Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns.

The influence of chronic conditions and the environment on pubertal development. An example from medieval England

Adolescence is a unique period in human development encompassing sexual maturation (puberty) and the physical and psychological transition into adulthood. It is a crucial time for healthy development and any adverse environmental conditions, poor nutrition, or chronic infection can alter the timing of these physical changes; delaying menarche in girls or the age of peak height velocity in boys. This study explores the impact of chronic illness on the tempo of puberty in 607 adolescent skeletons from medieval England (AD 900-1550). A total of 135 (22.2%) adolescents showed some delay in their pubertal development, and this lag increased with age. Of those with a chronic condition, 40.0% (n=24/60) showed delay compared to only 20.3% (n=111/547) of the non-pathology group. This difference was statistically significant. A binary logistic regression model demonstrated a significant association between increasing delay in pubertal stage attainment with age in the pathology group. This is the first time that chronic conditions have been directly associated with a delay in maturation in the osteological record, using a new method to assess stages of puberty in skeletal remains.

A method of evaluating the accuracy of human body thermoregulation models

Human Body Thermoregulation Models have been widely used in the field of human physiology or thermal comfort studies. However there are few studies on the evaluation method for these models. This paper summarises the existing evaluation methods and critically analyses the flaws. Based on that, a method for the evaluating the accuracy of the Human Body Thermoregulation models is proposed. The new evaluation method contributes to the development of Human Body Thermoregulation models and validates their accuracy both statistically and empirically. The accuracy of different models can be compared by the new method. Furthermore, the new method is not only suitable for the evaluation of Human Body Thermoregulation Models, but also can be theoretically applied to the evaluation of the accuracy of the population-based models in other research fields.

Reliability of a method for evaluating porosity in denture base resins

Background: The method of porosity analysis by water absorption has been carried out by the storage of the specimens in pure water, but it does not exclude the potential plasticising effect of the water generating unreal values of porosity. Objective: The present study evaluated the reliability of this method of porosity analysis in polymethylmethacrylate denture base resins by the determination of the most satisfactory solution for storage (S), where the plasticising effect was excluded. Materials and methods: Two specimen shapes (rectangular and maxillary denture base) and two denture base resins, water bath-polymerised (Classico) and microwave-polymerised (Acron MC) were used. Saturated anhydrous calcium chloride solutions (25%, 50%, 75%) and distilled water were used for specimen storage. Sorption isotherms were used to determine S. Porosity factor (PF) and diffusion coefficient (D) were calculated within S and for the groups stored in distilled water. anova and Tukey tests were performed to identify significant differences in PF results and Kruskal-Wallis test and Dunn multiple comparison post hoc test, for D results (alpha = 0.05). Results: For Acron MC denture base shape, FP results were 0.24% (S 50%) and 1.37% (distilled water); for rectangular shape FP was 0.35% (S 75%) and 0.19% (distilled water). For Classico denture base shape, FP results were 0.54% (S 75%) and 1.21% (distilled water); for rectangular shape FP was 0.7% (S 50%) and 1.32% (distilled water). FP results were similar in S and distilled water only for Acron MC rectangular shape (p > 0.05). D results in distilled water were statistically higher than S for all groups. Conclusions: The results of the study suggest that an adequate solution for storing specimens must be used to measure porosity by water absorption, based on excluding the plasticising effect.

Development of molecular assays for the identification of the 11 Eimeria species of the domestic rabbit (Oryctolagus cuniculus)

Coccidiosis are the major parasitic diseases in poultry and other domestic animals including the domestic rabbit (Oryctolagus cuniculus). Eleven distinct Eimeria species have been identified in this host, but no PCR-based method has been developed so far for unequivocal species differentiation. In this work, we describe the development of molecular diagnostic assays that allow for the detection and discrimination of the 11 Eimeria species that infect rabbits. We determined the nucleotide sequences of the ITS1 ribosomal DNAs and designed species-specific primers for each species. We performed specificity tests of the assays using heterologous sets of primers and DNA samples, and no cross-specific bands were observed. We obtained a detection limit varying from 500 fg to 1 pg, which corresponds approximately to 0.8-1.7 sporulated oocysts, respectively. The test reported here showed good reproducibility and presented a consistent sensitivity with three different brands of amplification enzymes. These novel diagnostic assays will permit population surveys to be performed with high sensitivity and specificity, thus contributing to a better understanding of the epidemiology of this important group of coccidian parasites. (C) 2010 Elsevier B.V. All rights reserved.

The Trojan horse method in nuclear astrophysics: recent results

Difficulties in cross-section measurements at very low energies, when charged particles are involved, led to the development of some indirect methods. The Trojan horse method (THM) allows us to bypass the Coulomb effects and has been successfully applied to several reactions of astrophysical interest. A brief review of the THM applications is reported together with some of the most recent results.

Development of impedimetric and optical calcium biosensor by using modified gold electrode with porcine S100A12 protein

We describe the development of a label free method to analyze the interactions between Ca(2+) and the porcine S100A12 protein immobilized on polyvinyl butyral (PVB). The modified gold electrodes were characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and surface plasmon resonance (SPR) techniques. SEM analyses of PVB and PVB-S100A12 showed a heterogeneous distribution of PVB spherules on gold surface. EIS and CV measurements have shown that redox probe reactions on the modified gold electrodes were partially blocked due the adsorption of PVB-S100A12, and confirm the existence of a positive response of the immobilized S100Al2 to the presence of calcium ions. The biosensor exhibited a wide linear response to Ca(2+) concentrations ranging from 12.5 to 200 mM. The PVB-S100A12 seems to be bound to the gold electrode surface by physical adsorption: we observed an increase of 1184.32 m degrees in the SPR angle after the adsorption of the protein on the PVB surface (in an indication that 9.84 ng of S100A12 are adsorbed per mm(2) of the Au-PVB electrode), followed by a further increase of 581.66 m degrees after attachment of the Ca(2+) ions. In addition, no SPR response is obtained for non-specific ions. These studies might be useful as a platform for the design of new reusable and sensitive biosensing devices that could find use in the clinical applications. (C) 2010 Elsevier B.V. All rights reserved.

Development of zirconia-magnesia/zirconia-yttria composite solid electrolytes

Composite solid electrolytes were prepared by thoroughly mixing ZrO2:8 mol% MgO (Z8Mg) and ZrO(2):3 mol% Y(2)O(3) (Z3Y) ceramic powders followed by pressing and sintering at 1500 degrees C/1 h. The properties of the sintered pellets were studied by X-ray diffraction for evaluation of the structural phases by the Rietveld method, by high-temperature dilatometry for analysis of the thermal shrinkage/expansion behavior, and by impedance spectroscopy for determination of the oxide ion conductivity. The x(Z8Mg)+(1-x)(Z3Y) specimens, x= 0.2, 0.4, 0.5, 0.6, 0.8 and 1.0, are partially stabilized (monoclinic, cubic and tetragonal phases) with density >94% of the theoretical density and show thermal shock resistance and electrical conductivity values suitable for high-temperature oxygen gas detection. One-end closed tube samples of the composite solid electrolytes were assembled in Pt/Z8Mg+Z3Y/Cr+Cr(2)O(3)/Pt electrochemical cells for exposure to different levels of oxygen in the 1-850 ppm range. The total electrical conductivity increases for increasing the relative Z3Y content. Addition of Z3Y to Z8Mg (80 wt.%-20 wt.%) suppresses the electronic contribution to the electrical conductivity at 620 degrees C. (c) 2008 Elsevier B.V. All rights reserved.

EVALUATION OF METAL TOXICITY BY A MODIFIED METHOD BASED ON THE FUNGUS GERRONEMA VIRIDILUCENS BIOLUMINESCENCE IN AGAR MEDIUM

Metal cation toxicity to basidiomycete fungi is poorly understood, despite its well-known importance in terrestrial ecosystems. Moreover, there is no reported methodology for the routine evaluation of metal toxicity to basidiomycetes. In the present study, we describe the development of a procedure to assess the acute toxicity of metal cations (Na(+), K(+), Li(+), Ca(2+), Mg(2+), Co(2+), Zn(2+), Ni(2+), Mn(2+), Cd(2+), and Cu(2+)) to the bioluminescent basidiomycete fungus Gerronema viridilucens. The method is based on the decrease in the intensity of bioluminescence resulting from injuries sustained by the fungus mycelium exposed to either essential or nonessential metal toxicants. The assay described herein enables LIS to propose a metal toxicity series to Gerronenia viridilucens based on data obtained from the bioluminescence intensity (median effective concentration [EC50] values) versus metal concentration: Cd(2+) > Cu(2+) > Mn(2+) approximate to Ni(2+) approximate to Co(2+) > Zn(2+) > Mg(2+) > Li(+) > K(+) approximate to Na(+) > Ca(2+), and to shed some li-ht on the mechanism of toxic action of metal cations to basidiomycete fungi. Environ. Toxicol. Chem. 2010;29:320-326. (C) 2009 SETAC

Development of a spectrophotometric Sequential Injection Analysis (SIA) procedure for determination of ammonium: A Response Surface Methodology (RSM) approach

This paper describes the optimization and use of a Sequential Injection Analysis (SIA) procedure for ammonium determination in waters. Response Surface Methodology (RSM) was used as a tool for optimization of a procedure based on the modified Berthelot reaction. The SIA system was designed to (i) prepare the reaction media by injecting an air-segmented zone containing the reagents in a mixing chamber, (ii) to aspirate the mixture back to the holding coil after homogenization, (iii) drive it to a thermostated reaction coil, where the flow is stopped for a previously established time, and (iv) to pump the mixture toward the detector flow cell for the spectrophotometric measurements. Using a 100 mu mol L(-1) ammonium solution, the following factors were considered for optimization: reaction temperature (25 - 45 degrees C), reaction time (30 - 90 s), hypochlorite concentration (20 - 40 mmol L(-1)) nitroprusside concentration (10 - 40 mmol L(-1)) and salicylate concentration (0.1 - 0.3 mol L(-1)). The proposed system fed the statistical program with absorbance data for fast construction of response surface plots. After optimization of the method, figures of merit were evaluated, as well as the ammonium concentration in some water samples. No evidence of statistical difference was observed in the results obtained by the proposed method in comparison to those obtained by a reference method based on the phenol reaction. (C) 2010 Elsevier B.V. All rights reserved.

A New Indirect Electroanalytical Method to Monitor the Contamination of Natural Waters with 4-Nitrophenol Using Multiwall Carbon Nanotubes

The electrochemical detection of the hazardous pollutant 4-nitrophenol (4-NP) at low potentials, in order to avoid matrix interferences, is an important research challenge. This study describes the development, electrochemical characterization and utilization of a multiwall carbon nanotube (MWCNT) film electrode for the quantitative determination of 4-NP in natural water. Electrochemical impedence spectroscopy measurements showed that the modified surface exhibits a decrease of ca. 13 times in the charge transfer resistance when compared with a bare glassy carbon (GC) surface. Voltammetric experiments showed the possibility to oxidize a hydroxylamine layer (produced by the electrochemical reduction of 4-NP on the GC/MWNCT surface) in a potential region which is approximately 700 mV less positive than that needed to oxidize 4-NP, thus minimizing the interference of matrix components. The limit of detection for 4-NP obtained using square-wave voltammetry (0.12 mu mol L(-1)) was lower than the value advised by EPA. A natural water sample from a dam located in Sao Carlos (Brazil) was spiked with 4-NP and analyzed by the standard addition method using thee GC/MWCNT electrode, without any further purification step. the recovery procedure yielded a value of 96.5% for such sample, thus confirming the suitability of the developed method to determine 4-NP in natural water samples. The electrochemical determination was compared with that obtained by HPLC with UV-vis detection.

Anticorrosive cerium-based coatings prepared by the sol-gel method

The development of efficient anti-corrosion and environmentally friendly coating systems are needed for the replacement of the highly toxic Cr-based conversion coatings for corrosion protection of aluminum alloys. In this study, we demonstrate that the direct application of ceramic cerium-based sol-gel coatings to AA7075-T6 substrates produces high-performance anti-corrosion layers. Electrochemical experiments and analyses of the microstructure demonstrate that the protective layers are very efficient for the passivation of the alloy surfaces operating as both passive and active barrier for corrosion protection.

Development of an Analytical Methodology for Quantification of Strong Acid in Diesel Oil

Many factors can affect the quality of diesel oil, in particular the degradation processes that are directly related to some organosulfur compounds. During the degradation process, these compounds are oxidized into their corresponding sulfonic acids, generating a strong acid content during the process. p-Toluene sulfonic acid analysis was performed using the linear sweep voltammetry technique with a platinum ultramicroelectrode in aqueous solution containing 3 mol L(-1) potassium chloride. An extraction step was introduced prior to the voltammetric detection in order to avoid the adsorption of organic molecules, which inhibit the electrochemical response. The extraction step promoted the transference of sulfonic acid from the diesel oil to an aqueous phase. The method was accurate and reproducible, with detection and quantification limits of 5 ppm and 15 ppm, respectively. Recovery of sulfonic acid was around 90%.

Development of a new stir bar sorptive extraction coating and its application for the determination of six pesticides in sugarcane juice

In this article, a novel polydimethylsiloxane/activated carbon (PDMS-ACB) material is proposed as a new polymeric phase for stir bar sorptive extraction (SBSE). The PDMS-ACB stir bar, assembled using a simple Teflon (R)/glass capillary mold, demonstrated remarkable stability and resistance to organic solvents for more than 150 extractions. The SBSE bar has a diameter of 2.36 mm and a length of 2.2 cm and is prepared to contain 92 mu L of polymer coating. This new PDMS-ACB bar was evaluated for its ability to determine the quantity of pesticides in sugarcane juice samples by performing liquid desorption (LD) in 200 mu L of ethyl acetate and analyzing the solvent through gas chromatography coupled with mass spectrometry (GC-MS). A fractional factorial design was used to evaluate the main parameters involved in the extraction procedure. Then, a central composite design with a star configuration was used to optimize the significant extraction parameters. The method used demonstrated a limit of quantification (LOQ) of 0.5-40 mu g/L, depending on the analyte detected; the amount of recovery varied from 0.18 to 49.50%, and the intraday precision ranged from 0.072 to 8.40%. The method was used in the analysis of real sugarcane juice samples commercially available in local markets.

Development and Application of a Highly Selective Biomimetic Sensor for Detection of Captopril, an Important Ally in Hypertension Control

A biomimetic sensor is proposed as a promising new analytical method for determination of captopril in different classes of samples. The sensor was prepared by modifying a carbon paste electrode with iron (II) phthalocyanine bis(pyridine) [FePe(dipy)] complex. Amperometric measurements in a batch analytical mode were first carried out in order to optimize the sensor response. An applied potential lower than 0.2 V vs Ag vertical bar AgCl in 0.1 mol L(-1) of TRIS buffer at pH 8.0 provided the best response, with a linear range of 2.5 x 10(-5) to 1.7 x 10(-4) mol L(-1). A detailed investigation of the selectivity of the sensor, employing seventeen other drugs, was also performed. Recovery studies were carried out using biological and environment samples in order to evaluate the sensor`s potential for use with these sample classes. Finally, the performance of the biomimetic sensor was optimized in a flow injection (FIA) system using a wall jet electrochemical cell. Under optimized flow conditions, a broad linear response range, from 5.0 x 10(-4) to 2.5 x 10(-2) mol L(-1), was obtained for captopril, with a sensitivity of 210 +/- 1 mu A L mol(-1).