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Background: The optimal therapy for deep burn wounds is based on the early debridement of necrotic tissue followed by wound coverage to avoid a systemic inflammatory response and optimize scar-free healing. The outcomes are affected by available resources and underlying patient factors, which represent challenges in burn care and suboptimal outcomes. In this study, we aimed to determine optimal burn-wound management using enzymatic debridement (NexoBrid™, MediWound Germany GmbH, Rüsselsheim, Germany) and intact fish skin (Kerecis® Omega3 Wound, Isafjordur, Iceland). Methods: In this retrospective case series, 12 patients with superficial or deep dermal burn wounds were treated with enzymatic debridement followed by fish skin, Suprathel® (PolyMedics Innovations GmbH, Denkendorf, Germany), or a split-thickness skin graft (STSG). Patients’ outcomes regarding healing and scar quality were collected objectively and subjectively for 12 months after the burn injury. Results: Wounds treated with fish skin demonstrated accelerated wound healing, a significantly higher water-storage capacity, and better pain relief. Furthermore, improved functional and cosmetic outcomes, such as elasticity, skin thickness, and pigmentation, were demonstrated. The pain and itch expressed as POSAS scores (Patient and Observer Scar Assessment Scale) for fish skin decreased compared to those for wounds managed with an STSG or Suprathel. Importantly, fish skin-treated wounds had significantly improved sebum production and skin elasticity than those treated with Suprathel but showed no significant superiority compared to STSG-treated wounds. Conclusions: Enzymatic debridement in combination with intact fish skin grafts resulted in the faster healing of burn wounds and better functional and aesthetic outcomes than split-thickness skin grafts and Suprathel treatment.

Background and Aims Much literature evidence points towards an essential role of mitochondrial quality control mechanisms in acute kidney injury progression. Renal ischemic-reperfusion injury (IRI) results in metabolic adaptation of proximal tubule epithelial cells, a site of high mitochondrial turnover (1). Moreover, exacerbation of renal injury has been demonstrated following IRI in both PTEN-induced kinase 1 (PINK1) knockout and Parkin knockout mice (2). The identification of a single point mutation (m.547A>T) within the mitochondrial genome of a large pedigree of patients with maternally-inherited tubulointerstitial kidney disease, highlights the importance of mitochondrial integrity in human renal pathophysiology (3). USP30 is a mitochondrial associated deubiquitylating enzyme that acts on the mitochondrial import receptor subunit TOM20 to repress PINK1/Parkin-mediated mitophagy and modulate mitochondrial protein transport (4,5). Within kidney, USP30 expression is predominantly tubular and accordingly, USP30 inhibition may provide a mechanism to protect against IRI. MTX008 is a selective small molecule inhibitor of USP30. Prophylactic administration of MTX008 15 mg/kg (p.o.) BID has shown robust and reproducible efficacy in a mouse model of IRI-induced kidney fibrosis (6). Here we present data showing that dosing MTX008 15 mg/kg (p.o.) BID in a therapeutic paradigm, also results in efficacy in the same IRI-induced kidney fibrosis model. Method On Day 0 (zero) C57BL/6 mice were anaesthetized, and their left renal pedicle was clamped transiently for 45 min, causing circulatory arrest in the kidney with consecutive IRI. Mice were then administered either vehicle or MTX008 15 mg/kg (p.o.) BID for 21 days, with first treatment starting five hours following IRI surgery (i.e. therapeutics dosing). Mice were monitored and kidneys harvested at Day +21. Kidney sections were quantitatively assessed for relative cellular morphology, fibrosis and macrophage infiltration using blinded histological scoring methods. Results Body weight was similar between groups and remained constant throughout the observation periods. Masson trichrome staining revealed significantly less tubular atrophy in MTX008 treated animals on Day +21. Similarly, fibronectin expression and macrophage infiltration in the cortex was also significantly reduced in MTX008 treated mice on Day +21. Conclusion MTX008, a novel selective small molecule inhibitor of USP30 has shown efficacy in a model of IR-induced CKD when dosed therapeutically. Initiating treatment after the establishment of IRI has shown significant benefits towards reduced progression to CKD with less tubular atrophy and renal fibrosis. Mission Therapeutics is investigating MTX008 in a variety of preclinical renal injury models with a view to developing this novel molecule towards the clinic. Therapeutic dosing opens a new and attractive opportunity for the treatment of AKI and sets our UPS30 inhibitor apart from other molecules currently in development.

Background and Aims Diclofenac is frequently used for pain control. In a previous study, we showed that already a single oral dose of diclofenac could reduce renal perfusion in healthy individuals. To investigate the influence of oral diclofenac administration on renal inflammation in the setting of pre-existing renal damage, we used a mouse model of subclinical acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (IRI) followed by diclofenac administration. Method Male CD1 mice (7-8 weeks old) underwent unilateral renal pedicle clamping for 15min to induce subclinical AKI. After reperfusion mice received a single oral dose of 100 or 200mg/kg diclofenac via oral gavage. Vehicle treated mice with unilateral IRI served as control. At day 1, mice were placed into metabolic cages to collect urine. Histology was performed on day 1 and 14 for renal morphology. Inflammation and fibrosis were investigated by immunohistochemistry and qPCR. Results Diclofenac treated mice showed reduced urine production. Morphologically, signs of AKI were more pronounced in diclofenac treated kidneys which also showed more Cox-2 positive tubuli in the cortex. On mRNA expression level the pro-inflammatory markers IL-6 and CXCL2, the chemoattractant for neutrophils, were elevated in the diclofenac group. Early upregulation of the pro-fibrotic markers CTGF and PAI-1 was detected already on d1 after IRI in the diclofenac group and tubular atrophy was pronounced after two weeks. Conclusion Already, a single oral dose of diclofenac causes aggravation of renal inflammation and progressive renal fibrosis in the setting of pre-existing subclinical acute kidney injury.

This photovoice project was undertaken by the Family Advisory Committee of the Canada Fetal Alcohol Spectrum Disorder (FASD) Research Network to describe the experiences and the challenges faced by those supporting loved ones with FASD. Photovoice is a method of bringing forth the voice of those who are typically marginalized. It is a process by which people can act as recorders and potential catalysts for social action and change. The Family Advisory Committee chose the photovoice technique to communicate both their experiential knowledge and the research knowledge on both the challenges and rewards in supporting individuals with FASD. This photovoice project highlights several themes that are consistent with the results of caregiver research and provide a glimpse into the experience of those supporting loved ones with FASD. Through this type of knowledge translation the Family Advisory Committee hopes to enhance policy maker and service provider understanding of the necessity of providing support and services not only to the individual with FASD but to those who support them as well.

Rational design and elaborate modular construction of interfacial architectures in which molecular transport is mediated by responsive/adaptive nanostructures has become a growing and fertile field of research in supramolecular materials chemistry. This work presents, for the first time, the use of PNIPAM-capped mesoporous silica thin films as thermosensitive cation-selective mesochannels. Thus far, this feature has only been observed in thermosensitive biological channels. The interfacial architecture created here accomplishes its specific functions through the concerted or simultaneous action of spatially addressed subunits with temperature response and ion exclusion capabilities. The thermo-perm-selectivity effect stems from the synergistic interplay between the pH-dependent electrostatic characteristics of the silica scaffold and the thermo-controlled steric effects introduced by the capping brush layer. It is hoped that the ?nanoarchitectonic? approach presented here will provide new routes toward the generation of heterosupramolecular nanosystems displaying addressable transport properties similar to those encountered in biological ion channels. Fil: Schmidt, Sonja. Universität Göttingen; Alemania Fil: Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Vana, Philipp. Universität Göttingen; Alemania Fil: Soler Illia, Galo Juan de Avila Arturo. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Azzaroni, Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina

How rainfall infiltration rate and soil hydrological characteristics develop over time under forests of different ages in temperate regions is poorly understood. In this study, infiltration rate and soil hydrological characteristics were investigated under forests of different ages and under grassland. Soil hydraulic characteristics were measured at different scales under a 250-year-old grazed grassland (GL), 6-year-old (6yr) and 48-year-old (48yr) Scots pine (Pinus sylvestris) plantations, remnant 300-year-old individual Scots pine (OT) and a 4000-year-old Caledonian Forest (AF). In situ field-saturated hydraulic conductivity (Kfs) was measured, and visible root:soil area was estimated from soil pits. Macroporosity, pore structure and macropore connectivity were estimated from X-ray tomography of soil cores, and from water-release characteristics. At all scales, the median values for Kfs, root fraction, macroporosity and connectivity values tended to AF > OT > 48yr > GL > 6yr, indicating that infiltration rates and water storage increased with forest age. The remnant Caledonian Forest had a huge range of Kfs (12 to >4922 mm h−1), with maximum Kfs values 7 to 15 times larger than those of 48-year-old Scots pine plantation, suggesting that undisturbed old forests, with high rainfall and minimal evapotranspiration in winter, may act as important areas for water storage and sinks for storm rainfall to infiltrate and transport to deeper soil layers via preferential flow. The importance of the development of soil hydrological characteristics under different aged forests is discussed.