Oleogel-S10 in Dystrophic Epidermolysis Bullosa: A Case Series Evaluating the Impact on Wound Burden Over Two Years.

Epidermolysis bullosa (EB) is a group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Impaired wound healing is central and can lead to serious clinical complications, deformities, and symptoms with a devastating impact on quality of life (QoL). Dressing changes and wound care are central to the management of EB. Recently Oleogel-S10 (also known as birch bark extract or birch triterpenes) was approved in Europe and the UK for treating EB wounds. This approval was based on data from the EASE phase 3 study, which demonstrated Oleogel-S10 accelerated wound healing, reduced total wound burden, and decreased the frequency of dressing changes in patients with EB. A retrospective analysis of medical records was conducted for up to 24 months in 13 patients with EB treated with Oleogel-S10 through an early access programme in Colombia. Effectiveness was assessed by measuring body surface area percentage (BSAP) and total body wound burden (EBDASI). Tolerability and safety were monitored throughout. This is the first report to evaluate the effectiveness of Oleogel-S10 in clinical practice. The results showed a reduction in percentage of BSA affected, from a mean of 27.3% at baseline to 10.4% at 24-month follow-up, despite treatment interruptions. A reduction in EBDASI skin activity score of - 16.2 (24 months) together with a reduced skin damage index score of - 15.4 (18 months) was also observed. Physicians, patients, and caregivers perceived faster wound closure. Adherence with therapy by patients was good, and patients expressed satisfaction with treatment and reported improvements in self-esteem, productivity, and social interaction. Oleogel-S10 was well tolerated; however, two patients reported worsening wounds related to gauze adherence. Two deaths during treatment interruption were reported and was not considered related to Oleogel-S10. This study supports the effectiveness of Oleogel-S10 in a real-world scenario in a country with scarce resources for the treatment of EB.

Genome-Wide Analysis of WRKY and NAC Transcription Factors in Carica papaya L. and Their Possible Role in the Loss of Drought Tolerance by Recent Cultivars through the Domestication of Their Wild Ancestors.

A genome-wide analysis for two families of key transcription factors (TF; WRKY and NAC) involved in drought response revealed 46 WRKY and 66 NAC members of the Carica papaya genome. A phylogenetic analysis grouped the CpWRKY proteins into three groups (I, II a, b, c, d, e and III), while the CpNAC proteins were clustered into 15 groups. The conserved domains, chromosomal localization and promoter cis-acting elements were also analyzed. In addition, from a previous transcriptome study of two contrasting genotypes in response to 14 days of water deficit stress (WDS), we found that 29 of the 46 CpWRKYs genes and 25 of the 66 CpNACs genes were differentially expressed in response to the WDS. In the present paper, the native wild genotype (WG) (collected in its center of origin) consistently showed a higher expression (transcripts per million; TPM and fold change; FC) than the commercial genotype (CG) in almost all the members of the CpWRKY and CpNAC gene families. To corroborate this, we selected CpWRKY50 and CpNAC83.1 for further evaluation by RT-qPCR. Consistently, the WG showed higher relative expression levels (REL) after 14 days of WDS than the CG, in both the leaves and roots. The results suggest that the CpWRKY and CpNAC TF families are important for drought tolerance in this species. The results may also suggest that, during the domestication process, the ability of the native (wild) C. papaya genotypes to respond to drought (including the overexpression of the CpWRKY and CpNAC genes) was somehow reduced in the current commercial genotypes.

Robotic Manipulation in Dynamic Scenarios via Bounding-Box-Based Hindsight Goal Generation.

By relabeling past experience with heuristic or curriculum goals, state-of-the-art reinforcement learning (RL) algorithms such as hindsight experience replay (HER), hindsight goal generation (HGG), and graph-based HGG (G-HGG) have been able to solve challenging robotic manipulation tasks in multigoal settings with sparse rewards. HGG outperforms HER in challenging tasks in which goals are difficult to explore by learning from a curriculum, in which intermediate goals are selected based on the Euclidean distance to target goals. G-HGG enhances HGG by selecting intermediate goals from a precomputed graph representation of the environment, which enables its applicability in an environment with stationary obstacles. However, G-HGG is not applicable to manipulation tasks with dynamic obstacles, since its graph representation is only valid in static scenarios and fails to provide any correct information to guide the exploration. In this article, we propose bounding-box-based HGG (Bbox-HGG), an extension of G-HGG selecting hindsight goals with the help of image observations of the environment, which makes it applicable to tasks with dynamic obstacles. We evaluate Bbox-HGG on four challenging manipulation tasks, where significant enhancements in both sample efficiency and overall success rate are shown over state-of-the-art algorithms. The videos can be viewed at https://videoviewsite.wixsite.com/bbhgg.

Purpura Fulminans Secondary to Streptococcus pneumoniae Meningitis.

Purpura fulminans (PF) is a rare skin disorder with extensive areas of blueblack hemorrhagic necrosis. Patients manifest typical laboratory signs of disseminated intravascular coagulation (DIC). Our case describes a 37-year-old previously healthy man who presented with 3 days of generalized malaise, headache, vomiting, photophobia, and an ecchymotic skin rash. Initial laboratory workup revealed DIC without obvious infectious trigger including unremarkable cerebrospinal fluid (CSF) biochemical analysis. There was further progression of the skin ecchymosis and multiorgan damage consistent with PF. Final CSF cultures revealed Streptococcus pneumoniae. Despite normal initial CSF biochemical analysis, bacterial meningitis should always be considered in patients with otherwise unexplained DIC as this may be an early manifestation of infection. PF is a clinical diagnosis that requires early recognition and prompt empirical treatment, especially, in patients with progressive altered mental status, ecchymotic skin rash, and DIC.