UVA1 induces the formation of 8-hydroxy-2'-deoxyguanosines (8-OH-dGs) and cyclobutane pyrimidine dimers (CPDs) in the cellular genome. However, the relative contribution of each type of damage to the in vivo genotoxicity of UVA1 has not been clarified. We irradiated living mouse skin with 364-nm UVA1 laser light and analyzed the DNA damage formation and mutation induction in the epidermis and dermis. Although dose-dependent increases were observed for both 8-OH-dG and CPD, the mutation induction in the skin was found to result specifically from the CPD formation, based on the induced mutation spectra in the skin genome: the dominance of C --> T transition at a dipyrimidine site. Moreover, these UV-specific mutations occurred preferentially at the 5'-TCG-3' sequence, suggesting that CpG methylation and photosensitization-mediated triplet energy transfer to thymine contribute to the CPD-mediated UVA1 genotoxicity. Thus, it is the CPD formation, not the oxidative stress, that effectively brings about the genotoxicity in normal skin after UVA1 exposure. We also found differences in the responses to the UVA1 genotoxicity between the epidermis and the dermis: the mutation induction after UVA1 irradiation was suppressed in the dermis at all levels of irradiance examined, whereas it leveled off from a certain high irradiance in the epidermis.

Converging evidence has shown the link between benign epilepsy with centrotemporal spikes (BECTS) and abnormal functional connectivity among distant brain regions. However, prior research in BECTS has not examined the dynamic changes in functional connectivity as networks form. We combined functional connectivity density (FCD) mapping and sliding windows correlation analyses, to fully capture the functional dynamics in patients with respect to the presence of interictal epileptic discharges (IEDs). Resting-state fMRI was performed in 43 BECTS patients and 28 healthy controls (HC). Patients were further classified into two subgroups, namely, IED (n = 20) and non-IED (n = 23) depending on the simultaneous EEG-fMRI recordings. The global dynamic FCD (dFCD) was measured using sliding window correlation. Then we quantified dFCD variability using their standard deviation. Compared with HC, patients with and without IEDs both showed invariable dFCD (decreased) among the orbital fontal cortex, anterior cingulate cortex and striatum, as well as variable dFCD (increased) in the posterior default mode network (P < 0.05, AlphaSim corrected). Correlation analysis indicated that the variable dFCD in precuneus was related to seizure onset age (P < 0.05, uncorrected). BECTS with IEDs showed variable dFCD in regions related to the typical seizure semiology. The abnormal patterns of fluctuating FCD in BECTS suggest that both active and chronic epileptic state may contribute to altered dynamics of functional connectivity associated with cognitive disturbances and developmental alterations. These findings highlight the importance of considering fluctuating dynamic neural communication among brain systems to deepen our understanding of epilepsy diseases.

Aim: Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. Methods: This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. Results: The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH < 7.00 occurred in 77.1% of patients with a decrease in fibrinogen levels to ≤ 250 mg/dL. Conclusion: Pre-delivery fibrinogen can predict adverse maternal as well as neonatal outcomes with placental abruption.

No abstract