Aragon Health Research Institute

Zaragoza, Spain

Aragon Health Research Institute

Zaragoza, Spain
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Chakraborty S.,National Yang Ming University | Nunez D.,CSIC - Institute of Carbochemistry | Nunez D.,Aragon Health Research Institute | Hu S.-Y.,National Yang Ming University | And 9 more authors.
PLoS ONE | Year: 2014

The interaction between leukocyte function-associated antigen-1(LFA-1) and intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in cellular adhesion including the extravasation and inflammatory response of leukocytes, and also in the formation of immunological synapse. However, irregular expressions of LFA-1 or ICAM-1 or both may lead to autoimmune diseases, metastasis cancer, etc. Thus, the LFA-1/ICAM-1 interaction may serve as a potential therapeutic target for the treatment of these diseases. Here, we developed one simple 'in solution' steady state fluorescence resonance energy transfer (FRET) technique to obtain the dissociation constant (Kd) of the interaction between LFA-1 and ICAM-1. Moreover, we developed the assay into a screening platform to identify peptides and small molecules that inhibit the LFA-1/ICAM-1 interaction. For the FRET pair, we used Alexa Fluor 488-LFA-1 conjugate as donor and Alexa Fluor 555-human recombinant ICAM-1 (D1-D2-Fc) as acceptor. From our quantitative FRET analysis, the Kd between LFA-1 and D1-D2-Fc was determined to be 17.93±1.34 nM. Both the Kd determination and screening assay were performed in a 96-well plate platform, providing the opportunity to develop it into a high-throughput assay. This is the first reported work which applies FRET based technique to determine K d as well as classifying inhibitors of the LFA-1/ICAM-1 interaction. © 2014 Chakraborty et al.


Calderon-Larranaga A.,Aragon Health Research Institute | Soljak M.,Imperial College London | Cecil E.,Imperial College London | Valabhji J.,Imperial College London | And 3 more authors.
Diabetic Medicine | Year: 2014

Aim: To determine if hospital admission rates for diabetes complications (acute complications, chronic complications, no complications and hypoglycaemia) were associated with primary care diabetes management. Methods: We performed an observational study in the population in England during the period 2004-2009 (54 741 278 people registered with 8140 general practices). We used multivariable negative binomial regression to model the associations between indirectly standardized hospital admission rates for complications and primary healthcare quality, supply and access indicators, diabetes prevalence and population factors. Results: In multivariate regression models, increasing deprivation (incidence rate ratio: 1.0154; P < 0.001, 95% CI 1.0141-1.0166) and diabetes prevalence (incidence rate ratio: 1.0956; P < 0.001, 95% CI 1.0677-1.1241) were risk factors for admission, while most healthcare covariates, i.e. a larger practice population (incidence rate ratio 0.9999, P = 0.013, 95% CI 0.9999-0.9999), better patient-perceived urgent and non-urgent access to primary care (incidence rate ratio: 0.9989, P = 0.023; 95% CI 0.9979-0.9998 and incidence rate ratio: 0.9988; P = 0.003, 95% CI 0.9980-0.9996, respectively) and better HbA1c target achievement (incidence rate ratio: 0.9971; P < 0.001, 95% CI 0.9958-0.9984), were protective. Diabetes admissions decreased significantly during the period 2004-2009. Conclusions: After controlling for population factors, better scheduled primary care access and glycaemic control were associated with lower hospital admission rates across most complications. There is little rationale to restrict primary care-sensitive condition definitions to acute complications. They should be revised to improve the usefulness of hospital admission data as an outcome measure, and to facilitate international comparisons. The risk of emergency hospital admission should be monitored routinely. © 2014 The Authors.


PubMed | Aragon Health Research Institute
Type: Journal Article | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2014

To determine if hospital admission rates for diabetes complications (acute complications, chronic complications, no complications and hypoglycaemia) were associated with primary care diabetes management.We performed an observational study in the population in England during the period 2004-2009 (54 741 278 people registered with 8140 general practices). We used multivariable negative binomial regression to model the associations between indirectly standardized hospital admission rates for complications and primary healthcare quality, supply and access indicators, diabetes prevalence and population factors.In multivariate regression models, increasing deprivation (incidence rate ratio: 1.0154; P < 0.001, 95% CI 1.0141-1.0166) and diabetes prevalence (incidence rate ratio: 1.0956; P < 0.001, 95% CI 1.0677-1.1241) were risk factors for admission, while most healthcare covariates, i.e. a larger practice population (incidence rate ratio 0.9999, P = 0.013, 95% CI 0.9999-0.9999), better patient-perceived urgent and non-urgent access to primary care (incidence rate ratio: 0.9989, P = 0.023; 95% CI 0.9979-0.9998 and incidence rate ratio: 0.9988; P = 0.003, 95% CI 0.9980-0.9996, respectively) and better HbA1c target achievement (incidence rate ratio: 0.9971; P < 0.001, 95% CI 0.9958-0.9984), were protective. Diabetes admissions decreased significantly during the period 2004-2009.After controlling for population factors, better scheduled primary care access and glycaemic control were associated with lower hospital admission rates across most complications. There is little rationale to restrict primary care-sensitive condition definitions to acute complications. They should be revised to improve the usefulness of hospital admission data as an outcome measure, and to facilitate international comparisons. The risk of emergency hospital admission should be monitored routinely.

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