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.     

Reduced texaphyrin: A ratiometric optical sensor for heavy metals in aqueous solution

We report here a water-soluble metal cation sensor system based on the as-prepared or reduced form of an expanded porphyrin, texaphyrin. Upon metal complexation, a change in the redox state of the ligand occurs that is accompanied by a color change from red to green. Although long employed for synthesis in organic media, we have now found that this complexation-driven redox behavior may be used to achieve the naked eye detectable colorimetric sensing of several number of less-common metal ions in aqueous media. Exposure to In(III), Hg(II), Cd(II), Mn(II), Bi(III), Co(II), and Pb(II) cations leads to a colorimetric response within 10 min. This process is selective for Hg(II) under conditions of competitive analysis. Furthermore, among the subset of response-producing cations, In(III) proved unique in giving rise to a ratiometric change in the ligand-based fluorescence features, including an overall increase in intensity. The cation selectivity observed in aqueous media stands in contrast to what is seen in organic solvents, where a wide range of texaphyrin metal complexes may be prepared. The formation of metal cation complexes under the present aqueous conditions was confirmed by reversed phase high-performance liquid chromatography, ultra-violet-visible absorption and fluorescence spectroscopies, and high-resolution mass spectrometry.     

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.     

The ultrasound appearances of neonatal renal vein thrombosis

Renal vein thrombosis (RVT) is the most frequently occurring vascular condition in the new-born kidney. The predisposing factors include dehydration, sepsis, birth asphyxia, maternal diabetes, polycythaemia and the presence of an indwelling umbilical venous catheter. (RVT) may present clinically with a flank mass, haematuria, hypertension or renal failure. Many imaging modalities have been employed, but ultrasound is the technique most commonly used in the evaluation of neonates with suspected RVT. Thrombosis commences in the small renal veins and subsequently propagates via larger interlobar veins to the main renal vein and inferior vena cava (IVC). The ultrasound appearances depend upon the stage at which the examination is performed and extent of the thrombus. Initially, the interlobular and interlobar thrombus appears as highly echogenic streaks. These streaks commence in a peripheral, focal segment of the involved kidney and only persist for a few days. In the first week the affected kidney swells and becomes echogenic with prominent echopoor medullary pyramids. Later, the swelling increases and the kidney becomes heterogenous with loss of corticomedullary differentiation. Grey scale ultrasound readily demonstrates thrombus within the renal vein and IVC. Adrenal haemorrhage is a recognized association and may be identified ultrasonically. Colour Doppler scanning provides additional information. In the early stages of RVT, colour Doppler may demonstrate absent intrarenal and renal venous flow. Ultimately, the kidney may recover, show focal scarring or become atrophic. Thus, ultrasound provides an accessible and reliable tool in the assessment of suspected neonatal RVT.     

Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid

Tumor necrosis factor alpha (TNF-alpha) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-alpha gene promoter polymorphisms and TNF-alpha levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The -308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (chi2 for trend, P = 0.032; allele frequency, 0.163 in patients and 0.099 in controls; chi2, P = 0.025). For the -238A allele, the association was similar but not significant. The disease association was highly significant when the number of either -308A or -238A sites in an individual was considered (P = 0.003). TNF-alpha promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-alpha was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-alpha (P = 0.015). Among patients, detectable TNF-alpha in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-alpha plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.     

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.