791 research outputs found

    Implementing implementation science in a randomized controlled trial in Norwegian early childhood education and care

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    The emerging interest in implementation processes in the social, health, and educational sciences has increased the recognition of implementation science. Still, the literature provides limited practical insights on how to successfully develop and conduct interventions within educational settings in randomized controlled trials (RCTs) in line with implementation science. This paper uses the Agder RCT study to provide such insights. We describe how the theory of change and implementation framework supported systematic tailoring and implementation of a new Early Childhood Education and Care (ECEC) intervention. The paper contributes to the emerging use of implementation science in education in general, and more specifically in ECEC. Finally, we discuss how implementation science also needs to be utilized during the upscaling of the project.publishedVersio

    Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions

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    Key contributions to protein structure and stability are provided by weakly polar interactions, which arise from asymmetric electronic distributions within amino acids and peptide bonds. Of particular interest are aromatic side chains whose directional π-systems commonly stabilize protein interiors and interfaces. Here, we consider aromatic-aromatic interactions within a model protein assembly: the dimer interface of insulin. Semi-classical simulations of aromatic-aromatic interactions at this interface suggested that substitution of residue TyrB26 by Trp would preserve native structure while enhancing dimerization (and hence hexamer stability). The crystal structure of a [TrpB26]insulin analog (determined as a T3Rf3 zinc hexamer at a resolution of 2.25 Å) was observed to be essentially identical to that of WT insulin. Remarkably and yet in general accordance with theoretical expectations, spectroscopic studies demonstrated a 150-fold increase in the in vitro lifetime of the variant hexamer, a critical pharmacokinetic parameter influencing design of long-acting formulations. Functional studies in diabetic rats indeed revealed prolonged action following subcutaneous injection. The potency of the TrpB26-modified analog was equal to or greater than an unmodified control. Thus, exploiting a general quantum-chemical feature of protein structure and stability, our results exemplify a mechanism-based approach to the optimization of a therapeutic protein assembly

    Evaluation of the effects of Aegle marmelos and Punica granatum in an experimental model of gastrointestinal barrier dysfunction

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    Background: The study was conducted to evaluate the effects of Aegle marmelos and Punica granatum in an experimental model of gastrointestinal barrier dysfunction induced by common bile duct ligation.Methods: Institutional animal ethics committee approval was obtained. Forty two Wistar rats (either sex, 150-250 gms) divided into seven groups (n=six/group), were subjected to sham operation (group 1) or bile duct ligation (groups 2-7) and treated with distilled water (groups 1 and 2); 0.75mg/kg glutamine (group 3); 0.27 g/kg and 0.54 g/kg of A. marmelos (groups 4 and 5); 3.6 g/kg and 7.2 g/kg P. granatum (groups 6 and 7) orally once daily for 10 days. On Day 11, animals were sacrificed and samples of the jejunum, ileum and mesenteric lymph nodes were obtained to study jejunal and ileal villous morphology, villous heights, jejunal mucosal sucrase enzyme activity and bacterial translocation to mesenteric lymph nodes.Results: Glutamine prevented blunting of the intestinal villi, bacterial translocation and a fall in the sucrase enzyme activity. Both the plant drugs prevented blunting of the villi (except low dose A. marmelos for ileal villi) and a fall in the villous heights (except low dose P. granatum for jejunal villi), decreased the bacterial translocation (except low dose A. marmelos), and prevented a fall in the sucrase enzyme activity when compared to the disease control. The high doses of both A. marmelos and P. granatum were comparable to glutamine for all the variables tested.Conclusions: Both A. marmelos and P. granatum maintained the gastrointestinal barrier function in this model

    Can We Do Away With PTBD?

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    Percutaneous Transhepatic Biliary Drainage (PTBD) is performed in surgical jaundice to decompress the biliary tree and improve hepatic functions. However, the risk of sepsis is high in these patients due to immunosuppression and surgical outcome remains poor. This raises a question—can we do away with PTBD? To answer this query a study was carried out in 4 groups of patients bearing in mind the high incidence of sepsis and our earlier studies, which have demonstrated immunotherapeutic potential of Tinospora cordifolia (TC): (A) those undergoing surgery without PTBD (n = 14), (B) those undergoing surgery after PTBD (n = 13). The mortality was 57.14% in Group A as compared to 61.54% in Group B. Serial estimations of bilirubin levels carried out during the course of drainage (3 Wks) revealed a gradual and significant decrease from 12.52 ± 8.3 mg% to 5.85 ± 3.0 mg%. Antipyrine half-life did not change significantly (18.35 ± 4.2 hrs compared to basal values 21.96 ± 3.78 hrs). The phagocytic and intracellular killing (ICK) capacities of PMN remained suppressed (Basal: 22.13 ± 3.68% phago, and 19.1 ± 4.49% ICK; Post drainage: 20 ± 8.48% Phago and 11.15 ± 3.05% ICK). Thus PTBD did not improve the metabolic capacity ofthe liver and mortality was higher due to sepsis. Group (C) patientg received TC during PTBD (n = 16) and Group (D) patients received TC without PTBD (n = 14). A significant improvement in PMN functions occurred by 3 weeks in both groups (30.29 ± 4.68% phago, 30 ± 4.84% ICK in Group C and 30.4 ± 2.99% phago, 27.15 ± 6.19% ICK in Group D). The mortality in Groups C and D was 25% and 14.2% respectively during the preoperative period. There was no mortality after surgery. It appears from this study that host defenses as reflected by PMN functions play an important role in influencing prognosis. Further decompression of the biliary tree by PTBD seems unwarranted

    Proof firm downsizing and diagnosis-specific disability pensioning in Norway

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    <br>Background: We wanted to investigate if firm downsizing is related to an increased rate of disability pensions among the former employed, especially for those with musculoskeletal and psychiatric diagnoses, and for those having to leave the firm.</br> <br>Methods: Statistics Norway provided a linked file with demographic information and all social security grants from the National Insurance Administration for 1992–2004 for all inhabitants in Norway. Our sample was aged 30–55 years in 1995, being alive, employed and not having a disability pension at the end of 2000. Downsizing was defined as percent change in number of employed per firm from 1995 to end 2000. Employment data were missing for 25.6% of the sample.</br> <br>Results: Disability pension rates in the next four years were 25% higher for those experiencing a 30-59% downsizing than for those not experiencing a reduction of the workforce. 1-29% and 60-100% downsizing did not have this effect. Stayers following down-sizing had higher disability pension rates than leavers. What we have called complex musculoskeletal and psychiatric diagnoses were relatively most common.</br> <br>Conclusion: Moderate downsizing is followed by a significant increase in disability pension rates in the following four years, often with complex musculoskeletal and psychiatric diagnoses.</br&gt

    Celastrus paniculatus and memantine prevent alcohol dependence and improve decision making in alcohol dependent C57BL6 mice

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    Background: Alcohol use disorder poses a huge burden with only a handful of approved drugs. AUD is associated with impaired decision-making that leads to compulsive drinking despite negative consequences. A drug that decreases alcohol consumption as well as improves decision-making may thus prove more useful. This study was planned to evaluate the effect of two drugs, Celastrus paniculatus and memantine on alcohol preference and decision impairment in alcohol-dependent mice. Methods: In part 1, the effect of both the study drugs on alcohol consumption was studied using intermittent access model in 70 male C57BL6 mice. In part 2, effect of drugs on decision making was studied using the rodent version of Iowa gambling task. Mice were divided in seven study groups: Group 1-3: Celastrus paniculatus (140, 280, and 560 mg/kg), Group 4: memantine (25 mg/kg), Group 5: vehicle control 1 (Milk), Group 6: vehicle control 2 (normal saline) and Group 7: naltrexone(1mg/kg). Results: Percentage alcohol preference was lower in test groups i.e., Celastrus paniculatus at medium (40.90±15.18%) and high doses (31.79±7.46%) vs. milk (82.74±8.53%; p<0.05); and in memantine group (36.28±10.99%) vs. normal saline (83.27±5.51%; p<0.05). The results were not significantly different to Naltrexone (19.70±6.90%). Percentage preference to disadvantageous arms was also lower in Celastrus paniculatus, at medium (50.52±1.92%) and high doses (48.11±2.43%) compared to milk (54.47±2.73%; p<0.05) and memantine (47.45±1.67%) compared to normal saline (54.00±2.73%; p<0.05), indicating better decision-making ability in the test groups. The findings were comparable to Naltrexone group (45.43±2.52%). Conclusions: These results indicate that Celastrus paniculatus and memantine reduce alcohol consumption and improve decision making in alcohol-dependent mice

    A study of vitamin B<SUB>12</SUB> protection in experimental liver injury to the rat by carbon tetrachloride

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    Emblica Officinalis: A Novel Therapy for Acute Pancreatitis — An Experimental Study

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    Acute necrotising pancreatitis is associated with an unacceptably high mortality for which no satisfactory remedy exists. Emblica officinalis (E.o.) is a plant prescribed in Ayurveda, the Indian traditional system of medicine, for pancreas-related disorders. This study was carried out to evaluate the protective effect of E.o. against acute necrotising pancreatitis in dogs. Pancreatitis was induced by injecting a mixture of trypsin, bile and blood into the duodenal opening of the pancreatic duct. Twenty eight dogs were divided into 4 groups (n = 6-8 each): GpI–control, GpII–acute pancreatitis, GpIII–sham-operated, GpIV–pretreatment with 28 mg E.o./kg/day for 15 days before inducing pancreatitis. Serum amylase increased from 541.99 ± 129.13 IU/ml to 1592.63 ± 327.83 IU (p<0.02) 2 hrs after the induction of pancreatitis in GpII. The rise in serum amylase in both GpIII and GpIV was not significant. On light microscopic examination, acinar cell damage was less and the total inflammatory score was significantly lower in the E.o. treated group as compared to GpII. Electron microscopy confirmed this and showed an increased amount of smooth, endoplasmic reticulum and small, condensed granules embedded in a vacuole. More studies are needed to explore the clinical potential of E.o. and its mechanism of action
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