RESUMO
The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine (n = 23) and human (n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose-dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse (n = 8) and human (n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% (n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.
Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Camundongos , Animais , Acúmulo de Mutações , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Pele/patologia , Epiderme/patologia , Carcinoma Basocelular/patologia , Raios Ultravioleta/efeitos adversos , MutaçãoRESUMO
Dupilumab is currently the only biologic treatment approved for moderate-to-severe atopic dermatitis. Though limited, available clinical data describing dupilumab use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic treatment in pregnant women with atopic dermatitis is currently restricted to corticosteroids, cyclosporine A, and azathioprine. Atopic dermatitis often has a deleterious course in pregnancy which can cause substantial distress and significantly impact on global health and quality of life. We report a case of severe atopic dermatitis treated safely with dupilumab during pregnancy with no adverse maternal or fetal outcomes observed. Our case highlights that dupilumab use in pregnancy has its place but should always be preceded by careful assessment of the risks and benefits. Clinicians are encouraged to enroll their patients in relevant pregnancy registry studies to monitor outcomes in women exposed to dupilumab during pregnancy and lactation.
RESUMO
Laribacter hongkongensis, a recently discovered bacterium associated with community-acquired gastroenteritis, has been found in the intestines of freshwater fish. To better understand the epidemiology and ecology of the bacterium, we carried out a surveillance study to investigate possible seasonal variation in the recovery of L. hongkongensis and its distribution in various organs in retail freshwater fish in Hong Kong. Forty whole freshwater fish of two species (20 grass carps and 20 bighead carps), and intestines from 120 grass carps were sampled during a one-year period. L. hongkongensis was isolated from 11 (55%) of the 20 grass carps and 6 (30%) of the 20 bighead carps; and the intestines of 49 (41%) of 120 grass carps. Seasonal variation in the recovery of L. hongkongensis from both whole fish and intestines was observed, with higher isolation rates in spring and summer than in fall and winter. There was also positive correlation between temperature and the isolation rates. When L. hongkongensis was cultured in vitro at different temperatures, shorter lag time and higher growth rate were observed at higher temperatures, with 37 degrees C being optimal among the tested temperatures. L. hongkongensis was commonly found in the gills, stomachs and intestines in both grass carps and bighead carps, and on the skin surface of one fish, but not in other organs. Proper handling of freshwater fish for cooking, especially the gills and gut, is recommended to prevent acquisition of L. hongkongensis, and other freshwater fish related infections.