration of an oral protein load

The fate of a small oral dose of protein given to overnight-starved rats was studied. After 3 h, 62 per cent of the protein amino acids had been absorbed. Most of the absorbed N went into the bloodstream through the portal in the form of amino acids, but urea and ammonia were also present. About one-quarter of all absorbed N was carried as lymph amino acids. The liver was able to take all portal free ammonia and a large proportion of portal amino acids, releasing urea. The hepatic N balance was negative, indicating active proteolysis and net loss of liver protein.

Foodborne norovirus outbreak: the role of an asymptomatic food handler

Background: In July 2005 an outbreak of acute gastroenteritis occurred on a residential summer camp in the province of Barcelona (northeast of Spain). Forty-four people were affected among residents and employees. All of them had in common a meal at lunch time on 13 July (paella, round of beef and fruit). The aim of this study was to investigate a foodborne norovirus outbreak that occurred in the residential summer camp and in which the implication of a food handler was demonstrated by laboratory tests. Methods: A retrospective cohort study was designed. Personal or telephone interview was carried out to collect demographic, clinical and microbiological data of the exposed people, as well as food consumption in the suspected lunch. Food handlers of the mentioned summer camp were interviewed. Ten stool samples were requested from symptomatic exposed residents and the three food handlers that prepared the suspected food. Stools were tested for bacteries and noroviruses. Norovirus was detected using RT-PCR and sequence analysis. Attack rate, relative risks (RR) and its 95% confidence intervals (CI) were calculated to assess the association between food consumption and disease. Results: The global attack rate of the outbreak was 55%. The main symptoms were abdominal pain (90%), nausea (85%), vomiting (70%) and diarrhoea (42.5%). The disease remitted in 24-48 hours. Norovirus was detected in seven faecal samples, one of them was from an asymptomatic food handler who had not eaten the suspected food (round of beef), but cooked and served the lunch. Analysis of the two suspected foods isolated no pathogenic bacteria and detected no viruses. Molecular analysis showed that the viral strain was the same in ill patients and in the asymptomatic food handler (genotype GII.2 Melksham-like). Conclusions: In outbreaks of foodborne disease, the search for viruses in affected patients and all food handlers, even in those that are asymptomatic, is essential. Health education of food handlers with respect to hand washing should be promoted.

Combining blockers of the renin-angiotensin system or increasing the dose of an angiotensin II receptor antagonist in proteinuric patients: a randomized triple-crossover study.

Objective The goal of this study was to investigate whether increasing the dose of an angiotensin II receptor blocker (ARB) provides as much benefits as combining the ARB with an angiotensin-converting enzyme inhibitor (ACEI) in terms of blood pressure (BP) control and urinary albumin excretion (UAE) in hypertensive patients with a proteinuria.Methods We enrolled 20 hypertensive patients with proteinuric nephropathies and a reduced renal function in a randomized, 12-month, triple-crossover, prospective, open-label study to compare the effects of a regular dose of losartan (Los 100mg q.d., LOS100) vs. a high dose of losartan (Los 100mg b.i.d., LOS200) vs. losartan 100mg q.d. associated with lisinopril 20 mg q.d. (LOS100 + LIS20). Each treatment was given for 8 weeks with a 4-week initial run-in period and 2 weeks of washout between each treatment phases. 24 h UAE and ambulatory BP were measured during the running phase and at the end of each treatment period.Results Compared to pretreatment, 24 h SBP and DBP were reduced by 10/5 +/- 7/4 mmHg with LOS100 (P=0.023 vs. baseline) and, respectively, 13/6 +/- 12/5 mmHg with LOS200 (P=0.011) and 19/9 +/- 15/8 mmHg with LOS100+LIS20 (P < 0.01). UAE decreased significantly with LOS100 and to an even greater degree with LOS200 and LOS100+LIS20 (P < 0.01 vs. baseline for both and P=0.032, LOS100+LIS20 vs. LOS200). The combination had a greater impact in patients with a high baseline proteinuria as suggested by a nonparallel leftward shift of the relationship between the changes in UAE induced by the combination and those induced by LOS200. The high dose of losartan was better tolerated than the combination.Conclusion Increasing the dose of losartan from 100mg once daily to 100mg twice a day enables to obtain a greater decrease in BP and proteinuria and is better tolerated than combining the ARB with lisinopril, though the high dose appears to be slightly less effective than the combination in patients with a marked proteinuria. J Hypertens 29: 1228-1235 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Severe hypertension following accidental clonidine overdose during the refilling of an implanted intrathecal drug delivery system.

BACKGROUND:   Complications associated with intrathecal pumps may be linked to the surgical procedure, the implanted device, or the medication itself.¦CASE REPORTS:   Three patients treated chronically with intrathecal clonidine presented with clonidine overdose due to inadvertent extravasation during the refilling procedure. All patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment.¦DISCUSSION:   Clonidine is an alpha-2 agonist with a nearly 100% bioavailability after oral or rectal administration. With high plasma concentration secondary to massive systemic overdose, the specificity for the alpha-2 receptor is lost and an alpha-1 agonist activity predominates and causes marked hypertension. Management of clonidine overdose consists of supportive therapy guided by signs and symptoms.¦CONCLUSION:   Inadvertent injection into the subcutaneous pocket rather than the reservoir is rare but very dangerous as the drug cannot be retrieved and massive doses are involved. Signs and symptoms of systemic overdose with drugs commonly used in implanted drugs delivery system should be well known to ensure early diagnosis and treatment.

The development of an automatic recognition system for earmark and earprint comparisons

The value of earmarks as an efficient means of personal identification is still subject to debate. It has been argued that the field is lacking a firm systematic and structured data basis to help practitioners to form their conclusions. Typically, there is a paucity of research guiding as to the selectivity of the features used in the comparison process between an earmark and reference earprints taken from an individual. This study proposes a system for the automatic comparison of earprints and earmarks, operating without any manual extraction of key-points or manual annotations. For each donor, a model is created using multiple reference prints, hence capturing the donor within source variability. For each comparison between a mark and a model, images are automatically aligned and a proximity score, based on a normalized 2D correlation coefficient, is calculated. Appropriate use of this score allows deriving a likelihood ratio that can be explored under known state of affairs (both in cases where it is known that the mark has been left by the donor that gave the model and conversely in cases when it is established that the mark originates from a different source). To assess the system performance, a first dataset containing 1229 donors elaborated during the FearID research project was used. Based on these data, for mark-to-print comparisons, the system performed with an equal error rate (EER) of 2.3% and about 88% of marks are found in the first 3 positions of a hitlist. When performing print-to-print transactions, results show an equal error rate of 0.5%. The system was then tested using real-case data obtained from police forces.

Manipulation of salicylate content in Arabidopsis thaliana by the expression of an engineered bacterial salicylate synthase.

Salicylic acid (SA) plays a central role as a signalling molecule involved in plant defense against microbial attack. Genetic manipulation of SA biosynthesis may therefore help to generate plants that are more disease-resistant. By fusing the two bacterial genes pchA and pchB from Pseudomonas aeruginosa, which encode isochorismate synthase and isochorismate pyruvate-lyase, respectively, we have engineered a novel hybrid enzyme with salicylate synthase (SAS) activity. The pchB-A fusion was expressed in Arabidopsis thaliana under the control of the constitutive cauliflower mosaic virus (CaMV) 35S promoter, with targeting of the gene product either to the cytosol (c-SAS plants) or to the chloroplast (p-SAS plants). In p-SAS plants, the amount of free and conjugated SA was increased more than 20-fold above wild type (WT) level, indicating that SAS is functional in Arabidopsis. P-SAS plants showed a strongly dwarfed phenotype and produced very few seeds. Dwarfism could be caused by the high SA levels per se or, perhaps more likely, by a depletion of the chorismate or isochorismate pools of the chloroplast. Targeting of SAS to the cytosol caused a slight increase in free SA and a significant threefold increase in conjugated SA, probably reflecting limited chorismate availability in this compartment. Although this modest increase in total SA content did not strongly induce the resistance marker PR-1, it resulted nevertheless in enhanced disease resistance towards a virulent isolate of Peronospora parasitica. Increased resistance of c-SAS lines was paralleled with reduced seed production. Taken together, these results illustrate that SAS is a potent tool for the manipulation of SA levels in plants.

Children's experience regarding the quality of their hospital stay: the development of an assessment questionnaire for children

A questionnaire assessing the satisfaction of children with their hospital stay has been developed and tested with 136 children (aged 6-12 years) at 2 Swiss hospital sites. Three out of 4 children were satisfied overall with their hospital stay. Their relationships with the professional medical staff, explanations they received, games they played, and environment, all received positive evaluations. The most critical points were pain, fear, and the absence of relatives. Ninety percent of the children appreciated that their opinions were sought. These results reinforce the importance of having questionnaires available for the children to consider their opinions to enhance the quality of care.

Evolution and sedimentology of a channel fill in the sandy braided South Saskatchewan River and its comparison to the deposits of an adjacent compound bar

The depositional stratigraphy of within-channel deposits in sandy braided rivers is dominated by a variety of barforms (both singular `unit' bars and complex `compound' bars), as well as the infill of individual channels (herein termed `channel fills'). The deposits of bars and channel fills define the key components of facies models for braided rivers and their within-channel heterogeneity, knowledge of which is important for reservoir characterization. However, few studies have sought to address the question of whether the deposits of bars and channel fills can be readily differentiated from each other. This paper presents the first quantitative study to achieve this aim, using aerial images of an evolving modern sandy braided river and geophysical imaging of its subsurface deposits. Aerial photographs taken between 2000 and 2004 document the abandonment and fill of a 1 3 km long, 80 m wide anabranch channel in the sandy braided South Saskatchewan River, Canada. Upstream river regulation traps the majority of very fine sediment and there is little clay (<1%) in the bed sediments. Channel abandonment was initiated by a series of unit bars that stalled and progressively blocked the anabranch entrance, together with dune deposition and stacking at the anabranch entrance and exit. Complete channel abandonment and subsequent fill of up to 3 m of sediment took approximately two years. Thirteen kilometres of ground-penetrating radar surveys, coupled with 18 cores, were obtained over the channel fill and an adjacent 750 m long, 400 m wide, compound bar, enabling a quantitative analysis of the channel and bar deposits. Results show that, in terms of grain-size trends, facies proportions and scale of deposits, there are only subtle differences between the channel fill and bar deposits which, therefore, renders them indistinguishable. Thus, it may be inappropriate to assign different geometric and sedimentological attributes to channel fill and bar facies in object-based models of sandy braided river alluvial architecture.

Shading effects on the yield of an Argentinian wheat cultivar

Shading treatments of 50% of the incident radiation were applied to the semidwarf wheat cultivar Leones INTA before and after anthesis in two field experiments in Argentina in 1987 and 1988. The treatments reduced biological (above-ground dry matter) yield, grain yield and number of grains/m2. Number of grains/m2 was closely and linearly correlated with ear dry weight at anthesis and with the photothermal quotient, calculated from 20 days before to 10 days after anthesis. Grain yield was sink limited, and the shading treatments reduced sink strength. The contribution of preanthesis assimilates to grain yield was smaller in the shaded crops than in the unshaded controls; in unshaded crops, almost 40% of grain yield was contributed by preanthesis assimilates whilst in preanthesis shaded crops this contribution was negligible. The proportion of preanthesis assimilates contributed to the grain was closely related to the decrease in stem dry weight during grain filling. The effects of shading on main stems and tillers were the same.