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Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults). Methods: Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis. Results: Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents. Conclusions: Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.

Background: Necrotizing fasciitis (NF) is a serious infectious disease that can initially place the patient’s life in danger and, after successful surgical and antibiotic treatment, leaves extensive wounds with sometimes even exposed bones and tendons. Autologous skin grafts are not always possible or require adequate wound bed preparation. Novel intact fish skin grafts (iFSGs; Kerecis® Omega3 Wound, Kerecis hf, Isafjördur, Iceland) have already shown their potential to promote granulation in many other wound situations. Faster wound healing rates and better functional and cosmetic outcomes were observed due to their additionally postulated anti-inflammatory and analgesic properties. Therefore, iFSGs may also be essential in treating NF. We present our initial experience with iFSGs in treating leg wounds after NF and review the literature for the current spectrum of clinical use of iFSGs. Case Presentations: We present two male patients (aged 60 and 69 years) with chronic or acute postsurgical extensive leg ulcers six weeks and six days after necrotizing fasciitis, respectively. Both suffered from diabetes mellitus without vascular pathologies of the lower limbs. A single application of one pre-meshed (Kerecis® Graftguide) and one self-meshed 300 cm2 iFSG (Kerecis® Surgiclose) was performed in our operation room after extensive surgical debridement and single circles of negative wound pressure therapy. Application and handling were easy. An excellent wound granulation was observed, even in uncovered tibia bone and tendons, accompanied by pain relief in both patients. Neither complications nor allergic reactions occurred. The patients received autologous skin grafting with excellent functional and cosmetic outcomes. Conclusions: iFSGs have the potential to play a significant role in the future treatment of NF due to the fast promotion of wound granulation and pain relief. Our experience may encourage surgeons to use iFSGs in NF patients, although high-quality, large

GTP binding proteins known as small GTPases make up one of the largest groups of regulatory proteins and control almost all functions of living cells. Their activity is under, respectively, positive and negative regulation by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which together with their upstream regulators and the downstream targets of the small GTPases form formidable signalling networks. While genomics has revealed the large size of the GTPase, GEF and GAP repertoires, only a small fraction of their interactions and functions have yet been experimentally explored. Dictyostelid social amoebas have been particularly useful in unravelling the roles of many proteins in the Rac-Rho and Ras-Rap families of GTPases in directional cell migration and regulation of the actin cytoskeleton. Genomes and cell-type specific and developmental transcriptomes are available for Dictyostelium species that span the 0.5 billion years of evolution of the group from their unicellular ancestors. In this work, we identified all GTPases, GEFs and GAPs from genomes representative of the four major taxon groups and investigated their phylogenetic relationships and evolutionary conservation and changes in their functional domain architecture and in their developmental and cell-type specific expression. We performed a hierarchical cluster analysis of the expression profiles of the ~2000 analysed genes to identify putative interacting sets of GTPases, GEFs and GAPs, which highlight sets known to interact experimentally and many novel combinations. This work represents a valuable resource for research into all fields of cellular regulation.