Exploration of the global antioxidant capacity of the stratum corneum by cyclic voltammetry

Cyclic voltammetry is proposed as a new method for evaluating the antioxidant capacity of skin based on the reducing properties of low molecular weight antioxidants (LMWA). Experiments were performed simply by recording the anodic current at 0.9 V/SCE of a platinum microelectrode placed directly on the epidermis surface without any gel or water. This method ensured a direct, rapid (less than 1 min), reliable (accuracy 12%) and non-invasive measurement of the global antioxidant capacity of the stratum corneum with a high spatiotemporal resolution. At the same time, the pH of the skin surface was determined by recording the cathodic current at 0 V/SCE. Based on an exploratory study involving nine volunteer subjects, the evolution of the amperometric response of the microelectrode with time revealed a periodic modification of the redox properties

Functional health literacy in Spanish-speaking Latinas seeking breast cancer screening through the National Breast and Cervical Cancer Screening Program

Samantha Garbers1, Karen Schmitt2, Anne Marie Rappa2, Mary Ann Chiasson11Public Health Solutions, New York, NY, USA; 2Columbia University Breast Cancer Screening Program, New York, NY, USABackground: This analysis examines the association between functional health literacy and follow-up after mammography among women receiving breast cancer screening at a National Breast and Cervical Cancer Early Detection Program site in New York City that provides universal bilingual case management.Methods: A total of 707 Latinas who spoke Spanish as their primary language completed a survey of health and demographic characteristics and the Test of Functional Health Literacy in Spanish (TOFHLA-S). Survey results were matched with clinical outcome data.Results: Among the survey participants, 98% were foreign-born and 99% had no health insurance. While the study found significant differences in access to health information and past screening behavior, women without adequate health literacy in Spanish were no less likely to receive clinical resolution of abnormal mammograms within 60 days (81.8% overall; n = 110) or to return for a repeat mammogram within 18 months (57.2% overall; n = 697). In fact, among those referred for a Pap test (n = 310), women without adequate health literacy were more likely to receive a Pap test within 60 days of their mammogram than those with adequate health literacy (82% compared to 71%, OR: 1.83, 95% CI: 1.04–3.22).Discussion: The lack of significantly lower follow-up outcomes among women with inadequate and marginal functional health literacy in this population of primary Spanish-speaking Latinas suggests that, once women have accessed screening services, programmatic approaches may exist to mitigate barriers to follow-up and to ensure optimal cancer screening outcomes for women of all literacy levels.Keywords: health literacy, mammography, Latinas, case management, cancer screenin

Knockdown of Myosin Va Isoforms by RNAi as a Tool to Block Melanosome Transport in Primary Human Melanocytes

The movement of melanosomes, dense melanin-containing organelles, within human melanocytes is actin-dependent and mediated through the formation of a Rab27a-Slac2-a–myosin Va (MyoVa) protein complex. We previously showed that only the melanocyte-specific exon F isoforms of MyoVa are involved in melanosome transport to the dendrite extremities. Here, we investigate siRNA to downregulate the exon F-containing isoforms of MyoVa in primary human melanocytes. Efficient and specific knockdown of the MyoVa exon F isofoms were shown at both mRNA and protein levels. Further, a stable shRNA against the MyoVa exon F isoforms was prepared by using a lentiviral system to improve and confirm the silencing effect in hard-to-transfect melanocyte cells. Immunofluorescence microscopy shows that knockdown of the exon F isoforms results in blockade of intramelanocytic melanosome transport due to the inability to form the Rab27a-Slac2-a–MyoVa tripartite complex. Interestingly, the observed phenotypic effect (that is, perinuclear accumulation of melanosomes) is the same as that seen in melanocytes from patients with human Griscelli syndrome causing abnormal pigmentation. We conclude that our siRNA-based strategy provides a previously unreported tool to block the intracellular melanosome movement in primary human melanocytes and may become an innovative drug to treat hyperpigmentation

Thermal and vibrational characterization of human skin

For a better understanding of the molecular and organizational changes in human dermis, biophysical methods were tested. The aim of this study was to find suitable and reproducible biomarkers for further clinical studies on intrinsic and extrinsic aging of dermis. Thermoporometry, hydric organization and thermal transitions of fresh and frozen skins were determined by differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) was used to identify the absorption bands of the dermis especially in the 1800–1000 cm−1 zone and to discriminate between the different secondary structures of proteins. A widening of the pore size distribution is evidenced with freezing, but there is no significant difference between the hydric organization and the endothermic collagen denaturation of fresh and frozen skins. The global FTIR spectra and the second derivative spectra in the scanned zone are also identical in fresh and frozen dermis, validating the storage protocol. DSC and FTIR are well-suited techniques to characterize human skin, giving accurate results with high reproducibility. The acquisition of thermal and vibrational biomarkers of the skin at the mesoscale and nanoscale contributes to its better knowledge and is promising for further studies on skin aging

Chain dynamics of human dermis by Thermostimulated currents: a tool for new markers of aging

Abstract Background/purpose: The purpose of this clinical study was to identify dielectric markers to complete a previous thermal and vibrational study on the molecular and organizational changes in human dermis during intrinsic and extrinsic aging. Methods: Sun-exposed and non-exposed skin biopsies were collected from 28 women devised in two groups (20-30 and ≥60 years old). The dielectric relaxation modes associated with localized and delocalized dynamics in the fresh and dehydrated state were determined by the Thermostimulated currents technique (TSC). Results: Intrinsic and extrinsic aging induced significant evolution of some of the dielectric parameters of localized and delocalized dynamics of human skin. With photo-aging, freezable water forms a segregated phase in dermis and its dynamics is close to free water, what evidences the major role of extrinsic aging on water organization in human skin. Moreover, TSC indicators highlight the restriction of localized mobility with intrinsic aging due to glycation, and the cumulative effect of chronological aging and photo-exposition on the molecular mobility of the main structural proteins of the dermis at the mesoscopic scale. Conclusion: TSC is a well-suited technique to scan the molecular mobility of human skin. It can be uses as a relevant complement of vibrational and thermal characterization to follow human skin modifications with intrinsic and extrinsic aging

Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia

<p>Abstract</p> <p>Background</p> <p>The t(12;21)(p13;q22) translocation is found in 20 to 25% of cases of childhood B-lineage acute lymphoblastic leukemia (B-ALL). This rearrangement results in the fusion of <it>ETV6 </it>(<it>TEL</it>) and <it>RUNX1 </it>(<it>AML1</it>) genes and defines a relatively uniform category, although only some patients suffer very late relapse. <it>TEL/AML1</it>-positive patients are thus an interesting subgroup to study, and such studies should elucidate the biological processes underlying TEL/AML1 pathogenesis. We report an analysis of gene expression in 60 children with B-lineage ALL using Agilent whole genome oligo-chips (44K-G4112A) and/or real time RT-PCR.</p> <p>Results</p> <p>We compared the leukemia cell gene expression profiles of 16 <it>TEL/AML1</it>-positive ALL patients to those of 44 <it>TEL/AML1</it>-negative patients, whose blast cells did not contain any additional recurrent translocation. Microarray analyses of 26 samples allowed the identification of genes differentially expressed between the TEL/AML1-positive and negative ALL groups. Gene enrichment analysis defined five enriched GO categories: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding, associated with 14 genes -<it>RUNX1, TCFL5, TNFRSF7, CBFA2T3</it>, <it>CD9</it>, <it>SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7</it>, <it>SEMA6A, CTGF, LSP1, TFPI </it>– highlighting the biology of the <it>TEL/AML1 </it>sub-group. These results were first confirmed by the analysis of an additional microarray data-set (7 patient samples) and second by real-time RT-PCR quantification and clustering using an independent set (27 patient samples). Over-expression of <it>RUNX1 (AML1) </it>was further investigated and in one third of the patients correlated with cytogenetic findings.</p> <p>Conclusion</p> <p>Gene expression analyses of leukemia cells from 60 children with <it>TEL/AML1</it>-positive and -negative B-lineage ALL led to the identification of five biological processes, associated with 14 validated genes characterizing and highlighting the biology of the <it>TEL/AML1</it>-positive ALL sub-group.</p

Raman characterization of human skin aging

Skin aging is a complex biological process mixing intrinsic and extrinsic factors, such as sun exposure. At the molecular level, skin aging affects in particular the extracellular matrix proteins. Materials and Methods: Using Raman imaging, which is a nondestructive approach appropriate for studying biological samples, we analyzed how aging modifies the matrix proteins of the papillary and reticular dermis. Biopsies from the buttock and dorsal forearm of volunteers younger than 30 and older than 60 were analyzed in order to identify chronological and photoaging processes. Analyses were performed on skin section, and Raman spectra were acquired separately on the different dermal layers. Results: We observed differences in dermal matrix structure and hydration state with skin aging. Chronological aging alters in particular the collagen of the papillary dermis, while photoaging causes a decrease in collagen stability by altering proline and hydroxyproline residues in the reticular dermis. Moreover, chronological aging alters glycosaminoglycan content in both dermal compartments. Conclusion: Alterations of the papillary and reticular dermal matrix structures during photo-and chronological aging were clearly depicted by Raman spectroscopy