Human Infections by Wohlfahrtiimonas chitiniclastica: A Mini-Review and the First Report of a Burn Wound Infection after Accidental Myiasis in Central Europe

Wohlfahrtiimonas chitiniclastica are bacteria that cause rare infections, typically associated with the infestation of an open wound with fly larvae. Here, we present a unique case report of the first W. chitiniclastica isolation from a burn wound with accidental myiasis in a 63-year-old homeless man and a literature review focused on human infections caused by these bacteria. So far, 23 cases of infection with W. chitiniclastica have been reported; in 52% of these, larvae were found in the wound area. Most of these cases suffered from chronic non-healing wound infections but none of these were burn injuries. The overall fatality rate associated directly with W. chitiniclastica in these cases was 17%. Infections with parasitic larvae occur in moderate climates (especially in people living in poor conditions); therefore, an infection with rare bacteria associated with accidental myiasis, such as W. chitiniclastica, can be expected to become more common there. Thus, in view of the absence of recommendations regarding the treatment of patients with accidental myiasis and, therefore, the risk of infection with W. chitiniclastica or other rare pathogens, we provide a list of recommendations for the treatment of such patients. The importance of meticulous microbial surveillance using molecular biological methods to facilitate the detection of rare pathogens is emphasized

Trichoderma longibrachiatum and Aspergillus fischeri Infection as a Cause of Skin Graft Failure in a Patient with Critical Burns after Liver Transplantation

Infectious complications are responsible for the majority of mortalities and morbidities of patients with critical burns. Although bacteria are the predominant etiological agents in such patients, yeasts and fungi have become relatively common causes of infections over the last decade. Here, we report a case of a young man with critical burns on 88% TBSA (total body surface area) arising as a part of polytrauma. The patient's history of orthotopic liver transplantation associated with the patient's need to use combined immunosuppressant therapy was an additional complication. Due to deep burns in the forearm region, we have (after a suitable wound bed preparation) applied a new bi-layered dermal substitute. The patient, however, developed a combined fungal infection in the region of this dermal substitute caused by Trichoderma longibrachiatum and Aspergillus fischeri (the first case ever reported). The infection caused the loss of the split-thickness skin grafts (STSGs); we had to perform repeated hydrosurgical and mechanical debridement and a systemic antifungal treatment prior to re-application of the STSGs. The subsequent skin transplant was successful

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 x 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.O

Antimicrobial Cost-Effective Transparent Hydrogel Films from Renewable Gum Karaya/Chitosan Polysaccharides for Modern Wound Dressings

The newest trends in wound healing management and the development of the next generation of dressings are pointing toward natural polymeric materials with important beneficial properties such as antimicrobial effects, renewability, easier process of preparation, and biological activity. Here, we present the preparation and in vitro evaluation of a unique biopolymeric blend composed of natural polymers based on the positively charged polysaccharide chitosan and negatively charged gum karaya. A plate lysis assay of gum karaya and chitosan solution mixtures proved the synergistic antimicrobial effect against specific strains of both Gram-positive and Gram-negative bacteria and yeast. This polymeric mixture was used for hydrogel film preparation and determination of the composition effect on physical properties (swelling behavior in different solvents, pH, diffusion mechanism, hydrolytic stability, mechanical and optical properties). While the pure gum karaya with poly(vinyl alcohol) exhibited the highest hydrolytic degradation (68%), the mixture of poly(vinyl alcohol) and gum karaya with chitosan (in the 25:75 ratio) exhibited the lowest degradation value (41%) due to the strong physical interactions. Cytotoxicity tests performed with hydrogel extracts using two different in vitro models, adherent fibroblasts (NIH3T3) and non-adherent suspension B-lymphocytes (BaF3), exhibited excellent biocompatibility and no cytotoxicity. As expected, the antimicrobial activity of 3-day film extracts showed a significantly improved antimicrobial effect of mixtures involving a chitosan biopolymer. The physical and biological properties of prepared biopolymer-based hydrogels meet the requirements of modern wound dressings

Clozapine Reverses Dysfunction of Glutamatergic Neurons Derived From Clozapine-Responsive Schizophrenia Patients

The cellular pathology of schizophrenia and the potential of antipsychotics to target underlying neuronal dysfunctions are still largely unknown. We employed glutamatergic neurons derived from induced pluripotent stem cells (iPSC) obtained from schizophrenia patients with known histories of response to clozapine and healthy controls to decipher the mechanisms of action of clozapine, spanning from molecular (transcriptomic profiling) and cellular (electrophysiology) levels to observed clinical effects in living patients. Glutamatergic neurons derived from schizophrenia patients exhibited deficits in intrinsic electrophysiological properties, synaptic function and network activity. Deficits in K+ and Na+ currents, network behavior, and glutamatergic synaptic signaling were restored by clozapine treatment, but only in neurons from clozapine-responsive patients. Moreover, neurons from clozapine-responsive patients exhibited a reciprocal dysregulation of gene expression, particularly related to glutamatergic and downstream signaling, which was reversed by clozapine treatment. Only neurons from clozapine responders showed return to normal function and transcriptomic profile. Our results underscore the importance of K+ and Na+ channels and glutamatergic synaptic signaling in the pathogenesis of schizophrenia and demonstrate that clozapine might act by normalizing perturbances in this signaling pathway. To our knowledge this is the first study to demonstrate that schizophrenia iPSC-derived neurons exhibit a response phenotype correlated with clinical response to an antipsychotic. This opens a new avenue in the search for an effective treatment agent tailored to the needs of individual patients

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased ( \u3c 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased ( \u3c 0.05) the expression of the CCR5 gene (day 3) and tended ( \u3e 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment