Keratinocytes Counteract UVB-Induced Immunosuppression in Mice through HIF-1a Signaling.

The transcription factor HIF-1a regulates cellular metabolism under hypoxia but also immune responses and UVB-induced skin reactions. In keratinocytes (KCs), HIF-1a is an environmental sensor orchestrating the adaptation to environmental changes. In this study, we investigated the role of HIF-1a in KCs for skin reactions to acute and chronic UVB exposure in mice. The function of HIF-1a in KCs under UVB exposure was analyzed in KC-specific HIF-1a conditional knockout (cKO) mice. cKO mice were hypersensitive to acute high-dose UVB irradiation compared with wild-type mice, displaying increased cell death and delayed barrier repair. After chronic low-dose UVB treatment, cKO mice also had stronger epidermal damage but reduced infiltration of dermal macrophages and T helper cells compared with wild-type mice. Irradiated cKO mice revealed accumulation of regulatory lymphocytes in dorsal skin-draining lymph nodes compared with wild-type and unirradiated mice. This was reflected by an augmented IL-10 release of lymph node cells and a weaker contact hypersensitivity reaction to DNFB in UVB-exposed cKO mice than in wild-type and unirradiated controls. In summary, we found that KC-specific HIF-1a expression is crucial for adaptation to UVB exposure and inhibits the development of UVB-induced immunosuppression in mice. Therefore, HIF-1a signaling in KCs could ameliorate photoaging-related skin disorders.

Environmental and individual factors affecting menu labeling utilization: a qualitative research study.

Obesity is a prominent public health concern that disproportionally affects low-income and minority populations. Recent policies mandating the posting of calories on menus in fast-food chain restaurants have not proven to uniformly influence food choice. This qualitative research study used focus groups to study individual and environmental factors affecting the use of these menu labels among low-income minority populations. Ten focus groups targeting low-income residents (n=105) were held at various community organizations throughout New York City over a 9-month period in 2011. The focus groups were conducted in Spanish, English, or a combination of both languages. In late 2011 and early 2012, transcripts were coded through the process of thematic analysis using Atlas.ti for naturally emerging themes, influences, and determinants of food choice. Few participants used menu labels, despite awareness. The most frequently cited as barriers to menu label use included: price and time constraints, confusion and lack of understanding about caloric values, as well as the priority of preference, hunger, and habitual ordering habits. Based on the individual and external influences on food choice that often take priority over calorie consideration, a modified approach may be necessary to make menu labels more effective and user-friendly.

Assessing the effect of food exposure on children's identification and acceptance of fruit and vegetables.

Currently, fewer than 15% of children between the ages of 4-8 years consume the recommended levels of fruit and vegetables. In order to address this serious public health issue, a variety of nutrition programs have been implemented across the United States which have varied in their success. The present research analyzed the effectiveness of providing fruit and vegetable exposure as part of a school nutrition program. Kindergarten students at two schools (N=59) were exposed to interactive activities about healthy eating and physical activity. In addition, those at one school (n=29) were exposed to a variety of fruits and vegetables as part of this program. Assessment of children's ability to identify and their willingness to try fruit and vegetables before and after the program indicated that while all children were better able to identify a range of fruit, only those who received exposure to healthful foods were more willing to try fruit after the program. There were no changes in their identification or willingness to eat vegetables. These results suggest that schools should provide exposure to a variety of healthy foods as part of their nutrition programs. Such programs should focus specifically on exposing children to vegetables because increasing children's willingness to try foods that are typically considered unpalatable may be especially challenging.

The effect of genetic polymorphisms in the vinyl chloride metabolic pathway on mutagenic risk.

Vinyl chloride (VC) is a human carcinogen known to undergo metabolism by cytochrome P450 2E1 (CYP2E1) to reactive intermediates that can cause oncogene and tumor suppressor gene mutations and that are further metabolized by acetaldehyde dehydrogenase (ALDH2) and glutathione-S-transferases (GSTs) to non-mutagenic end products. These metabolic enzymes have known polymorphisms that could lead to increased levels of the VC reactive intermediates and thus an increased risk for mutations and cancer following exposure. Using restriction fragment length polymorphism (RFLP) analysis, we have examined a cohort of 597 French VC workers for polymorphisms in CYP2E1, ALDH2, GSTM1 and GSTT1 in relation to the occurrence of mutant oncogene and tumor suppressor gene biomarkers that are attributable to VC exposure. The presence of the biomarkers for mutant ras-p21 and mutant p53 was found to be highly significantly associated with cumulative VC exposure (P for trend <0.0001). The presence of the CYP2E1 variant c2 allele was found to be significantly associated with the presence of either or both mutant biomarkers even after controlling for potential confounders including cumulative VC exposure (OR = 2.3, 95% CI = 1.2-4.1), and the effects of the c2 allele and VC exposure were approximately additive. GSTT1 null status was found to have an increased, but not significant association with the presence of either or both biomarkers after controlling for confounders (OR = 1.3, 95% CI = 0.8-2.0). These results suggest the existence of a possible gene-environment interaction between polymorphisms in the VC metabolic pathway and VC exposure that could contribute to the variable susceptibility to the mutagenic effects of VC in exposed populations.