Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

p53 gene therapy in vivo of herpatocellular and liver metastatic colorectal cancer

Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers. Colorectal cancer is leading cause of cancer mortality in the United States, whereas hepatocellular cancer is the leading worldwide cause of cancer death; the liver is a primary site of morbidity in both diseases. Because systemic tumor suppressor gene therapy is currently not feasible, we have chosen to develop a regional form of such therapy directed at primary or metastatic liver neoplasms. Gene replacement therapy with p53 is a promising new strategy to treat advanced human cancers.     

PROBLEM-SOLVING SUPPORT FOR TQM A Hypertext Approach

New IS technology is contributing to continuous quality improvement throughout the organization. Hypertext and hypermedia offer new ways for decision makers to gain easy and relevant access to information. By combining hypertext with total quality tools, decision makers are able to explore the richness of data bases in more creative and useful ways. This article describes how you can develop a hypertext system that can help employees improve their job performance through better problem solving.     

Methodological issues in outcome studies of school-based interventions for the prevention of adolescent depression.

Several methodological and ethical issues are addressed in the context of 3 related school-based studies of the primary and targeted prevention of depressive symptoms and disorder in high school adolescents. These issues include obtaining S consent and the protection of confidentiality, minimizing attrition over long-term follow-up periods, the "unit of assignment" issue common to most school-based research, and ensuring therapist fidelity to the intervention protocol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medical savings accounts: opportunities for cost savings?

Interest in medical savings accounts (MSAs) as a potential tool to reduce healthcare costs has been widespread. A small number of countries have either implemented or run pilot programs of MSAs, and vigorous policy debates have taken place in several other countries about the potential merits of introducing MSAs as a method of paying for health care. In this paper we develop a model to assess the cost saving potential of MSAs in a publicly funded healthcare system. We assume that the public healthcare payer may choose between reimbursing healthcare expenditures through an MSA or through a form of third‐party payer insurance. We use the model to identify the conditions under which MSAs may reduce costs. We illustrate using data on healthcare expenditures from Canada.     

Nanostructured polymer blends: Synthesis and structure

Nanostructured polymer blends prepared via anionic ring opening polymerizations of cyclic monomers in the presence of a pre-made polymer melt exhibit a number of special properties over traditional polymer blends and homopolymers. Here, we report on a simple and versatile method of in situ polymerization of macrocyclic carbonates in the presence of a maleic anhydride polypropylene (mPP) matrix and a surface-active compatibilizer (i.e. PC grafted onto a mPP backbone generated in situ) to yield a micro- and nanostructured polymer blends consisting of a polycarbonate (PC) minor phase, and a polypropylene (PP) major phase. By varying the processing conditions and concentration of the macrocyclic carbonate it was possible to reduce the size of the PC dispersions to an average minor diameter of 150 nm. NMR and TEM characterizations indicate that the PC dispersions do not influence crystal content in the PP phase. Overall, the results point to a simple strategy and versatile route to new polymeric materials with enhanced benefits.     

Androgen-dependent protein interactions within an intron 1 regulatory region of the 20-kDa protein gene

The 20-kDa protein gene is androgen regulated in rat ventral prostate. Intron 1 contains a 130-base pair complex response element (D2) that binds androgen (AR) and glucocorticoid receptor (GR) but transactivates only with AR in transient cotransfection assays in CV1 cells using the reporter vector D2-tkCAT. To better understand the function of this androgen-responsive unit, nuclear protein interactions with D2 were analyzed by DNase I footprinting in ventral prostate nuclei of intact or castrated rats and in vitro with ventral prostate nuclear protein extracts from intact, castrated, and testosterone-treated castrated rats. Multiple androgen-dependent protected regions and hypersensitive sites were identified in the D2 region with both methods. Mobility shift assays with 32P-labeled oligonucleotides spanning D2 revealed specific interactions with ventral prostate nuclear proteins. Four of the D2-protein complexes decreased in intensity within 24 h of castration. UV cross-linking of the androgen-dependent DNA binding proteins identified protein complexes of approximately 140 and 55 kDa. The results demonstrate androgen-dependent nuclear protein-DNA interactions within the complex androgen response element D2.