Solar ultraviolet A (UV-A) radiation promotes a huge variety of damages on connective tissues and dermal fibroblasts, including cellular senescence, a major contributor of skin photoaging. The mechanisms of skin photoaging evoked by UV-A partly involve the generation of reactive oxygen species and lipid peroxidation. We previously reported that 4-hydroxynonenal (HNE), a lipid peroxidation-derived aldehyde, forms adducts on elastin in the skins of UV-A irradiated hairless mice, possibly contributing to actinic elastosis. In the present study, we investigated whether and how HNE promotes fibroblast senescence in skin photoaging. Dermal fibroblasts of skins from UV-A-exposed hairless mice exhibited an increased number of γH2AX foci characteristic of cell senescence, together with an accumulation of HNE adducts partly colocalizing with the cytoskeletal protein vimentin. Murine fibroblasts exposed to UV-A radiation (two cycles of 15 J/cm²), or HNE (30 µM, 4 h), exhibited senescence patterns characterized by an increased γH2AX foci expression, an accumulation of acetylated proteins, and a decreased expression of the sirtuin SIRT1. HNE adducts were detected on vimentin in cultured fibroblasts irradiated by UV-A or incubated with HNE. The HNE scavenger carnosine prevented both vimentin modification and fibroblast senescence evoked by HNE in vitro and in the skins of UV-A-exposed mice. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in fibroblast senescence, and confirm the protective effect of carnosine in skin photoaging.

Introduction: To compare the maternal and neonatal outcomes associated with Instrumental Rotation (IR) to operative vaginal delivery in occiput posterior (OP) position with Thierry’s spatulas (TS), in the setting of failed manual rotation (MR). Study design: We led a prospective observational cohort study in a tertiary referral hospital in Toulouse, France. All women presenting in labor with persistent OP position at full cervical dilatation and who delivered vaginally after failed MR and with IR or OP assisted delivery were included from January 2014 to December 2015. The main outcomes measured were maternal morbidity parameters including episiotomy rate, incidence and severity of perineal lacerations, perineal hematomas and postpartum hemorrhage. Severe perineal tears corresponded to third and fourth degree lacerations. Fetal morbidity outcomes comprised neonatal Apgar scores, acidemia, fetal injuries, birth trauma and neonatal intensive care unit admissions. Results: Among 9762 women, 910 (9.3%) presented with persistent OP position at full cervical dilatation and 222 deliveries were enrolled. Of 111 attempted IR, 97 were successful (87.4%). The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.8% vs. 12.6%; p < 0.002). Both groups were similar regarding most fetal outcomes and no birth trauma occurred in our study population. In a multivariable logistic regression analysis, OP operative delivery was a significant risk factor of severe perineal lacerations (OR = 9.5; 95% CI: 2.05–44.05). Conclusion: Our results support the use of IR in order to reduce perineal morbidity associated with OP assisted delivery, in the setting of a failed manual rotation.