The cellular and molecular microenvironment of epithelial stem and progenitor cells is poorly characterized despite well-documented roles in homeostatic tissue renewal, wound healing, and cancer progression. Here, we demonstrate that, in organotypic cocultures, dermal pericytes substantially enhanced the intrinsically low tissue-regenerative capacity of human epidermal cells that have committed to differentiate and that this enhancement was independent of angiogenesis. We used microarray analysis to identify genes expressed by human dermal pericytes that could potentially promote epidermal regeneration. Using this approach, we identified as a candidate the gene LAMA5, which encodes laminin α5, a subunit of the ECM component laminin-511/521 (LM-511/521). LAMA5 was of particular interest as we had previously shown that it promotes skin regeneration both in vitro and in vivo. Analysis using immunogold localization revealed that pericytes synthesized and secreted LAMA5 in human skin. Consistent with this observation, coculture with pericytes enhanced LM-511/521 deposition in the dermal-epidermal junction of organotypic cultures. We further showed that skin pericytes could also act as mesenchymal stem cells, exhibiting the capacity to differentiate into bone, fat, and cartilage lineages in vitro. This study suggests that pericytes represent a potent stem cell population in the skin that is capable of modifying the ECM microenvironment and promoting epidermal tissue renewal from non-stem cells, a previously unsuspected role for pericytes.

We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88% and 90%, and major molecular responses (MMRs) were 47% and 73%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n ‫؍‬ 60), MMR rates by 12 and 24 months were 55% and 77% compared with 32% and 53% in patients averaging less than 600 mg (P ‫؍‬ .037 and .016, respectively). Dose escalation was indicated for 17 patients before 12 months for failure to achieve, or maintain, major cytogenetic response at 6 months or CCR at 9 months but was only possible in 8 patients (47%

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by biological and clinical heterogeneity. The interleukin (IL)-1 superfamily is a group of innate cytokines that contribute to pathogenesis in many autoimmune diseases. IL-1β and IL-18 are two members that have been shown to play a role in murine lupus-like models, but their role in human SLE remains poorly understood. Here, IL-1β and IL-18 were quantified by enzyme-linked immunosorbent assay in the serum of healthy controls (HCs) and SLE patients from a prospectively followed cohort. Disease activity and organ damage were assessed using SLE disease activity index 2000 (SLEDAI-2K) and SLE damage index scores (SDI), respectively. 184 SLE patients (mean age 44.9 years, 91% female, 56% double-stranded deoxyribonucleic acid positive) were compared to 52 HC. SLE patients had median [IQR] SLEDAI-2K of 4 [2,6], and SDI of 1 [0–2]. Serum IL-18 levels were statistically significantly higher in SLE patients compared to HCs. Univariable linear regression analyses showed that patients with active renal disease or irreversible organ damage had statistically significantly elevated serum IL-18 levels. The association between serum IL-18 and active renal disease was confirmed in multivariable analysis after adjusting for ethnicity and organ damage. High baseline serum IL-18 levels were associated with organ damage at the subsequent visit. Serum IL-1β levels were not significantly elevated in SLE patients when compared to HCs and had no association with overall or organ-specific disease activity or organ damage in cross-sectional and longitudinal analyses. Our data suggest that serum IL-18 and IL-1β have different clinical implications in SLE, with IL-18 being potentially associated with active renal disease.

ObjectivesGiven the importance of adherence to combination antiretroviral therapy (cART) for the reduced morbidity and improved mortality of people living with HIV infection (PLWH), we set out to determine which of a number of previously investigated personal, socioeconomic, treatment-related and disease-related factors were independently associated with self-reported difficulty taking antiretroviral therapy (ART) in an Australian sample of PLWH. MethodsUsing data from a national cross-sectional survey of 1106 PLWH, we conducted bivariate and multivariable analyses to assess the association of over 70 previously investigated factors with selfreported difficulty taking ART. Factors that maintained an association with reported difficulty taking ART at the level of a 5 0.05 in the multivariable logistic regression analysis were considered to be independently associated with reported difficulty taking ART. ResultsA total of 867 (78.4%) survey respondents were taking antiretroviral medication at the time of completing the HIV Futures 6 survey. Overall, 39.1% of these respondents reported difficulty taking ART. Factors found to be independently associated with reported difficulty taking ART included younger age, alcohol and party drug use, poor or fair self-reported health, diagnosis of a mental health condition, living in a regional centre, taking more than one ART dose per day, experiencing physical adverse events or health service discrimination, certain types of ART regimen and specific attitudes towards ART and HIV. ConclusionsThirteen previously investigated factors were found to be independently associated with reported difficulty taking ART, reaffirming the dynamic nature of adherence behaviour and the ongoing importance of addressing adherence behaviour in the clinical management of PLWH.Keywords: adherence, antiretroviral therapy, Australia, HIV, nonadherence IntroductionCombination antiretroviral therapy (cART) has revolutionized the course of HIV disease, transforming HIV infection from a life-threatening infection to a manageable chronic condition, particularly in developed countries [1][2][3]. However, a key challenge is the high level of adherence to cART that is required for viral suppression, immunological response and reduced morbidity and mortality in individuals with HIV/AIDS [4][5][6]. Studies have demonstrated a requirement for adherence levels of at least 95% in order to achieve adequate viral suppression for regimens including unboosted protease inhibitor (PI) therapy [4,7]. While a lower level of adherence has been shown to lead to viral suppression when using nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens [7], the development of treatment-resistant mutations has been shown to peak at approximately 70% adherence and there is an ongoing decline in the rate of developing treatmentresistant mutations towards 100% adherence, providing a DOI: 10.1111/j.1468-1293.2011.00928.x HIV Medicine (2011 r 2011 British HIV Association 562 further imperative for achieving near-perfect adhere...