Erythrokeratodermia variabilis: report of two cases and a novel missense variant in GJB4 encoding connexin 30.3.

Erythrokeratodermia variabilis (EKV) is characterized by migrating red patches resembling a geographical map, and by localized or generalized hyperkeratosis with scaling of the skin. The onset is usually at birth or during infancy, and the disease persists throughout life. EKV is mainly inherited as an autosomal dominant disease, although recessive transmission has occasionally been reported. Mutations associated with EKV have been identified in the connexin (Cx) genes GJB3 (Cx31) and GJB4 (Cx30.3), however, several cases of EKV have been tested negative for mutations in these two Cx genes. Here, we report our findings of the clinical, histological, and molecular examinations performed in two unrelated sporadic cases of EKV. The molecular screening involved bidirectional sequencing of the coding regions of the GJB3 and GJB4 genes and revealed the existence of a novel c.295G>A missense variant in the GJB4 gene found in homozygosity in one case. The substitution was found to result in a p.E99K change of the Cx30.3 protein, an alteration predicted to have a benign rather than a damaging effect on the protein function.

Tacrolimus 0.1% vs mometasone furoate topical treatment in allergic contact hand eczema: a prospective randomized clinical study.

Tacrolimus is a macrolide immunosuppressant that has been demonstrated to inhibit T-lymphocyte activation without the side-effects of corticosteroids. The safety profile of tacrolimus makes it a promising therapeutic option for dermatitis. To evaluate and compare the therapeutic ability of tacrolimus 0.1% ointment and mometasone furoate 0.1% ointment in patients with chronic hand eczema and positive patch tests. Thirty adults with chronic hand eczema and positive patch test reaction to relevant contact allergens were treated with tacrolimus 0.1% ointment or mometasone furoate 0.1% ointment in a single-centre, randomized comparative study. The scores of the evaluated clinical parameters (erythema, infiltration, vesiculation, desquamation, presence of cracks and itching) did not differ between Groups A and B at any of the four time points (p>0.05).On the other hand, in both groups, a significant difference was detected in all parameters between baseline and Day 90 recorded values. Tacrolimus is a promising alternative therapy for contact dermatitis patients as it is effective from the first month of treatment, well tolerated and offers similar therapeutic results to topical corticosteroid therapy.

Long-term forecasting of internet backbone traffic.

We introduce a methodology to predict when and where link additions/upgrades have to take place in an Internet protocol (IP) backbone network. Using simple network management protocol (SNMP) statistics, collected continuously since 1999, we compute aggregate demand between any two adjacent points of presence (PoPs) and look at its evolution at time scales larger than 1 h. We show that IP backbone traffic exhibits visible long term trends, strong periodicities, and variability at multiple time scales. Our methodology relies on the wavelet multiresolution analysis (MRA) and linear time series models. Using wavelet MRA, we smooth the collected measurements until we identify the overall long-term trend. The fluctuations around the obtained trend are further analyzed at multiple time scales. We show that the largest amount of variability in the original signal is due to its fluctuations at the 12-h time scale. We model inter-PoP aggregate demand as a multiple linear regression model, consisting of the two identified components. We show that this model accounts for 98% of the total energy in the original signal, while explaining 90% of its variance. Weekly approximations of those components can be accurately modeled with low-order autoregressive integrated moving average (ARIMA) models. We show that forecasting the long term trend and the fluctuations of the traffic at the 12-h time scale yields accurate estimates for at least 6 months in the future.