IMPORTANCE Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression ...of CKD among individuals with type 2 diabetes. OBJECTIVE To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. MAIN OUTCOMES AND MEASURES Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. RESULTS After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio OR, 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89). CONCLUSIONS AND RELEVANCE A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD among individuals with type 2 diabetes. Sodium intake, within a wide range, and normal protein intake are not associated with CKD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00153101
Here, we describe the construction of pH sensitive surfaces via the synthesis and controlled photografting of pH sensitive, fluorescent tethers from the surface of a reactive polymeric substrate. The ...living radical photografting technique presented makes use of dithiocarbamate-functionalized polymer to graft synthetic poly(ethylene glycol) acrylate succinyl fluorescein. Fluorescence intensity of grafted chains is analyzed as a function of photografting reaction time, graft length, buffer solution pH, and cycling sensors from acidic to basic conditions for optical switching. The graft fluorescence response occurs rapidly in a basic environment and grafted functionalities do not cleave or dramatically deplete (up to 72
h later) upon initial exposure to high or low pH buffers. This behavior is a result of the increased stability when introducing the PEG spacer into the structure of the fluorescein. Ultimately, the pH sensitive grafts developed here demonstrate rapid response times, are easy to produce, and are readily integrated onto a fully polymeric microfluidic device using photolithographic techniques and spatially controlled living radical photografting chemistry. Once integrated, sensors such as these could be useful in monitoring pH changes when mixing, reacting, or introducing new chemicals onto a microdevice like the one presented.
A highly sensitive (pM), efficient (t < 20 min) detection assay was developed by designing surfaces with grafted antibodies. Through this approach, a short half-life antigen, glucagon, was rapidly ...detected in a biologically complex plasma/blood environment. Tailoring of graft composition eliminates the need for time-consuming blocking steps, significantly reducing antigen−antibody incubation times, while maintaining antibody specificity and activity toward target antigen. Grafted antibodies were bound through solvated, mobile polymer chains, thereby circumventing problems associated with antibody accessibility, analyte diffusion, and steric limitations. The efficiency of this assay is provided through grafting synthesized, acrylated antibodies in the presence of PEG monoacrylate. This procedure eliminates the need for blocking steps, due to a decrease in nonspecific protein interactions. These polymerizable antibodies were tethered with a range of densities while retaining biological activity. Moreover, biological activity of acrylated antibodies was compared to that of unmodified antibodies and remained comparable. The acrylated antibodies were grafted from substrate surfaces using controlled radical photopolymerization, maintaining the advantages of classical antibody immobilization techniques while providing improved detection. Through integrating this antibody conjugation chemistry and immunoassay approach with photolithographic techniques, construction of spatial patterns on a microfluidic device was demonstrated for efficient, parallel screening of multiple antigens.
Acrylate monomers were photografted from polymer substrates to create cell responsive chemically and biologically active surfaces that manipulate cell response. Three monomers, polyethylene glycol ...monoacrylate (MW 375
g/mol) (PEG375A), a monomeric extra-cellular matrix protein, and a cell-cleavable fluorescent monomer, were spatially photopatterned from a base substrate. The base substrate consisted of a dithiocarbamate (DTC) functionalized urethane diacrylate/tri(ethylene glycol)diacrylate copolymer and was shown to non-specifically support NIH 3T3 fibroblast cell adhesion. The DTC-containing polymer was further modified by grafting PEG375A to demonstrate selective blocking of cell-material interactions. Next, acrylated collagen type I was patterned onto polymer substrates to further promote specific cell interactions (i.e. by presenting cell-adhesive moieties). Hydrophilic PEG375A grafted patterns were shown to prevent 3T3 fibroblast adhesion to polymer in spatially grafted regions, while biologically active acrylated collagen type I promoted cell-surface interactions. Collagen type I was grafted at varying densities (0–7.5
pmol/grafted square), and the extent of cell adhesion and spreading were evaluated for each of these graft densities using fluorescence microscopy. Finally, methacrylated carboxyfluorescein diacetate (CFDA) was synthesized and photografted onto a cell-adhesive substrate as a cell sensing mechanism. The acetate groups found in the structure of CFDA cleave in the presence of cells. This cell-responsive substrate results in fluorescence indicative of acetate-group cleavage associated with cell interactions that occurs in patterned regions on polymer surfaces. Collectively, the results herein show the utility and application of a spatially and temporally controlled photografting process for designing cell responsive polymer surfaces.
The attachment of antibodies to substrate surfaces is useful for achieving specific detection of antigens and toxins associated with clinical and field diagnostics. Here, acrylated whole antibodies ...were produced through conjugation chemistry, with the goal of covalently photografting these proteins from surfaces in a controlled fashion, to facilitate rapid and sensitive antigenic detection. A living radical photopolymerization chemistry was used to graft the acrylated whole antibodies on polymer surfaces at controlled densities and spatial locations by controlling the exposure time and area, respectively. Copolymer grafts containing these antibodies were synthesized to demonstrate two principles. First, PEG functionalities were introduced to prevent nonspecific protein interactions and improve the reaction kinetics by increasing solvation and mobility of the antibody-containing chains. Both of these properties lead to sensitive (pM) and rapid (<20 min) detection of antigens with this surface modification technique. Second, graft composition was tailored to include multiple antibodies on the same grafted chains, establishing a means for simultaneously detecting multiple antigens on one grafted surface area. Finally, the addition of PEG spacers between the acrylate functionality and the pendant detection antibodies was tuned to enhance the detection of a short-half-life molecule, glucagon, in a complex biological environment, plasma.
Microfluidic devices are commonly fabricated in silicon or glass using micromachining technology or elastomers using soft lithography methods; however, invariable bulk material properties, limited ...surface modification methods and difficulty in fabricating high aspect ratio devices prevent these materials from being utilized in numerous applications and/or lead to high fabrication costs. Contact Liquid Photolithographic Polymerization (CLiPP) was developed as an alternative microfabrication approach that uniquely exploits living radical photopolymerization chemistry to facilitate surface modification of device components, fabrication of high aspect ratio structures from many different materials with numerous covalently-adhered layers and facile construction of three-dimensional devices. This contribution describes CLiPP and demonstrates unique advantages of this new technology for microfabrication of polymeric microdevices. Specifically, the procedure for fabricating devices with CLiPP is presented, the living radical photopolymerization chemistry which enables this technology is described, and examples of devices made using CLiPP are shown.
A linear variable differential transformer (LVDT) was employed to evaluate CO2‐polymer plasticization. Preliminary results on polystyrene‐block‐polybutadiene‐block‐polystyrene (SBS) elastomer are ...presented. At 22 °C under CO2 pressure, SBS undergoes compression due to hydrostatic pressure. However, sample expansion occurs upon depressurization. At 45 °C, SBS undergoes swelling of 0.7% due to CO2 plasticization, while no post‐pressurization expansion is observed. The contrasting result is explained by change in PS domain mobility and discontinuity in the density‐pressure relationship.
Linear displacement of SBS as a function of time at 56 and 134 bar CO2.
To measure the following three relevant outcomes of a personal preparedness curriculum for public health workers: 1) the extent of change (increase) in knowledge about personal preparedness ...activities and knowledge about tools for conducting personal preparedness activities; 2) the extent of change (increase) in preparedness activities performed post-training and/or confidence in conducting these tasks; and 3) an understanding of how to improve levels of personal preparedness using the Extended Parallel Process Model (EPPM) framework.
Cross-sectional preinterventional and postinterventional survey using a convenience sample.
During 2010, three face-to-face workshops were conducted in three locations in West Virginia.
One hundred thirty-one participants (baseline survey); 69 participants (1-year resurvey)-representing West Virginia local health department (LHD) and State Health Department employees.
A 3-hour interactive, public health-specific, face-to-face workshop on personal disaster preparedness.
Change in 1) knowledge about, and tools for, personal preparedness activities; 2) preparedness activities performed post-training and/or confidence in conducting these activities; and 3) the relationship of EPPM categories to personal preparedness activities.
One year postworkshop, 77 percent of respondents reported having personal emergency kits (40 percent at baseline) and 67 percent reported having preparedness plans (38 percent at baseline) suggesting some participants assembled supply kits and plans postworkshop. Within the context of EPPM, respondents in high-threat categories agreed more often than respondents in low-threat categories that severe personal impacts were likely to result from a moderate flood. Compared to respondents categorized as low efficacy, respondents in high-efficacy categories perceived confidence in their knowledge and an impact of their response on their job success at higher rates.
Personal disaster preparedness trainings for the LHD workforce can yield gains in relevant preparedness behaviors and attitudes but may require longitudinal reinforcement. The EPPM can offer a useful threat and efficacy-based lens to understand relevant perceptions surrounding personal disaster preparedness behaviors among LHD employees.
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