The effect of 222-nm UVC phototesting on healthy volunteer skin: a pilot study.

BACKGROUND: Frequent topical antiseptic use to hands is now common in healthcare and other work environments. Inevitably, the use of such antiseptics will present an occupational risk for irritancy and allergic dermatitis. New, less irritant and even non-chemical antimicrobial approaches are under investigation. METHODS: A Sterilray disinfectant source (222 nm) conventionally used to sterilize equipment and work surfaces was assessed for tolerability in human skin. Using an escalating dosage study methodology, four skin phototype I and II healthy volunteers had their minimal erythema dose (MED) determined. Punch biopsies of irradiated sites were stained for cyclobutane pyrimidine dimers (CPD). The degree of CPD was compared with that in biopsies from unexposed skin and from areas exposed to UVB (280-315 nm) radiation. RESULTS: Calibrated spectral measurements revealed emission at a peak wavelength of 222 nm with 97% emission at wavelengths less than 250 nm. At low doses below the threshold bacteriostatic effect, the source was capable of inducing both erythema and CPD formation in human skin. In two individuals, cells in the basal layer were not shielded by the overlying tissue as indicated by the presence of CPD. CONCLUSION: The source showed an erythemogenic or CPD potential at lower doses than those required to reach the reported threshold bacteriostatic effect.

The Microevolution and Epidemiology of Staphylococcus aureus Colonization during Atopic Eczema Disease Flare.

Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. A characteristic of atopic eczema (AE) is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the microevolution of S. aureus colonization, we deep sequenced S. aureus populations from nine children with moderate to severe AE and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE patients and control participants, with all but one of the individuals carrying colonies belonging to a single sequence type. Phylogenetic analysis showed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE cases versus controls (Fisher exact test, P = 0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.

Differential contextual responses of normal human breast epithelium to ionizing radiation in a mouse xenograft model.

Radiotherapy is a key treatment option for breast cancer, yet the molecular responses of normal human breast epithelial cells to ionizing radiation are unclear. A murine subcutaneous xenograft model was developed in which nonneoplastic human breast tissue was maintained with the preservation of normal tissue architecture, allowing us to study for the first time the radiation response of normal human breast tissue in situ. Ionizing radiation induced dose-dependent p53 stabilization and p53 phosphorylation, together with the induction of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was stabilized in both luminal and basal cells, induction of Ser392-phosphorylated p53 and p21 was higher in basal cells and varied along the length of the ductal system. Basal breast epithelial cells expressed ΔNp63, which was unchanged on irradiation. Although stromal responses themselves were minimal, the response of normal breast epithelium to ionizing radiation differed according to the stromal setting. We also demonstrated a dose-dependent induction of γ-H2AX foci in epithelial cells that was similarly dependent on the stromal environment and differed between basal and luminal epithelial cells. The intrinsic differences between human mammary cell types in response to in vivo irradiation are consistent with clinical observation that therapeutic ionizing radiation is associated with the development of basal-type breast carcinomas. Furthermore, there may be clinically important stromal-epithelial interactions that influence DNA damage responses in the normal breast. These findings demonstrate highly complex responses of normal human breast epithelium following ionizing radiation exposure and emphasize the importance of studying whole-tissue effects rather than single-cell systems.