Food Insecurity Increases HIV Risk Among Young Sex Workers in Metro Vancouver, Canada.

This research aimed to determine the effect of food insecurity on sexual HIV risk with clients among youth sex workers (YSWs) <30 years in Metro Vancouver, Canada. Data were drawn from a prospective community cohort of sex workers (2010-2013). We examined the independent relationship between YSWs' food insecurity and being pressured into sex without a condom by clients ("client condom refusal"). Of 220 YSWs, 34.5 % (n = 76) reported client condom refusal over the 3.5-year study period and 76.4 % (n = 168) reported any food insecurity. Adjusting for other HIV risk pathways, food insecurity retained an independent effect on client condom refusal (AOR 2.08, 95 % CI 1.23-3.51), suggesting that food insecurity is significantly associated with HIV risk among YSWs. This study indicates a critical relationship between food insecurity and HIV risk, and demonstrates YSWs' particular vulnerability. Public policies for food assistance as a harm reduction measure may be key to addressing this disparity.

A 3D-psoriatic skin model for dermatological testing: The impact of culture conditions.

BACKGROUND: Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of compound effects. Consequently, pharmaceutical investigators are searching for preclinical models that closely resemble original tissue for predicting clinical outcomes. METHODS: The current research aims to compare the impact of using serum-free medium instead of complete culture medium during the last step of psoriatic skin substitute reconstruction. Skin substitutes were produced according to the self-assembly approach. RESULTS: Serum-free conditions have no negative impact on the reconstruction of healthy or psoriatic skin substitutes presented in this study regarding their macroscopic or histological appearances. ATR-FTIR results showed no significant differences in the CH2 bands between psoriatic substitutes cultured with or without serum, thus suggesting that serum deprivation did not have a negative impact on the lipid organization of their stratum corneum. Serum deprivation could even lead to a better organization of healthy skin substitute lipids. Percutaneous analyses demonstrated that psoriatic substitutes cultured in serum-free conditions showed a higher permeability to hydrocortisone compared to controls, while no significant differences in benzoic acid and caffeine penetration profiles were observed. CONCLUSIONS: Results obtained with this 3D-psoriatic skin substitute demonstrate the potential and versatility of the model. It could offer good prediction of drug related toxicities at preclinical stages performed in order to avoid unexpected and costly findings in the clinic. GENERAL SIGNIFICANCE: Together, these findings offer a new approach for one of the most important challenges of the 21st century, namely, prediction of drug toxicity.

Characterization of a psoriatic skin model produced with involved or uninvolved cells.

Current knowledge suggests that uninvolved psoriatic skin could demonstrate characteristics associated with both normal and involved psoriatic skins. However, the triggering factor allowing the conversion of uninvolved skin into a psoriatic plaque is not fully understood. To counter this lack of information, we decided to develop pathological skin substitutes produced with uninvolved psoriatic cells, in order to better characterize the uninvolved psoriatic skin. Substitutes were produced using the self-assembly approach. Macroscopic, immunohistochemical, permeability and physicochemical results showed that involved substitutes had a thicker epidermis, higher cell proliferation, abnormal cell differentiation and a more permeable and disorganized stratum corneum compared with normal substitutes. Various results were observed using uninvolved cells, leading to two proposed profiles: profile 1 was suggested for uninvolved skin substitutes mimicking the results obtained with normal skin substitutes; and profile 2 was dedicated to those mimicking involved skin substitutes in all aspects that were analysed. In summary, uninvolved substitutes of profile 1 had a thin, well-organized epidermis with normal cell proliferation and differentiation, such as observed with normal substitutes, while uninvolved substitutes of profile 2 showed an inverse trend, i.e. a thicker epidermis, higher cell proliferation, abnormal cell differentiation and a more disorganized and more permeable stratum corneum, such as seen with involved substitutes. The results suggest that uninvolved substitutes could demonstrate characteristics associated with both normal or involved psoriatic skins.

A comparative study between human skin substitutes and normal human skin using Raman microspectroscopy.

Research in the field of bioengineered skin substitutes is motivated by the need to find new dressings for people affected by skin injuries (burns, diabetic ulcers), and to develop adequate skin models to test new formulations developed in vitro. Thanks to advances in tissue engineering, it is now possible to produce human skin substitutes without any exogenous material, using the self-assembly method developed by the Laboratoire d'Organogénèse Expérimentale. These human skin substitutes consist of a dermis and a stratified epidermis (stratum corneum and living epidermis). Raman microspectroscopy has been used to characterize and compare the molecular organization of skin substitutes with normal human skin. Our results confirm that the stratum corneum is a layer rich in lipids which are well ordered (trans conformers) in both substitutes and normal human skin. The amount of lipids decreases and more gauche conformers appear in the living epidermis in both cases. However, the results also show that there are fewer lipids in the substitutes and that the lipids are more organized in the normal human skin. Concerning the secondary structure of proteins and protein content, the data show that they are similar in the substitutes and in the normal human skin. In fact, the epidermis is rich in α-keratin, whereas the dermis contains mainly type I collagen.

Yeast hnRNP-related proteins contribute to the maintenance of telomeres.

Telomeres protect the ends of linear chromosomes, which if eroded to a critical length can become uncapped and lead to replicative senescence. Telomerase maintains telomere length in some cells, but inappropriate expression facilitates the immortality of cancer cells. Recently, proteins involved in RNA processing and ribosome assembly, such as hnRNP (heterogeneous nuclear ribonucleoprotein) A1, have been found to participate in telomere maintenance in mammals. The Saccharomyces cerevisiae protein Npl3 shares significant amino acid sequence similarities with hnRNP A1. We found that deleting NPL3 accelerated the senescence of telomerase null cells. The highly conserved RNA recognition motifs (RRM) in Npl3 appear to be important for preventing faster senescence. Npl3 preferentially binds telomere sequences in vitro, suggesting that Npl3 may affect telomeres directly. Despite similarities between the two proteins, human hnRNP A1 is unable to complement the lack of Npl3 to rescue accelerated senescence in tlc1 npl3 cells. Deletion of CBC2, which encodes another hnRNP-related protein that associates with Npl3, also accelerates senescence. Potential mechanisms by which hnRNP-related proteins maintain telomeres are discussed.

Antipsoriatic drug development: challenges and new emerging therapies.

Psoriasis is a chronic recurring skin disorder affecting up to 2% of the world's population. Psoriatic lesions are generally visible, leading to significant emotional and social disabilities for patients. In the context of psoriasis, the orchestrated interplay between activated T cells, antigen-presenting cells and keratinocytes leads to the release of proinflammatory cytokines, chemokines and chemical mediators responsible for the perpetuation of this disease. Even though some therapies are available for psoriasis treatment, there is still no cure for this skin disorder and psoriatic patients are significantly unsatisfied, as demonstrated by recent worldwide surveys. Unlike other diseases, psoriasis does not have a generally accepted animal model, which complicates the successful introduction of new antipsoriatic drugs into clinical phases of development. Moreover, psoriasis affects infants, children and elderly patients which require long-term therapies. Thus, the development of new therapeutic approaches should consider multiple factors such as efficacy, dosing frequency, route of administration, toxicity as well as co-morbidities of patients. This article analyzes current challenges for the antipsoriatic drug development and reviews recent patent applications gathered from 2000 to 2011 for psoriasis treatment. Additionally, future perspectives for antipsoriatic drug development are summarized.

Effects of retinoic acid on keratinocyte proliferation and differentiation in a psoriatic skin model.

Psoriasis is a skin disease characterized by the presence of red plaques on the skin. This pathology is well-known to be a retinoid-sensitive disease. Previous investigations have shown that retinoids can modulate epidermal proliferation with an antiproliferative potential in hyperproliferative skins. The aim of this study was to compare the development of psoriatic substitutes cultured in a retinoic acid supplemented medium with those cultured in medium receiving no supplement, to define the effects of this growth factor on keratinocyte proliferation and differentiation. The self-assembly method was used to create substitutes. Characterization of the psoriatic substitutes was performed by histological and immunolabeling analyses. Results showed that psoriatic keratinocyte substitutes cultured with retinoic acid have a thinner epidermis compared with psoriatic keratinocyte substitutes cultured without this supplement. Further, the expression of all tested cell differentiation markers was restored in psoriatic keratinocyte substitutes cultured in presence of retinoic acid. No significant change in epidermal thickness or in the expression of late differentiation markers was observed in healthy keratinocyte substitutes cultured with or without retinoic acid; however, some changes were reported for proliferation and early differentiation markers. Results suggest that retinoic acid can modulate epidermal differentiation and proliferation with an antiproliferative potential in psoriatic substitutes such as observed in psoriatic skin in vivo.

Effects of serum-free culture at the air-liquid interface in a human tissue-engineered skin substitute.

Previous studies have reported that well-defined culture conditions can improve keratinocytes terminal differentiation and reproducibility. The aim of our study was to compare skin substitutes cultured in a complete medium with those cultured in a serum-free medium at the air-liquid interface to optimize the self-assembly method. Skin substitutes, cultured in a serum-free medium over 7, 14, and 21 days, were compared with others cultured in a complete medium (5% serum) over the complete culture period. Masson's Trichrome staining showed that the substitutes cultured in a serum-free medium generated a well-developed and differentiated epidermis. Immunolabeling analyses between the substitutes cultured without serum and those cultured in complete serum showed similar expression of epidermal differentiation markers, dermo-epidermal junction, and dermal extracellular matrix components. On the basis of our Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) results, the skin substitutes cultured in serum-free condition over 21 days of culture at the air-liquid interface showed lower frequencies of the CH(2) symmetric mode of vibrations, which means a better lipid organization of the stratum corneum. No significant difference in hydrocortisone penetration was observed between serum-free medium substitutes and the controls. Results demonstrate that the absence of serum does not compromise the characteristics of the skin substitutes observed in this study.

Development of an in vitro psoriatic skin model by tissue engineering.

BACKGROUND: Psoriasis is a chronic skin disease characterized by a thickening and disorganization of the skin's protective barrier. OBJECTIVES: This study aims to develop and characterize a novel in vitro psoriatic human skin model produced by tissue engineering. METHODS: The self-assembly method, a tissue engineering approach based on the capacity of mesenchymal cells, such as fibroblasts, to create their own extracellular matrix in vitro, was used to create our substitutes. Manipulatable sheets of fibroblasts were superimposed creating a new dermis upon which keratinocytes are seeded, leading to a complete bilayered skin substitute. The characterization of the psoriatic substitutes was performed by macroscopic, histological and immunohistochemical analyses and contrasted to those constructed from healthy cells. RESULTS: Macroscopically, the psoriatic substitutes were more white and thicker than the healthy substitutes. The histological analysis of psoriatic substitutes stained with Masson's trichrome revealed a characteristic thickening of the epidermal layer seen in psoriatic skin in vivo. Immunohistochemical analysis of the psoriatic substitutes showed, among other things, an overexpression of involucrin and an underexpression of filaggrin and loricrin. CONCLUSION: These data suggest that the macroscopic, histological and immunohistochemical characteristics of psoriasis are partially retained in the substitutes, thus providing a good model to investigate the mechanisms of abnormal keratinocyte growth and to study cell-cell interactions.