119 results on '"Stocker, Claire"'
Search Results
2. Mindfulness practice correlates with reduced exam-induced stress and improved exam performance in preclinical medical students with the “acting with awareness”, “non-judging” and “non-reacting” facets of mindfulness particularly associated with improved exam performance
- Author
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Hearn, Jasmine Heath and Stocker, Claire J.
- Published
- 2022
- Full Text
- View/download PDF
3. Chronic administration of hydrolysed pine nut oil to mice improves insulin sensitivity and glucose tolerance and increases energy expenditure via a free fatty acid receptor 4-dependent mechanism.
- Author
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Wargent, Edward Taynton, Kępczyńska, Małgorzata A., Kaspersen, Mads H., Ulven, Elisabeth Rexen, Arch, Jonathan R. S., Ulven, Trond, and Stocker, Claire Joanne
- Abstract
A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60 % high-fat diet for 3 months. Mice were then dosed hPNO for 24 d, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced body weight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice, but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Developmental programming of appetite and growth in male rats increases hypothalamic serotonin (5-HT)5A receptor expression and sensitivity
- Author
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Wargent, Edward T., Martin-Gronert, Malgorzata S., Cripps, Roselle L., Heisler, Lora K., Yeo, Giles S. H., Ozanne, Susan E., Arch, Jonathan R. S., and Stocker, Claire J.
- Published
- 2020
- Full Text
- View/download PDF
5. The characterisation of porcine endothelial porcine ICAM-1 and P-selectin
- Author
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Stocker, Claire Joanne
- Subjects
572.8 ,Genetics - Published
- 1999
6. Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function
- Author
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Yavari, Arash, Stocker, Claire J., Ghaffari, Sahar, Wargent, Edward T., Steeples, Violetta, Czibik, Gabor, Pinter, Katalin, Bellahcene, Mohamed, Woods, Angela, Martínez de Morentin, Pablo B., Cansell, Céline, Lam, Brian Y.H., Chuster, André, Petkevicius, Kasparas, Nguyen-Tu, Marie-Sophie, Martinez-Sanchez, Aida, Pullen, Timothy J., Oliver, Peter L., Stockenhuber, Alexander, Nguyen, Chinh, Lazdam, Merzaka, O’Dowd, Jacqueline F., Harikumar, Parvathy, Tóth, Mónika, Beall, Craig, Kyriakou, Theodosios, Parnis, Julia, Sarma, Dhruv, Katritsis, George, Wortmann, Diana D.J., Harper, Andrew R., Brown, Laurence A., Willows, Robin, Gandra, Silvia, Poncio, Victor, de Oliveira Figueiredo, Márcio J., Qi, Nathan R., Peirson, Stuart N., McCrimmon, Rory J., Gereben, Balázs, Tretter, László, Fekete, Csaba, Redwood, Charles, Yeo, Giles S.H., Heisler, Lora K., Rutter, Guy A., Smith, Mark A., Withers, Dominic J., Carling, David, Sternick, Eduardo B., Arch, Jonathan R.S., Cawthorne, Michael A., Watkins, Hugh, and Ashrafian, Houman
- Published
- 2016
- Full Text
- View/download PDF
7. Correlates of dermis thickness in mouse models with a range of obesity, insulin resistance and diabetic states
- Author
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Wargent, Edward Taynton, Al-Habian, Amgad, Zaibi, Mohamed Sghaier, Selway, Joanne Louise, Stocker, Claire Joanne, and Langlands, Kenneth
- Subjects
Dermis depth ,obesity ,diabetes ,hyperglycemia ,inflammation - Abstract
Diabetic complications of the skin regarding skin structure have been well documented and researched, notably in relation to wound healing. Recently it has also been discovered that dermis thickness may also be reduced in type 2 diabetic patients. Peripheral damage in diabetes has been attributed to inflammation, as well as hyperglycaemia resulting from insulin resistance. However, this has not been investigated specifically in relation to dermis thickness. This study used mouse models with a range of obesity, insulin resistance and diabetic states to investigate the extent of reduction in dermis thickness that results from these conditions and to elucidate the correlation of dermis thickness with both biomarkers of insulin resistance and whole-body and local proinflammatory cytokine levels, which can both directly damage tissues and be the causative factor of the insulin resistance. The results suggest that the reduced dermis thickness observed in type 2 diabetes is likely a result of hyperglycaemia resulting from insulin resistance rather than the increased proinflammatory milieu resulting from insulin resistance and obesity.
- Published
- 2022
8. Identification of a novel agonist of peroxisome proliferator-activated receptors α and γ that may contribute to the anti-diabetic activity of guggulipid in Lep ob/Lep ob mice
- Author
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Cornick, Claire L., Strongitharm, Barbara H., Sassano, Gary, Rawlins, Christopher, Mayes, Andrew E., Joseph, Alison N., O'Dowd, Jacqueline, Stocker, Claire, Wargent, Ed, Cawthorne, Michael A., Brown, A. Louise, and Arch, Jonathan R.S.
- Published
- 2009
- Full Text
- View/download PDF
9. β2-adrenoceptor agonists can both stimulate and inhibit glucose uptake in mouse soleus muscle through ligand-directed signalling
- Author
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Ngala, Robert A., O’Dowd, Jacqueline F., Stocker, Claire J., Cawthorne, Michael A., and Arch, Jonathan R. S.
- Published
- 2013
- Full Text
- View/download PDF
10. Maternal Obesity and the Fetal Origins of the Metabolic Syndrome
- Author
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Rkhzay-Jaf, Jwan, O’Dowd, Jacqueline F., and Stocker, Claire J.
- Published
- 2012
- Full Text
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11. The influence of leptin on early life programming of obesity
- Author
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Stocker, Claire J. and Cawthorne, Michael A.
- Published
- 2008
- Full Text
- View/download PDF
12. Citation classics in general medical journals: assessing the quality of evidence; a systematic review
- Author
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Ahmad, Suhaib JS., Ahmed, Ahmed R., Kowalewski, Karl Friedrich, Nickel, Felix, Rostami, Kamran, Stocker, Claire J., Hakky, Sherif M., Archid, Rami, McWhinnie, Douglas, Mohajer-Bastami, Ata, Seimenis, Dionysis Skiadopoulos, Ahmad, Sami, Mansour, Sami, Ahmed, Mohamed H., Mital, Dushyant, and Exadaktylos, Aristomenis K.
- Subjects
610 Medicine & health - Abstract
Aim This review provides a comprehensive overview of more than 100 of the most cited studies in general medical journals and evaluates whether citations predict the quality of a scientific article. Background The number of citations is commonly used as a measure of the quality and impact of a scientific article. However, it is often criticised that the number of citations is in fact a poor indicator of the true quality, as it can be influenced by different factors such as current trends. Methods This review was conducted in line with the PRISMA guidelines. The Journal Citation Report (JCR) within Incites allowed the evaluation and comparison of articles, published in general medical journals, using far-reaching citation data drawn from scholarly and technical journals and conference proceedings. All steps of the review were performed in duplicate and conflicts were resolved through consensus. Results The 100 most cited articles published from 1963 until the end of 2018 were identified. The number of citations ranged from 4012 to 31853. Most of the articles were published in the 2000's, followed by the 1990's, 1980's, 1970's and 1960's, respectively. All of the articles were published in five journals. There were 50 studies at level II, 28 at level V, 10 at level IV, 7 at level III, and 5 at Level I. Conclusion This systematic review provides an overview of the most cited articles, published in general medical journals. The number of citations provides an indication of the quality of evidence. However, researchers and clinicians should use standardized assessment tools rather than solely rely on the number of citations in order to judge the quality of published articles.
- Published
- 2020
- Full Text
- View/download PDF
13. Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers
- Author
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Stocker, Claire J., Wargent, Ed, O'Dowd, Jacqueline, Cornick, Claire, Speakman, John R., Arch, Jonathan R.S., and Cawthorne, Michael A.
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Obesity -- Research ,Glucose metabolism -- Research ,Leptin -- Research ,Bioenergetics -- Research ,Energy metabolism -- Research ,Physiological research ,Biological sciences - Abstract
Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg x [kg.sup.-1] x [day.sup.-1]) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring. additional energy balance; energy expenditure doi:10.1152/ajpregu.00676.2006.
- Published
- 2007
14. A novel automated image analysis method for accurate adipocyte quantification
- Author
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Osman, Osman S, Selway, Joanne L, Kępczyńska, Małgorzata A, Stocker, Claire J, OʼDowd, Jacqueline F, Cawthorne, Michael A, Arch, Jonathan RS, Jassim, Sabah, and Langlands, Kenneth
- Published
- 2013
- Full Text
- View/download PDF
15. Editorial: Leptin, obesity and diet at a glance.
- Author
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Hryciw, Deanne H., Stocker, Claire J., Morris, Margaret J., and Caprio, Massimiliano
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LEPTIN ,OBESITY ,DIET ,LEPTIN receptors - Published
- 2022
- Full Text
- View/download PDF
16. Chemerin, a Novel Adipokine in the Regulation of Angiogenesis
- Author
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Bozaoglu, Kiymet, Curran, Joanne E., Stocker, Claire J., Zaibi, Mohamed S., Segal, David, Konstantopoulos, Nicky, Morrison, Shona, Carless, Melanie, Dyer, Thomas D., Cole, Shelley A., Goring, Harald H. H., Moses, Eric K., Walder, Ken, Cawthorne, Michael A., Blangero, John, and Jowett, Jeremy B. M.
- Published
- 2010
17. β2-Adrenoceptors and non-β-adrenoceptors mediate effects of BRL37344 and clenbuterol on glucose uptake in soleus muscle: studies using knockout mice
- Author
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Ngala, Robert A., OʼDowd, Jacqueline, Wang, Steven J., Stocker, Claire, Cawthorne, Michael A., and Arch, Jonathan R.S.
- Published
- 2009
- Full Text
- View/download PDF
18. Peer‐led formative OSCEs: Enhancing learning medicine together.
- Author
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Sharma, Akshara, Hassan‐Smith, Zaki, and Stocker, Claire J.
- Subjects
PEER counseling ,LEARNING strategies ,ACADEMIC achievement ,COST benefit analysis ,PROFESSIONAL competence ,TIME management ,MEDICAL education - Abstract
The article discusses the design and use of a summative-style faculty-led formative Objective Structured Clinical Examinations (fOSCE) in medical school as of 2023. Topics covered include its functions and training coverage for station writing and circuit logistics and tips for providing objective feedback. Also noted is the fOSCE's reduction of administrative time and costs on student organisers and medical school academics.
- Published
- 2023
- Full Text
- View/download PDF
19. Fetal origins of insulin resistance and obesity
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Stocker, Claire J., Arch, Jonathan R. S., and Cawthorne, Michael A.
- Published
- 2005
20. Leanness and Low Plasma Leptin in GPR17 Knockout Mice Are Dependent on Strain and Associated With Increased Energy Intake That Is Not Suppressed by Exogenous Leptin.
- Author
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Wargent, Edward T., Ahmad, Suhaib J. S., Lu, Qing Richard, Kostenis, Evi, Arch, Jonathan R. S., and Stocker, Claire J.
- Subjects
KNOCKOUT mice ,LEPTIN ,HIGH-fat diet ,WHITE adipose tissue ,LEANNESS ,LABORATORY mice - Abstract
Previous studies have shown that agonists of GPR17 stimulate, while antagonists inhibit feeding. However, whole body knockout of GPR17 in mice of the C57Bl/6 strain did not affect energy balance, whereas selective knockout in oligodendrocytes or pro-opiomelanocortin neurons provided protection from high fat diet-induced obesity and impaired glucose homeostasis. We reasoned that whole body knockout of GPR17 in mice of the 129 strain might elicit more marked effects because the 129 strain is more susceptible than the C57Bl/6 strain to increased sympathetic activity and less susceptible to high fat diet-induced obesity. Consistent with this hypothesis, compared to wild-type mice, and when fed on either a chow or a high fat diet, GPR17 -/- mice of the 129 strain displayed increased expression of uncoupling protein-1 in white adipose tissue, lower body weight and fat content, reduced plasma leptin, non-esterified fatty acids and triglycerides, and resistance to high fat diet-induced glucose intolerance. Not only energy expenditure, but also energy intake was raised. Administration of leptin did not suppress the increased food intake in GPR17 -/- mice of the 129 strain, whereas it did suppress food intake in GPR17 +/+ mice. The only difference between GPR17 +/- and GPR17 +/+ mice of the C57Bl/6 strain was that the body weight of the GPR17 -/- mice was lower than that of the GPR17 +/+ mice when the mice were fed on a standard chow diet. We propose that the absence of GPR17 raises sympathetic activity in mice of the 129 strain in response to a low plasma fuel supply, and that the consequent loss of body fat is partly mitigated by increased energy intake. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
21. Endothelial Activation in Monosodium Urate Monohydrate Crystal-induced Inflammation: In Vitro and in Vivo Studies on the Roles of Tumor Necrosis Factor alpha and Interleukin-1
- Author
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Chapman, Peter T., Yarwood, Helen, Harrison, Andrew A., Stocker, Claire J., Jamar, Francois, Gundel, Robert H., Peters, A. Michael, and Haskard, Dorian O.
- Published
- 1997
22. Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation
- Author
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Einerhand Alexandra WC, Wang Steven, O'Dowd Jacqueline, Brown Louise, Mayes Andrew E, Stocker Claire, Sennitt Matthew V, Wargent Ed, Mohede Inge, Arch Jonathan RS, and Cawthorne Michael A
- Subjects
Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays. Results Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lepob/lepob) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity. Conclusions CLA initially decreased but subsequently increased insulin sensitivity in lepob/lepob mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity.
- Published
- 2005
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- View/download PDF
23. High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain.
- Author
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Wargent, Edward T., Kepczynska, Malgorzata, Sghaier Zaibi, Mohamed, Hislop, David C., Arch, Jonathan R. S., and Stocker, Claire J.
- Subjects
WEIGHT gain ,INSULIN resistance ,HIGH-fat diet ,BODY composition ,DUAL-energy X-ray absorptiometry ,CANNABINOID receptors - Abstract
Background. The insulin-sensitizing phytocannabinoid, 1(9)-tetrahydrocannabivarin (THCV) can signal partly via G-protein coupled receptor-55 (GPR55 behaving as either an agonist or an antagonist depending on the assay). The cannabinoid receptor type 1 (CB1R) inverse agonist rimonabant is also a GPR55 agonist under some conditions. Previous studies have shown varied effects of deletion of GPR55 on energy balance and glucose homeostasis in mice. The contribution of signalling via GPR55 to the metabolic effects of THCV and rimonabant has been little studied. Methods. In a preliminary experiment, energy balance and glucose homeostasis were studied in GPR55 knockout and wild-type mice fed on both standard chow (to 20 weeks of age) and high fat diets (from 6 to 15 weeks of age). In the main experiment, all mice were fed on the high fat diet (from 6 to 14 weeks of age). In addition to replicating the preliminary experiment, the effects of once daily administration of THCV (15 mg kg
-1 po) and rimonabant (10 mg kg-1 po) were compared in the two genotypes. Results. There was no effect of genotype on absolute body weight or weight gain, body composition measured by either dual-energy X-ray absorptiometry or Nuclear Mag- netic Resonance (NMR), fat pad weights, food intake, energy expenditure, locomotor activity, glucose tolerance or insulin tolerance in mice fed on chow. When the mice were fed a high fat diet, there was again no effect of genotype on these various aspects of energy balance. However, in both experiments, glucose tolerance was worse in the knockout than the wild-type mice. Genotype did not affect insulin tolerance in either experiment. Weight loss in rimonabant- and THCV-treated mice was lower in knockout than in wild-type mice, but surprisingly there was no detectable effect of genotype on the effects of the drugs on any aspect of glucose homeostasis after taking into account the effect of genotype in vehicle-treated mice. Conclusions. Our two experiments differ from those reported by others in finding impaired glucose tolerance in GPR55 knockout mice in the absence of any effect on body weight, body composition, locomotor activity or energy expenditure. Nor could we detect any effect of genotype on insulin tolerance, so the possibility that GPR55 regulates glucose-stimulated insulin secretion merits further investigation. By contrast with the genotype effect in untreated mice, we found that THCV and rimonabant reduced weight gain, and this effect was in part mediated by GPR55. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
24. A systematic review and taxonomy of tools for evaluating evidence-based medicine teaching in medical education.
- Author
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Kumaravel, Bharathy, Hearn, Jasmine Heath, Jahangiri, Leila, Pollard, Rachel, Stocker, Claire J., and Nunan, David
- Subjects
EVIDENCE-based medicine ,META-analysis ,MEDICAL education ,MEDICAL teaching personnel ,TAXONOMY - Abstract
Background: The importance of teaching the skills and practice of evidence-based medicine (EBM) for medical professionals has steadily grown in recent years. Alongside this growth is a need to evaluate the effectiveness of EBM curriculum as assessed by competency in the five 'A's': asking, acquiring, appraising, applying and assessing (impact and performance). EBM educators in medical education will benefit from a compendium of existing assessment tools for assessing EBM competencies in their settings. The purpose of this review is to provide a systematic review and taxonomy of validated tools that evaluate EBM teaching in medical education. Methods: We searched MEDLINE, EMBASE, Cochrane library, Educational Resources Information Centre (ERIC), Best Evidence Medical Education (BEME) databases and references of retrieved articles published between January 2005 and March 2019. We have presented the identified tools along with their psychometric properties including validity, reliability and relevance to the five domains of EBM practice and dimensions of EBM learning. We also assessed the quality of the tools to identify high quality tools as those supported by established interrater reliability (if applicable), objective (non-self-reported) outcome measures and achieved ≥ 3 types of established validity evidence. We have reported our study in accordance with the PRISMA guidelines. Results: We identified 1719 potentially relevant articles of which 63 full text articles were assessed for eligibility against inclusion and exclusion criteria. Twelve articles each with a unique and newly identified tool were included in the final analysis. Of the twelve tools, all of them assessed the third step of EBM practice (appraise) and four assessed just that one step. None of the twelve tools assessed the last step of EBM practice (assess). Of the seven domains of EBM learning, ten tools assessed knowledge gain, nine assessed skills and-one assessed attitude. None addressed reaction to EBM teaching, self-efficacy, behaviours or patient benefit. Of the twelve tools identified, six were high quality. We have also provided a taxonomy of tools using the CREATE framework, for EBM teachers in medical education. Conclusions: Six tools of reasonable validity are available for evaluating most steps of EBM and some domains of EBM learning. Further development and validation of tools that evaluate all the steps in EBM and all educational outcome domains are needed. Systematic review registration: PROSPERO CRD42018116203. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
25. Citation classics in general medical journals: assessing the quality of evidence; a systematic review.
- Author
-
Ahmad, Suhaib J. S., Ahmed, Ahmed R., Kowalewski, Karl Friedrich, Nickel, Felix, Rostami, Kamran, Stocker, Claire J., Hakky, Sherif M., Archid, Rami, McWhinnie, Douglas, Mohajer-Bastami, Ata, Seimenis, Dionysis Skiadopoulos, Ahmad, Sami, Mansour, Sami, Ahmed, Mohamed H., Mital, Dushyant, and Exadaktylos, Aristomenis K.
- Subjects
ELECTRONIC journals ,FAMILY medicine ,SYSTEMATIC reviews ,EVIDENCE-based medicine ,DATA quality - Abstract
Aim: This review provides a comprehensive overview of more than 100 of the most cited studies in general medical journals and evaluates whether citations predict the quality of a scientific article. Background: The number of citations is commonly used as a measure of the quality and impact of a scientific article. However, it is often criticised that the number of citations is in fact a poor indicator of the true quality, as it can be influenced by different factors such as current trends. Methods: This review was conducted in line with the PRISMA guidelines. The Journal Citation Report (JCR) within Incites allowed the evaluation and comparison of articles, published in general medical journals, using far-reaching citation data drawn from scholarly and technical journals and conference proceedings. All steps of the review were performed in duplicate and conflicts were resolved through consensus. Results: The 100 most cited articles published from 1963 until the end of 2018 were identified. The number of citations ranged from 4012 to 31853. Most of the articles were published in the 2000's, followed by the 1990's, 1980's, 1970's and 1960's, respectively. All of the articles were published in five journals. There were 50 studies at level II, 28 at level V, 10 at level IV, 7 at level III, and 5 at Level I. Conclusion: This systematic review provides an overview of the most cited articles, published in general medical journals. The number of citations provides an indication of the quality of evidence. However, researchers and clinicians should use standardized assessment tools rather than solely rely on the number of citations in order to judge the quality of published articles. [ABSTRACT FROM AUTHOR]
- Published
- 2020
26. The effects of sarcolipin over-expression in mouse skeletal muscle on metabolic activity
- Author
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Butler, John, Smyth, Neil, Broadbridge, Robert, Council, Claire E., Lee, Anthony G., Stocker, Claire J., Hislop, David C., Arch, Jonathan R.S., Cawthorne, Michael A., and Malcolm East, J.
- Subjects
Sarcolipin ,SERCA ,High fat diet ,Biophysics ,Thermogenesis ,Energy expenditure ,Obesity ,Biochemistry ,Molecular Biology - Abstract
Studies in sarcolipin knockout mice have led to the suggestion that skeletal muscle sarcolipin plays a role in thermogenesis. The mechanism proposed is uncoupling of the sarcoplasmic reticulum calcium pump. However, in other work sarcolipin was not detected in mouse skeletal tissue. We have therefore measured sarcolipin levels in mouse skeletal muscle using semi-quantitative western blotting and synthetic mouse sarcolipin. Sarcolipin levels were so low that it is unlikely that knocking out sarcolipin would have a measurable effect on thermogenesis by SERCA. In addition, overexpression of neither wild type nor FLAG-tagged variants of mouse sarcolipin in transgenic mice had any major significant effects on body mass, energy expenditure, even when mice were fed on a high fat diet.
- Published
- 2015
27. Patient-centered medical education: A proposed definition.
- Author
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Hearn, Jasmine, Dewji, Mohamed, Stocker, Claire, and Simons, Greg
- Subjects
MEDICAL school faculty ,MEDICAL education ,NEEDS assessment ,SYSTEMATIC reviews ,PSYCHOSOCIAL factors ,TEACHING methods ,PATIENT-centered care ,CLINICAL education ,PATIENTS' attitudes - Abstract
Multiple papers have been presented to define patient-centered care, with regulatory bodies such as the General Medical Council mapping this in their professional standards. Educational institutions clearly value instilling appreciation of patient-centredness in medical training, and attempts have been made to make medical education more patient-centered in practice. Such attempts are often limited to expert patients sharing personal stories, and public involvement in teaching. Despite the drive towards patient-centered care and medical education, there has been no attempt to formally define what patient-centered medical education is and what it means to medical educators globally. This paper proposes a definition of patient-centered medical education that is about the patients, with the patients, and for the patients, to ensure current and future doctors remain sensitive to all of the needs of the people they care for. This should be considered at both the micro and macro community levels. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
28. Gallbladder perforation into the greater omentum following sleeve gastrectomy: A case report study
- Author
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Ahmad, Suhaib J.S., Hakky, Sherif M., McWhinnie, Douglas, Stocker, Claire J., Thomas, Peter, and Ahmad, Sami
- Published
- 2018
- Full Text
- View/download PDF
29. Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation
- Author
-
Wargent, Ed, Sennitt, Matthew V, Stocker, Claire, Mayes, Andrew E, Brown, Louise, O'Dowd, Jacqueline, Wang, Steven, Einerhand, Alexandra WC, Mohede, Inge, Arch, Jonathan RS, and Cawthorne, Michael A
- Subjects
Blood Glucose ,Biometry ,Time Factors ,integumentary system ,Tumor Necrosis Factor-alpha ,Research ,Body Weight ,Peroxisome Proliferator-Activated Receptors ,Mice, Obese ,food and beverages ,Cell Line ,Mice, Inbred C57BL ,Mice ,lcsh:Nutritional diseases. Deficiency diseases ,Chlorocebus aethiops ,Animals ,Humans ,Insulin ,Female ,Linoleic Acids, Conjugated ,lipids (amino acids, peptides, and proteins) ,Adiponectin ,lcsh:RC620-627 ,Triglycerides - Abstract
Background Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays. Results Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lepob/lepob) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity. Conclusions CLA initially decreased but subsequently increased insulin sensitivity in lepob/lepob mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity.
- Published
- 2005
30. Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity.
- Author
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Azevedo, Carlos M. G., Watterson, Kenneth R., Wargent, Ed T., Hansen, Steffen V. F., Hudson, Brian D., Kępczyńska, Małgorzata A., Dunlop, Julia, Shimpukade, Bharat, Christiansen, Elisabeth, Milligan, Graeme, Stocker, Claire J., and Ulven, Trond
- Published
- 2016
- Full Text
- View/download PDF
31. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids
- Author
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Zaibi, Mohamed S., Stocker, Claire J., O’Dowd, Jacqueline, Davies, Alison, Bellahcene, Mohamed, Cawthorne, Michael A., Brown, Alastair J.H., Smith, David M., and Arch, Jonathan R.S.
- Published
- 2010
- Full Text
- View/download PDF
32. Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area, and Robust in Vivo Efficacy.
- Author
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Hansen, Steffen V. F., Christiansen, Elisabeth, Urban, Christian, Hudson, Brian D., Stocker, Claire J., Due-Hansen, Maria E., Wargent, Ed T., Shimpukade, Bharat, Almeida, Reinaldo, Ejsing, Christer S., Cawthorne, Michael A., Kassack, Matthias U., Milligan, Graeme, and Ulven, Trond
- Published
- 2016
- Full Text
- View/download PDF
33. Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases.
- Author
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Christiansen, Elisabeth, Watterson, Kenneth R., Stocker, Claire J., Sokol, Elena, Jenkins, Laura, Simon, Katharina, Grundmann, Manuel, Petersen, Rasmus K., Wargent, Edward T., Hudson, Brian D., Kostenis, Evi, Ejsing, Christer S., Cawthorne, Michael A., Milligan, Graeme, and Ulven, Trond
- Subjects
BLOOD sugar analysis ,METABOLIC disorder treatment ,ANALYSIS of variance ,ANIMAL experimentation ,CELL culture ,FATTY acids ,GLUCOSE tolerance tests ,MICE ,PROBABILITY theory ,RESEARCH funding ,T-test (Statistics) ,DATA analysis software ,PEROXISOME proliferator-activated receptors ,THERAPEUTICS - Abstract
Various foods are associated with effects against metabolic diseases such as insulin resistance and type 2 diabetes; however, their mechanisms of action are mostly unclear. Fatty acids may contribute by acting as precursors of signalling molecules or by direct activity on receptors. The medium- and long-chain NEFA receptor FFA1 (free fatty acid receptor 1, previously known as GPR40) has been linked to enhancement of glucose-stimulated insulin secretion, whereas FFA4 (free fatty acid receptor 4, previously known as GPR120) has been associated with insulin-sensitising and anti-inflammatory effects, and both receptors are reported to protect pancreatic islets and promote secretion of appetite and glucose-regulating hormones. Hypothesising that FFA1 and FFA4 mediate therapeutic effects of dietary components, we screened a broad selection of NEFA on FFA1 and FFA4 and characterised active compounds in concentration–response curves. Of the screened compounds, pinolenic acid, a constituent of pine nut oil, was identified as a relatively potent and efficacious dual FFA1/FFA4 agonist, and its suitability for further studies was confirmed by additional in vitro characterisation. Pine nut oil and free and esterified pure pinolenic acid were tested in an acute glucose tolerance test in mice. Pine nut oil showed a moderately but significantly improved glucose tolerance compared with maize oil. Pure pinolenic acid or ethyl ester gave robust and highly significant improvements of glucose tolerance. In conclusion, the present results indicate that pinolenic acid is a comparatively potent and efficacious dual FFA1/FFA4 agonist that exerts antidiabetic effects in an acute mouse model. The compound thus deserves attention as a potential active dietary ingredient to prevent or counteract metabolic diseases. [ABSTRACT FROM PUBLISHER]
- Published
- 2015
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- View/download PDF
34. Histochemical and immunohistochemical evaluation of mouse skin histology: comparison of fixation with neutral buffered formalin and alcoholic formalin.
- Author
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Al-Habian, Amgad, Harikumar, Parvathy E., Stocker, Claire J., Langlands, Kenneth, and Selway, Joanne L.
- Published
- 2014
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- View/download PDF
35. A novel method to assess collagen architecture in skin.
- Author
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Osman, Osman S., Selway, Joanne L., Harikumar, Parvathy E., Stocker, Claire J., Wargent, Edward T., Cawthorne, Michael A., Jassim, Sabah, and Langlands, Kenneth
- Subjects
COLLAGEN ,BIOLOGICAL specimens ,SKIN ,FIBROSIS ,FOURIER transform spectroscopy ,IMAGING systems in biology - Abstract
Background: Texture within biological specimens may reveal critical insights, while being very difficult to quantify. This is a particular problem in histological analysis. For example, cross-polar images of picrosirius stained skin reveal exquisite structure, allowing changes in the basketweave conformation of healthy collagen to be assessed. Existing techniques measure gross pathological changes, such as fibrosis, but are not sufficiently sensitive to detect more subtle and progressive pathological changes in the dermis, such as those seen in ageing. Moreover, screening methods for cutaneous therapeutics require accurate, unsupervised and high-throughput image analysis techniques. Results: By analyzing spectra of images post Gabor filtering and Fast Fourier Transform, we were able to measure subtle changes in collagen fibre orientation intractable to existing techniques. We detected the progressive loss of collagen basketweave structure in a series of chronologically aged skin samples, as well as in skin derived from a model of type 2 diabetes mellitus. Conclusions: We describe a novel bioimaging approach with implications for the evaluation of pathology in a broader range of biological situations. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
36. Endocrine pancreatic development: impact of obesity and diet.
- Author
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O'Dowd, Jacqueline F. and Stocker, Claire J.
- Subjects
ISLANDS of Langerhans ,ENDOCRINE glands ,OBESITY ,BODY weight ,DIET - Abstract
During embryonic development, multipotent endodermal cells differentiate to form the pancreas. Islet cell clusters arising from the pancreatic bud form the acini tissue and exocrine ducts whilst pancreatic islets form around the edges of the clusters. The successive steps of islet differentiation are controlled by a complex network of transcription factors and signals that influence cell differentiation, growth and lineage. A Westernized lifestyle has led to an increased consumption of a high saturated fat diet, and an increase in maternal obesity. The developing fetus is highly sensitive to the intrauterine environment, therefore any alteration in maternal nutrition during gestation and lactation which affects the in-utero environment during the key developmental phases of the pancreas may change the factors controlling β-cell development and β-cell mass. Whilst the molecular mechanisms behind the adaptive programming of β-cells are still poorly understood it is established that changes arising from maternal obesity and/or over-nutrition may affect the ability to maintain fetal β-cell mass resulting in an increased risk of type 2 diabetes in adulthood. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
37. Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content.
- Author
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Bellahcene, Mohamed, O'dowd, Jacqueline F., Wargent, Ed T., Zaibi, Mohamed S., Hislop, David C., Ngala, Robert A., Smith, David M., Cawthorne, Michael A., Stocker, Claire J., and Arch, Jonathan R. S.
- Subjects
CELL receptors ,ADIPOSE tissues ,ANALYSIS of variance ,ANIMAL experimentation ,BLOOD sugar ,BODY composition ,CALORIMETRY ,CELLULAR signal transduction ,CHOLESTEROL ,ENERGY metabolism ,FATTY acids ,FISHER exact test ,GENE expression ,GENES ,GLUCOSE tolerance tests ,HIGH density lipoproteins ,INSULIN ,MICE ,POLYMERASE chain reaction ,RESEARCH funding ,TRIGLYCERIDES ,X-ray densitometry in medicine ,LEPTIN ,REPEATED measures design ,DATA analysis software ,CELL physiology - Abstract
SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation of the Gαi-protein-coupled receptor GPR41 by SCFA in β-cells and sympathetic ganglia inhibits insulin secretion and increases sympathetic outflow, respectively. A possible role in stimulating leptin secretion by adipocytes is disputed. In the present study, we investigated energy balance and glucose homoeostasis in GPR41 knockout mice fed on a standard low-fat or a high-fat diet. When fed on the low-fat diet, body fat mass was raised and glucose tolerance was impaired in male but not female knockout mice compared to wild-type mice. Soleus muscle and heart weights were reduced in the male mice, but total body lean mass was unchanged. When fed on the high-fat diet, body fat mass was raised in male but not female GPR41 knockout mice, but by no more in the males than when they were fed on the low-fat diet. Body lean mass and energy expenditure were reduced in male mice but not in female knockout mice. These results suggest that the absence of GPR41 increases body fat content in male mice. Gut-derived SCFA may raise energy expenditure and help to protect against obesity by activating GPR41. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
- Full Text
- View/download PDF
38. Contrasts between the effects of zinc-α2-glycoprotein, a putative β3/2-adrenoceptor agonist and the β3/2-adrenoceptor agonist BRL35135 in C57Bl/6 (ob/ob) mice.
- Author
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Wargent, Edward T., O'Dowd, Jacqueline F., Zaibi, Mohamed S., Gao, Dan, Chen Bing, Trayhurn, Paul, Cawthorne, Michael A., Arch, Jonathan R. S., and Stocker, Claire J.
- Subjects
ADIPOSE tissues ,BLOOD lipids ,MESSENGER RNA ,GLUCOSE ,GLYCOPROTEINS ,ZINC ,HOMEOSTASIS - Abstract
Previous studies by Tisdale et al. have reported that zinc-α
2 -glycoprotein (ZAG (AZGP1)) reduces body fat content and improves glucose homeostasis and the plasma lipid profile in Aston (ob/ob) mice. It has been suggested that this might be mediated via agonism of β3 - and possibly β2 -adrenoceptors. We compared the effects of dosing recombinant human ZAG (100 mg, i.v.) and BRL35135 (0.5 mg/kg, i.p.), which is in rodents a 20-fold selective β3 - relative to β2 -adrenoceptor agonist, given once daily for 10 days to male C57Bl/6 Lepob/Lepob mice. ZAG, but not BRL35135, reduced food intake. BRL35135, but not ZAG, increased energy expenditure acutely and after sub-chronic administration. Only BRL35135 increased plasma concentrations of glycerol and non-esterified fatty acid. Sub-chronic treatment with both ZAG and BRL35135 reduced fasting blood glucose and improved glucose tolerance, but the plasma insulin concentration 30 min after administration of glucose was lowered only by BRL35135. Both ZAG and BRL35135 reduced b1-adrenoceptor mRNA levels in white adipose tissue, but only BRL35135 reduced β2 -adrenoceptor mRNA. Both ZAG and BRL35135 reduced β1 -adrenoceptor mRNA levels in brown adipose tissue, but neither influenced β2 -adrenoceptor mRNA, and only BRL35135 increased β3 -adrenoceptor and uncoupling protein-1 (UCP1) mRNA levels in brown adipose tissue. Thus, ZAG and BRL35135 had similar effects on glycaemic control and shared some effects on b-adrenoceptor gene expression in adipose tissue, but ZAG did not display the thermogenic effects of the β-adrenoceptor agonist, nor did it increase β3 -adrenoceptor or UCP1 gene expression in brown adipose tissue. ZAG does not behave as a typical β3/2 -adrenoceptor agonist. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
39. Beta2-adrenoceptors and non-beta-adrenoceptors mediate effects of BRL37344 and clenbuterol on glucose uptake in soleus muscle: studies using knockout mice.
- Author
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Ngala, Robert A., O'Dowd, Jacqueline, Wang, Steven J., Stocker, Claire, Cawthorne, Michael A., and Arch, Jonathan R.S.
- Subjects
ADRENERGIC receptors ,CLENBUTEROL ,GLUCOSE ,SKELETAL muscle ,LABORATORY mice ,LIGANDS (Biochemistry) ,GLUCOSE metabolism ,ADRENERGIC beta agonists ,ADRENERGIC beta blockers ,ANIMAL experimentation ,CELLULAR signal transduction ,COMPARATIVE studies ,DOSE-effect relationship in pharmacology ,ETHANOLAMINES ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,RESEARCH ,EVALUATION research ,PHARMACODYNAMICS - Abstract
Background and Purpose: In previous work, 10 pM BRL37344 and 10 pM clenbuterol stimulated glucose uptake in mouse soleus muscle. Ten nM BRL37344 also stimulated uptake but 100 nM clenbuterol inhibited uptake. Antagonist studies suggested that the opposite effects of 10 nM BRL37344 and 100 nM clenbuterol are mediated by the beta(2)-adrenoceptor. BRL37344 and clenbuterol have been studied in muscles that lack beta(3)-, beta(2)- or all three beta-adrenoceptors. Effects of beta-adrenoceptor antagonists on responses to the agonists have been studied further using muscles from wild-type mice.Experimental Approach: Soleus muscles of wild-type or beta-adrenoceptor knockout mice were incubated with 2-deoxy[1-(14)C]-glucose, and beta-adrenoceptor ligands. Formation of 2-deoxy[1-(14)C]-glucose-6-phosphate was measured.Key Results: Concentration-response relationships were similar for BRL37344 and clenbuterol in normal muscle and muscle lacking beta(3)-adrenoceptors. Ten pM BRL37344 and clenbuterol stimulated glucose uptake in muscle lacking beta(2)-adrenoceptors or all three beta-adrenoceptors, but 10 nM BRL37344 did not stimulate uptake in either case, and 100 nM clenbuterol stimulated, rather than inhibited, uptake in muscle lacking beta(2)-adrenoceptors. One hundred nM clenbuterol also stimulated glucose uptake in normal muscle when beta(2)-adrenoceptors were blocked with ICI118551, and this was not prevented by antagonism of beta(1)- or beta(3)-adrenoceptors.Conclusions and Implications: Ten nM BRL37344 and 100 nM clenbuterol have opposite effects on glucose uptake but both effects are mediated by the beta(2)-adrenoceptor - apparently an example of agonist-directed signalling. Ten pM BRL37344, 10 pM clenbuterol and 100 nM clenbuterol in the presence of ICI118551 stimulate glucose uptake via beta-adrenoceptor-independent mechanisms, demonstrating unknown properties for the agonists. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
40. CLONING OF PORCINE INTERCELLULAR ADHESION MOLECULE-1 AND CHARACTERIZATION OF ITS INDUCTION ON ENDOTHELIAL CELLS BY CYTOKINES1.
- Author
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Stocker, Claire J., Sugars, Katharine L., Yarwood, Helen, Delikouras, Alex, Lechler, Robert I., Dorling, Anthony, Landis, R. Clive, Morley, Bernard J., and Haskard, Dorian O.
- Published
- 2000
- Full Text
- View/download PDF
41. Evaluation of Clinical Factors Predictive of Diabetes Remission Following Bariatric Surgery.
- Author
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Mateo-Gavira, Isabel, Sánchez-Toscano, Esteban, Mayo-Ossorio, Mª Ángeles, Pacheco-García, José Manuel, Prada-Oliveira, Jose Arturo, Vílchez-López, Francisco Javier, and Stocker, Claire J.
- Subjects
BARIATRIC surgery ,TYPE 2 diabetes ,BODY mass index ,DISEASE remission - Abstract
Bariatric surgery is an effective treatment for achieving significant weight loss and improving metabolic comorbidities such as type 2 diabetes mellitus (T2DM). The aim of our study was to investigate clinical factors related to T2DM remission in obese patients who had undergone bariatric surgery. Methods: A cohort of patients with T2DM and a minimum of class II obesity undergoing bariatric surgery had their clinical and anthropometric variables assessed. The statistical evaluation included multivariate analyses of clinical factors predicting a T2DM remission two years post-surgery. Results: 83 patients were included (mean age 44.13 ± 10.38 years). Two years post-surgery, the percentage of excess weight lost was 63.43 ± 18.59%, and T2DM was resolved in 79.5% of the patients. T2DM remission was directly related to a high body mass index (BMI) (OR: 1.886; p = 0.022) and the absence of macro-vascular complications (OR: 34.667; p = 0.002), while it was inversely associated with T2DM with a duration longer than 5 years (OR: 0.022; p = 0.040) and baseline insulin treatment (OR: 0.001; p = 0.009). 15.6% of the patients presented early complications and 20.5% developed late complications. Conclusion: In our study sample, bariatric surgery proved to be an effective and safe technique for sustained medium-term weight loss and the resolution of T2DM. A higher baseline BMI, a shorter T2DM duration, non-insulin treatment, and the absence of macro-vascular complications are factors predictive of T2DM remission. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. IN VITRO ACCOMMODATION OF IMMORTALIZED PORCINE ENDOTHELIAL CELLS.
- Author
-
Dorling, Anthony, Stocker, Claire, Tsao, Twee, Haskard, Dorian O., and Lechler, Robert I.
- Published
- 1996
- Full Text
- View/download PDF
43. Endothelial activation in monosodium urate monohydrate crystal-induced inflammation. In vitro and in vivo studies on the roles of tumor necrosis factor α and interleukin-1.
- Author
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Chapman, Peter T., Yarwood, Helen, Harrison, Andrew A., Stocker, Claire J., Jamar, François, Gundel, Robert H., Peters, A. Michael, and Haskard, Dorian O.
- Published
- 1997
- Full Text
- View/download PDF
44. Identification of a novel agonist of peroxisome proliferator-activated receptors α and γ that may contribute to the anti-diabetic activity of guggulipid in Lepob/Lepob mice
- Author
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Cornick, Claire L., Strongitharm, Barbara H., Sassano, Gary, Rawlins, Christopher, Mayes, Andrew E., Joseph, Alison N., O'Dowd, Jacqueline, Stocker, Claire, Wargent, Ed, Cawthorne, Michael A., Brown, A. Louise, and Arch, Jonathan R.S.
- Subjects
- *
NUCLEAR receptors (Biochemistry) , *HYPOGLYCEMIC agents , *PLANT cell microbodies , *COMMIPHORA wightii , *LABORATORY mice , *PLANT extracts , *LIPID metabolism disorders , *OBESITY in animals , *VETERINARY therapeutics , *THERAPEUTICS - Abstract
Abstract: The ethyl acetate extract of the gum of the guggul tree, Commiphora mukul (guggulipid), is marketed for the treatment of dyslipidaemia and obesity. We have found that it protects Lepob/Lepob mice from diabetes and have investigated possible molecular mechanisms for its metabolic effects, in particular those due to a newly identified component, commipheric acid. Both guggulipid (EC50=0.82 μg/ml) and commipheric acid (EC50=0.26 μg/ml) activated human peroxisome proliferator-activated receptor α (PPARα) in COS-7 cells transiently transfected with the receptor and a reporter gene construct. Similarly, both guggulipid (EC50=2.3 μg/ml) and commipheric acid (EC50=0.3 μg/ml) activated PPARγ and both promoted the differentiation of 3T3 L1 preadipocytes to adipocytes. Guggulipid (EC50=0.66 μg/ml), but not commipheric acid, activated liver X receptor α (LXRα). E- and Z-guggulsterones, which are largely responsible for guggulipid''s hypocholesterolaemic effect, had no effects in these assays. Guggulipid (20 g/kg diet) improved glucose tolerance in female Lepob/Lepob mice. Pure commipheric acid, given orally (960 mg/kg body weight, once daily), increased liver weight but did not affect body weight or glucose tolerance. However, the ethyl ester of commipheric acid (150 mg/kg, twice daily) lowered fasting blood glucose and plasma insulin, and plasma triglycerides without affecting food intake or body weight. These results raise the possibility that guggulipid has anti-diabetic activity due partly to commipheric acid''s PPARα/γ agonism, but the systemic bioavailability of orally dosed, pure commipheric acid appears poor. Another component may contribute to guggulipid''s anti-diabetic and hypocholesterolaemic activity by stimulating LXRα. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
45. Successful instillation of professionalism in our future doctors.
- Author
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Wargent E and Stocker C
- Abstract
This article was migrated. The article was marked as recommended. Dynamic approaches are required in teaching professionalism to medical students. Awareness of this issue has both arisen from and generated by a dramatic increase in publications relating to professionalism teaching in medical education. This report explores the current state of defining professionalism and shows that current literature reveals a strong proclivity to adopting "Communities of Practice" as the learning paradigm most likely to successfully instil professional values. This pedagogy is then critiqued with regards to the requirement of an undergraduate curriculum with the conclusion that Communities of Practice should be pertinent to successfully empowering medical students' professionalism., (Copyright: © 2021 Wargent E and Stocker C.)
- Published
- 2021
- Full Text
- View/download PDF
46. Metabolic and energetic benefits of microRNA-22 inhibition.
- Author
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Thibonnier M, Esau C, Ghosh S, Wargent E, and Stocker C
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Obesity drug therapy, Obesity genetics, Diabetes Mellitus, Type 2, Insulin Resistance genetics, MicroRNAs genetics
- Abstract
Introduction: We previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet-induced obesity that specific microRNA-22-3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such as KDM3A , KDM6B , PPARA , PPARGC1B and SIRT1 involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis., Research Design and Methods: We now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22-3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Body composition, various blood parameters and energy expenditure were measured at several timepoints between week 12 and week 27 of age., Results: Weekly subcutaneous injections of APT-110 for 12 weeks produced a sustained increase of energy expenditure as early as day 11 of treatment, a significant fat mass reduction, but no change of appetite nor physical activity. Insulin sensitivity as well as circulating glucose, cholesterol and leptin were improved. There was a dramatic reduction of liver steatosis after 3 months of active treatment. RNA sequencing revealed an activation of lipid metabolism pathways in a tissue-specific manner., Conclusions: These original findings suggest that microRNA-22-3p inhibition could lead to a potent treatment of fat accumulation, insulin resistance, and related complex metabolic disorders such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease., Competing Interests: Competing interests: Ownership: MT is the founder and a shareholder of AptamiR Therapeutics. Intellectual property: MT is the inventor of several patents assigned to AptamiR Therapeutics., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
- Full Text
- View/download PDF
47. Isolation and Purification of Rodent Pancreatic Islets of Langerhans.
- Author
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O'Dowd JF and Stocker CJ
- Subjects
- Animals, Cell Culture Techniques, Collagenases, Islets of Langerhans Transplantation, Tissue Culture Techniques, Cell Separation methods, Islets of Langerhans cytology, Rodentia
- Abstract
This chapter describes the detailed protocol for the isolation and purification of islets of Langerhans from rodent pancreas using collagenase digestion. The first step of the process is to separate and isolate the insulin-producing islets of Langerhans from the rest of the pancreas. The pancreas is excised from the animal, trimmed of nonpancreatic tissues before being inflated and chopped into small pieces. The connective tissue is then broken down with a collagenase enzyme solution to selectively digest the bulk of the exocrine tissue while leaving the endocrine islets intact and separated from their surrounding non-islet tissue. Once this process is completed, the islets of Langerhans are separated from the remaining mixture by centrifugation and purified by the means of hand picking. Once isolated, the subsequent islets can be used for several varied experimental processes, including transplantation, the study of pathophysiological mechanisms in diabetic conditions, and in the screening of novel therapeutic approaches in pharmacological research.
- Published
- 2020
- Full Text
- View/download PDF
48. Schwartz rounds in undergraduate medical education facilitates active reflection and individual identification of learning need.
- Author
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Stocker C, Cooney A, Thomas P, Kumaravel B, Langlands K, and Hearn J
- Abstract
This article was migrated. The article was marked as recommended. Strategies applying Schwartz Rounds to improve wellbeing of medical students has focused on the clinical years of study. This pilot study investigates whether Schwartz Rounds could be effective in developing students' reflective practice in Year 2 undergraduates. Engagement with the Schwartz Round was high with over 50% of the students identifying learning needs through reflection on the Round. Schwartz Rounds promoted recognition of the value of reflective practice and increased self-awareness of student needs., (Copyright: © 2018 Stocker C et al.)
- Published
- 2018
- Full Text
- View/download PDF
49. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.
- Author
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Martin-Gronert MS, Stocker CJ, Wargent ET, Cripps RL, Garfield AS, Jovanovic Z, D'Agostino G, Yeo GS, Cawthorne MA, Arch JR, Heisler LK, and Ozanne SE
- Subjects
- Animals, Animals, Newborn, Arcuate Nucleus of Hypothalamus drug effects, Arcuate Nucleus of Hypothalamus metabolism, Body Weight drug effects, Dietary Proteins pharmacology, Feeding Behavior drug effects, Female, Fenfluramine administration & dosage, Fenfluramine pharmacology, Fetus drug effects, Fetus metabolism, Hypothalamus anatomy & histology, Hypothalamus drug effects, Hypothalamus growth & development, Laser Capture Microdissection, Male, Neurons metabolism, Oligonucleotide Array Sequence Analysis, Organ Size drug effects, Pregnancy, Rats, Wistar, Reproducibility of Results, Serotonin metabolism, Time Factors, Tryptophan metabolism, Growth and Development drug effects, Hypothalamus metabolism, Receptor, Serotonin, 5-HT2A metabolism, Receptor, Serotonin, 5-HT2C metabolism
- Abstract
Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist., (© 2016. Published by The Company of Biologists Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
50. The effects of sarcolipin over-expression in mouse skeletal muscle on metabolic activity.
- Author
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Butler J, Smyth N, Broadbridge R, Council CE, Lee AG, Stocker CJ, Hislop DC, Arch JR, Cawthorne MA, and Malcolm East J
- Subjects
- Animals, Body Weight genetics, Body Weight physiology, Diet, High-Fat, Energy Metabolism genetics, Energy Metabolism physiology, Male, Mice, Mice, Transgenic, Oligopeptides genetics, Oligopeptides metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism, Thermogenesis genetics, Thermogenesis physiology, Up-Regulation, Muscle Proteins genetics, Muscle Proteins metabolism, Muscle, Skeletal metabolism, Proteolipids genetics, Proteolipids metabolism
- Abstract
Studies in sarcolipin knockout mice have led to the suggestion that skeletal muscle sarcolipin plays a role in thermogenesis. The mechanism proposed is uncoupling of the sarcoplasmic reticulum calcium pump. However, in other work sarcolipin was not detected in mouse skeletal tissue. We have therefore measured sarcolipin levels in mouse skeletal muscle using semi-quantitative western blotting and synthetic mouse sarcolipin. Sarcolipin levels were so low that it is unlikely that knocking out sarcolipin would have a measurable effect on thermogenesis by SERCA. In addition, overexpression of neither wild type nor FLAG-tagged variants of mouse sarcolipin in transgenic mice had any major significant effects on body mass, energy expenditure, even when mice were fed on a high fat diet., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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