Electronic health records: new opportunities for clinical research.

Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups.

Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans.

Background: The digestive hydrolysis of dietary proteins leads to the release of peptides in the intestinal tract, where they may exert a variety of functions, but their characterization and quantification are difficult.

Objectives: We aimed to characterize and determine kinetics of the formation of peptides present in the jejunum of humans who ingested casein or whey proteins by using mass spectrometry and to look for and quantify bioactive peptides.

Design: Subjects were equipped with a double-lumen nasogastric tube that migrated to the proximal jejunum.

Detection of avian retroviruses in vaccines by amplification on DF-1 cells with immunostaining and fluorescent product-enhanced reverse transcriptase endpoint methods.

In order to ensure the safety of vaccines produced on avian cells, rigorous testing for the absence of avian retroviruses must be performed. Current methods used to detect avian retroviruses often exhibit a high invalid-test/false-positive rate, rely on hard-to-secure reagents, and/or have readouts that are difficult to standardize. Herein, we describe the development and validation of two consistent and sensitive methods for the detection of avian retroviruses in vaccines: viral amplification on DF-1 cells followed by immunostaining for the detection of avian leukosis virus (ALV) and viral amplification on DF-1 cells followed by fluorescent product-enhanced reverse transcriptase (F-PERT) for the detection of all avian retroviruses.

Cost-effectiveness simulation model of biologic strategies for treating to target rheumatoid arthritis in Germany.

Objectives: The treatment of active rheumatoid arthritis (RA) usually requires different therapeutic options used sequentially in case of an insufficient response (IR) to previous agents. Since there is a lack of clinical trials comparing biologic treatment sequences, simulation models might add to the understanding of optimal treatment sequences and their cost-effectiveness. The objective of this study was to assess the cost-effectiveness of different biologic treatment strategies in patients with an IR to anti-TNF agents, based on levels of disease activity from the German public payer's perspective.

Spatial and temporal MRI profile of ischemic tissue after the acute stages of a permanent mouse model of stroke.

Object: To characterize the progression of injured tissue resulting from a permanent focal cerebral ischemia after the acute phase, Magnetic Resonance Imaging (MRI) monitoring was performed on adult male C57BL/6J mice in the subacute stages, and correlated to histological analyses.

Material And Methods: Lesions were induced by electrocoagulation of the middle cerebral artery. Serial MRI measurements and weighted-images (T2, T1, T2* and Diffusion Tensor Imaging) were performed on a 9.

The heat treatment and the gelation are strong determinants of the kinetics of milk proteins digestion and of the peripheral availability of amino acids.

This study aimed to determine the kinetics of milk protein digestion and amino acid absorption after ingestion of four dairy matrices by six minipigs: unheated or heated skim milk and corresponding rennet gels. Digestive contents and plasma samples were collected over a 7 h-period after meal ingestion. Gelation of milk slowed down the outflow of the meal from the stomach and the subsequent absorption of amino acids, and decreased their bioavailability in peripheral blood.

Interest of modelling in rheumatoid arthritis.

Such as prospective studies can provide evidence-based information for clinicians and regulatory agencies, modelling studies provide useful information when experimental studies are to complex, too long, or too expensive to carry out. If modelling has been widely used in pharmacokinetics, it is in the field of pharmacoeconomics that numerous models have been published in recent years, including models relevant to the management of rheumatoid arthritis (RA). The most common modelling techniques published in RA are decision trees and Markov models which are used to perform cost-effectiveness and cost-utility analyses using real or simulated populations.

Targeting tumor cell invasion and dissemination in vivo by an aptamer that inhibits urokinase-type plasminogen activator through a novel multifunctional mechanism.

Data accumulated over the latest two decades have established that the serine protease urokinase-type plasminogen activator (uPA) is a potential therapeutic target in cancer. When designing inhibitors of the proteolytic activity of serine proteases, obtaining sufficient specificity is problematic, because the topology of the proteases' active sites are highly similar. In an effort to generate highly specific uPA inhibitors with new inhibitory modalities, we isolated uPA-binding RNA aptamers by screening a library of 35 nucleotides long 2'-fluoro-pyrimidine RNA molecules using a version of human pro-uPA lacking the epidermal growth factor-like and kringle domains as bait.

Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia.

Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known.

A Bayesian network approach to the study of historical epidemiological databases: modelling meningitis outbreaks in the Niger.

Objective: To develop a tool for evaluating the risk that an outbreak of meningitis will occur in a particular district of the Niger after outbreaks have been reported in other, specified districts of the country.

Methods: A Bayesian network was represented by a graph composed of 38 nodes (one for each district in the Niger) connected by arrows. In the graph, each node directly influenced each of the "child" nodes that lay at the ends of the arrows arising from that node, according to conditional probabilities.

In vivo digestion of infant formula in piglets: protein digestion kinetics and release of bioactive peptides.

The first months of life correspond to a key period in human life where dramatic physiological changes (establishment of microbiota, development of the immune system, etc.) occur. In order to better control these changes it is necessary to understand the behaviour of food in the gastrointestinal tract of the newborn.

Defensive spending on tap water substitutes: the value of reducing perceived health risks.

We examine factors that explain consumer spending on tap water substitutes using information from a national survey undertaken with a representative set of Canadian respondents. We develop a model to predict the percentage of households that undertake such spending for the purpose of reducing perceived health risks from tap water consumption. Using results from the model we estimate the magnitude of defensive expenditures to be over half a billion dollars (2010 US$) per year for Canada, as a whole.

Confirmation and follow-up of neurocysticercosis by real-time PCR in cerebrospinal fluid samples of patients living in France.

Neurocysticercosis diagnosis is based on a combination of clinical, epidemiological, radiological, and immunological findings. We describe a real-time PCR assay for the confirmation of neurocysticercosis diagnosis in cerebrospinal fluid. The assay, tested on samples from nine patients living in France and diagnosed with neurocysticercosis, had a detection rate of 83.

Nucleic acid aptamers against proteases.

Proteases are potential or realized therapeutic targets in a wide variety of pathological conditions. Moreover, proteases are classical subjects for studies of enzymatic and regulatory mechanisms. We here review the literature on nucleic acid aptamers selected with proteases as targets.

Tumor-targeted polydiacetylene micelles for in vivo imaging and drug delivery.

In vivo tumor targeting and drug delivery properties of small polymerized polydiacetylene (PDA) micelles (∼10 nm) is investigated in a murine MDA-MB-231 xenograft model of breast cancer. Three micelles with different surface coatings are synthesized and tested for their ability to passively target tumor through the enhanced permeability and retention effect. After injection (24 h), fluorescence diffuse optical tomographic imaging indicates a tumor uptake of nearly 3% of the injected dose for the micelles with a 2 kDa poly(ethylene glycol) (PEG)-coating (PDA-PEG2000).

Assessing the cost-effectiveness of biologic agents for the management of moderate-to-severe rheumatoid arthritis in anti-TNF inadequate responders in Italy: a modelling approach.

Objectives: The objective of this study is to assess cost-effectiveness of different biologic strategies in patients with moderate-to-severe active RA after an insufficient response to anti-TNF agents within the context of the Italian healthcare system.

Methods: Simulation models were developed allowing for potential biologic therapy switch at each 6-month time point in case of an insufficient response to the previous biologic agent. Biologic treatments included etanercept, abatacept, adalimumab, rituximab or infliximab.

Modelling cost-effectiveness of biologic treatments based on disease activity scores for the management of rheumatoid arthritis in Spain.

Background. The objective of this simulation model was to assess the cost-effectiveness of different biological treatment strategies based on levels of disease activity in Spain, in patients with moderate to severe active RA and an insufficient response to at least one anti-TNF agent. Methods.

Nisin quantification by ELISA allows the modeling of its apparent diffusion coefficient in model cheeses.

The diffusion of small solutes in cheese is of key importance for most enzymatic reactions involved in the ripening process. However, only a limited amount of data is available on salt diffusion and practically none on peptide diffusion. Nisin, a bacteriocin peptide, migrated in model cheeses made from ultrafiltered (UF) retentate.

Topography of the casein micelle surface by surface plasmon resonance (SPR) using a selection of specific monoclonal antibodies.

Several theoretical models of the casein micelle structure have been proposed in the past, but the exact organization of the four individual caseins (α(s1), α(s2), β, and κ) within this supramolecular structure remains unknown. The present study aims at determining the topography of the casein micelle surface by following the interaction between 44 monoclonal antibodies specific for different epitopes of α(s1)-, α(s2)-, β-, and κ-casein and the casein micelle in real time and no labeling using a surface plasmon resonance (SPR)-based biosensor. Although the four individual caseins were found to be accessible for antibody binding, data confirmed that the C-terminal extremity of κ-casein was highly accessible and located at the periphery of the structure.

Evaluation of thermal and moisture management properties on knitted fabrics and comparison with a physiological model in warm conditions.

This study reports on an experimental investigation of physical properties on the textile thermal comfort. Textile properties, such as thickness, relative porosity, air permeability, moisture regain, thermal conductivity, drying time and water-vapour transmission rate have been considered and correlated to the thermal and vapour resistance, permeability index, thermal effusivity and moisture management capability in order to determine the overall comfort performance of underwear fabrics. The results suggested that the fibre type, together with moisture regain and knitted structure characteristics appeared to affect some comfort-related properties of the fabrics.

Dietary antigens, epitope recognition, and immune complex formation in recent onset psychosis and long-term schizophrenia.

Peptides derived from dietary antigens such as bovine milk caseins are opioid receptor ligands and contribute to schizophrenia-associated hyperpeptidemia and hyperpeptiduria. The IgG antibody response to bovine caseins is increased in schizophrenia and recent onset psychosis. To identify specific casein peptide sequences that are antigenic in patients vs controls, we measured serum IgG binding to 10-26 amino acid long linear epitopes of casein with immunoassays for the entire group (n=95 recent onset psychosis; n=103 long-term schizophrenia; n=65 control), and with peptide microarray libraries in a casein-sensitive subset (n=14 recent onset; n=10 control).

Immune activation by casein dietary antigens in bipolar disorder.

Objectives:   Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals.

Direct cost-modeling of rheumatoid arthritis according to disease activity categories in France.

Objective: The objective of this cost-of-illness study was to assess the use of direct medical resources, excluding drug costs, by patients with rheumatoid arthritis (RA) in France, and to construct cost estimates according to level of disease activity.

Methods: Three categories of RA disease activity were defined according to Disease Activity Score 28-joint count (DAS28) thresholds: remission (DAS28 < 2.6), low disease activity state (LDAS; i.

Serum-stable RNA aptamers to urokinase-type plasminogen activator blocking receptor binding.

The serine proteinase urokinase-type plasminogen activator (uPA) is widely recognized as a potential target for anticancer therapy. Its association with cell surfaces through the uPA receptor (uPAR) is central to its function and plays an important role in cancer invasion and metastasis. In the current study, we used systematic evolution of ligands by exponential enrichment (SELEX) to select serum-stable 2'-fluoro-pyrimidine-modified RNA aptamers specifically targeting human uPA and blocking the interaction to its receptor at low nanomolar concentrations.