Search Results (427)

Background/Objectives: The clinical potential of antimicrobial peptides (AMPs) against dual threats like antimicrobial resistance (AMR) and cancer is often limited by their high host cell toxicity. Here, we focused on brevinin-2OS (B2OS), a novel peptide from the skin of Odorrana schmackeri with potent haemolytic activity. The objective was to study the structure–activity relationship and optimise the safety via targeted modifications. Methods: A dual-modification strategy involving C-terminal truncation and subsequent N-terminal D-amino acid substitution was employed. The bioactivities and safety profiles of the resulting analogues were evaluated using antimicrobial, haemolysis, and cytotoxicity assays. Result: Removal of the rana box in B2OS(1-22)-NH₂ substantially reduced haemolysis while maintaining bioactivities. Remarkably, the D-leucine substitution in [D-Leu²]B2OS(1-22)-NH₂ displayed a superior HC₅₀ value of 118.1 µM, representing a more than ten-fold improvement compared to its parent peptide (HC₅₀ of 10.44 µM). This optimised analogue also demonstrated faster bactericidal kinetics and enhanced membrane permeabilisation, leading to a greater than 22-fold improvement in its therapeutic index against Gram-positive bacteria. Conclusions: The C-terminal rana box is a primary determinant of toxicity rather than a requirement for activity in the B2OS scaffold. The engineered peptide [D-Leu²]B2OS(1-22)-NH₂ emerges as a promising lead compound, and this dual-modification strategy provides a powerful design principle for developing safer, more effective peptide-based therapeutics. Full article

Introduction: Biodegradable Temporizing Matrix (BTM) is a new synthetic dermal substitute suitable for wound closure and tissue regeneration. The data in paediatric population remain limited. The study purpose is to review the indications for BTM application in paediatric patients, evaluate the short-term and long-term results, including complications and functional outcomes, as well as to share some unique observations regarding the use of BTM in paediatric population. Patients and Methods: Patients undergoing reconstructive surgery and BTM application during the last three years were included. Data collected included patient demographics, primary diagnosis, previous surgical management, post-operative complications and final outcomes. BTM was used in 32 patients. The indications varied including epidermolysis bullosa (n = 6), burns (n = 4), trauma (n = 7), infection (n = 4), ischemia or necrosis (n = 11). Results: The results were satisfying with acceptable aesthetic and functional outcomes. Complications included haematoma underneath the BTM leading to BTM removal and re-application (n = 1), BTM infection (n = 1) and split-thickness skin graft failure on top of BTM requiring re-grafting (n = 2). Conclusions: BTM can be a good alternative to large skin grafts, locoregional flaps or even free flaps. The big advantages over other dermal substitutes or skin grafts are that BTM is less prone to infection and offers excellent scarring by preserving the normal skin architecture. Specifically in children, BTM might not require grafting, resulting in spontaneous healing with good scarring. In critically ill patients, BTM reduces the operation time and there is no donor site morbidity. BTM should be considered in the reconstructive ladder when discussing defect coverage options in children and young people. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Background/Objectives: This systematic review analyzed the epidemiologic and macro/microscopic features of manifestations of hypersensitivity reactions with oral and extra-oral involvement in orthodontic patients with fixed (FAs) or removable (RAs) appliances or clear aligners (CAs), and evaluated them based on patient and treatment characteristics to provide clinical recommendations. Methods: The study protocol followed the PRISMA guidelines and was registered on PROSPERO (CRD42024517942). Results: Thirty-one studies were qualitatively assessed and synthetized, involving 858 subjects (114 males and 714 females, 9–49 years old), of whom there were 86 with a history of allergy, and 743 wearing recorded appliances (FAs = 656, FAs and RAs = 81, intra- and extra-oral RAs = 3, CAs = 3), with a mean treatment duration of 21.5 months (6 weeks–40 months). Among 75 reports, 29 (38.67%), describing burning, gingival hyperplasia, erythema, and vesicles, had oral involvement, while 46 (61.33%) had skin, eye, and systemic involvement, with erythema, papules, conjunctival hyperemia, and vertigo. Positive allergy tests concomitant with the manifestations identified nickel 451 times, cobalt 6 times, titanium 5 times, and chromium 4 times. Management included antihistamines or corticosteroids and removing the offending materials, with treatment discontinuation/appliance substitution. Conclusions: Pre-treatment evaluations, including patient histories and allergy testing, are essential to identify potential allergens and select hypoallergenic materials like titanium or ceramic brackets; regular monitoring and early intervention during treatment are crucial to prevent severe outcomes. Full article

Background and Objectives: Previous studies have shown that a major part of adverse drug reactions (ADRs) are preventable, and they contribute to increased morbidity, mortality, and costs. To our knowledge, no study investigating preventable ADRs has been carried out in Lithuania. Therefore, the aim of this study was to characterize ADRs in the intensive care unit (ICU) of a secondary care Lithuanian hospital as well as to identify drug classes and organ systems most commonly implicated in preventable and nonpreventable ADRs. Materials and Methods: This observational prospective study was conducted in an 18-bed ICU of Kaunas Hospital of the Lithuanian University of Health Sciences from 1 September 2021 to 31 August 2023. All ADRs were assessed for causality, severity, and preventability. The Anatomical Therapeutic and Chemical (ATC) system was used to classify drug classes implicated in ADRs. The organ systems affected were analyzed using the Medical Dictionary for Regulatory Activities (MedDRA). Results: A total of 154 patients with a median age of 78.8 years (range, 18–97) were enrolled into this study. There were 255 ADRs identified; preventable ADRs accounted for 87.5%. Among the preventable ADRs, the top three therapeutic subgroups were antithrombotic agents (26.5%), anti-inflammatory and antirheumatic products (22.0%), and blood substitutes and perfusion solutions (20.2%). Meanwhile, among nonpreventable ADRs, antibacterials for systemic use (62.5%) and antithrombotic agents (46.9%) were the two most common therapeutic subgroups. The gastrointestinal as well as the skin and subcutaneous tissues organ systems were more likely to be affected by nonpreventable ADRs (56.3% vs. 17.5%, p ˂ 0.05 and 12.5% vs. 0.4%, p ˂ 0.05, respectively), while the renal and urinary organ systems were more likely to be affected by preventable ADRs (38.1% vs. 6.3%, p ˂ 0.05). Conclusions: Our study showed a very high incidence of preventable ADRs (87.5%). Drugs affecting blood and blood-forming organs were most frequently implicated in these ADRs. This area deserves special attention and strategies need to be implemented to reduce the incidence of preventable ADRs and their impact on the healthcare system. Moreover, it emphasizes the need for future studies at a national level as, to our knowledge, this is the first study addressing the issues of avoidable harm at the ICU of one Lithuanian hospital. Full article

Soft tissue reconstruction in patients with upper extremity necrotizing soft tissue infections (NSTIs) can be challenging; these defects can be large with exposed critical structures. Following appropriate source control and debridement, soft tissue reconstruction is based on size, exposed structures, medical co-morbidities and the physiologic status of the patient. There are multiple options for soft tissue coverage from local wound care to free tissue transfer. Dermal substitutes can help prepare a healthy wound bed that can later accept a skin graft. Local rotational flaps, distant pedicled flaps and free flaps are also options depending on the patient and the defect. Patients can have good functional outcomes after soft tissue reconstruction after upper extremity NSTI. Full article

Background: Burns in children represent a significant public health issue, as there is no single targeted dressing for the treatment of burn wounds in children. The alloplastic epidermal skin substitute is the dressing of choice for treating burns in children in our burn center. However, it sometimes occurs that the dressing separates from the wound too early, before the process of full re-epithelialization. The inflammatory phase of wound healing seems to be crucial for maintaining the adhesion of the dressing, and thus, changes in parameters such as leukocyte levels and protein changes are of clinical significance. The aim of our study is to find laboratory factors that could contribute to premature dressing separation. Methods: The documentation of 182 children treated for acute burns at a major Polish burn center in the years 2009–2023 was analyzed. A demographic analysis was performed to collect information. The group was split into the following two categories based on the condition of the dressing: “attached to the wound” and “detached from the wound”. Laboratory tests were collected on admission and with control tests 3–5 days after injury. Results: The results indicate that only a few of the parameters studied showed a statistically significant difference between the groups of patients in whom the dressing did or did not attach. The most pronounced relationship was found for the pre-treatment leukocyte level (leuk1). Statistical significance was also demonstrated for hemoglobin levels and changes in protein (protein_diff) and also glucose levels (glucose_diff). Conclusions: Our study shows that there are blood parameters (leukocyte, protein, and glucose levels) that influence the adhesion of the dressing. Unfortunately, there are no other studies on this topic in the literature, so it seems very important to expand research in this direction. Full article

The objectives of this study were to design, synthesize, and evaluate the antibacterial activity of a series of novel aminoguanidine-tetralone derivatives. Thirty-four new compounds were effectively synthesized through nucleophilic substitution reaction and guanidinylation reaction. Chemical structures of all the desired compounds were identified by NMR and HR-MS spectroscopy. Most of the synthesized compounds showed significant antibacterial activity against ESKAPE pathogens and clinically resistant Staphylococcus aureus (S. aureus) isolates. S. aureus is an important pathogen that has the capacity to cause a variety of diseases, including skin infections, pneumonia, and sepsis. The most active compound, 2D, showed rapid bactericidal activity against S. aureus ATCC 29213 and MRSA-2 with MIC/MBC values of 0.5/4 µg/mL and 1/4 µg/mL, respectively. The hemolytic activity and cytotoxicity of 2D was low, with HC₅₀ and IC_{50(HEK 293-T)} values of 50.65 µg/mL and 13.09 µg/mL, respectively. Compound 2D induced the depolarization of the bacterial membrane and disrupted bacterial membrane integrity, ultimately leading to death. Molecular docking revealed that dihydrofolate reductase (DHFR) may be a potential target for 2D. In the mouse skin abscess model caused by MRSA-2, 2D reduced the abscess volume, decreased bacterial load, and alleviated tissue pathological damage at doses of 5 and 10 mg/kg. Therefore, compound 2D may be a promising drug candidate for antibacterial purposes against S. aureus. Full article

Background/Objectives: The amniotic membrane, which is widely available and inexpensive, has received recent attention for its potential applications in wound healing. This is the first study to use a large database to examine the efficacy of amniotic membrane grafting compared to other skin substitutes. Methods: The TriNetX electronic health database was queried in October 2024 for patients with burns or chronic skin ulcers. Patients were stratified by treatment with amniotic membrane grafts or another skin substitute. These patients were then 1:1 propensity score-matched based on age, demographics, and comorbidities. Group differences were assessed with risk ratios and p-values. Results: A total of 557 patients remained in each group after propensity score matching. Patients who were treated with amniotic membrane grafts had significantly decreased hypertrophic scarring (1.7% vs. 6.2%, p < 0.0001), local skin infections (17.4% vs. 29.9%, p < 0.0001), and acute postoperative pain (3.7% vs. 7.8%, p = 0.003). Additionally, subsequent split-thickness skin grafting was utilized significantly less after amniotic membrane grafts. When compared to skin substitutes for large wounds (>100 cm²), the advantages of amniotic membrane were even more pronounced. Conclusions: This multi-institutional study supports amniotic membranes as a viable alternative to conventional bioengineered skin substitutes. Further research should evaluate amniotic membranes in wound beds of different sizes to better characterize their use in preparation for or as an alternative to skin grafting itself. Full article

Autologous skin substitutes represent a promising advancement in the treatment of burn injuries, offering personalized solutions for patients with extensive skin loss. This white paper synthesizes the current knowledge on laboratory-generated autologous skin substitutes in Europe, incorporating expert opinions and legal considerations. The white paper examines the scientific principles underlying autologous skin substitute development, including cell sourcing, bioengineering techniques, and clinical applications. The regulatory framework governing the production and use of these advanced therapies in Europe is also examined, highlighting challenges in standardization, safety, and approval pathways. The text features expert insights that offer a real-world perspective on the clinical viability and translational hurdles of autologous skin substitutes. The findings highlight the potential of autologous skin substitutes to improve burn treatment outcomes while emphasizing the need for harmonized regulations to facilitate clinical implementation. Despite technological advancements, significant challenges persist, including production costs, scalability, and long-term efficacy. Another focus of this white paper are the legal changes, which have significantly impacted the production and availability of these technologies. The review concludes that while autologous skin substitutes hold great promise, further research, regulatory refinement, and interdisciplinary collaboration are essential to optimize their integration into clinical practice. Full article

Considered one of the most severe types of trauma with a high impact upon patient survival, burns are the leading cause of disability-adjusted life-years (DALYs), and are responsible for high morbidity, prolonged hospitalization, disfigurement and social stigma. Of particular interest are injuries that affect the functional areas: face, neck, hand and fingers, joints, feet and soles and perineum. Burns to these regions highly influence the day-to-day activities of patients due to the formation of vicious scars and contractures, which may affect both quality of life and functional capacity. One of the primary challenges in the management of burn patients is the effective coverage of tissue defects resulting from such injuries. Cases that have a large area of burned surface also have a limited amount of total available skin. As such, the importance of skin substitutes increases, particularly in the treatment of these areas. Skin substitutes are widely utilized in plastic surgery due to their ability to promote wound healing by providing an extracellular matrix. Consequently, ongoing research has focused on developing skin substitutes that can serve as alternatives to autografts, addressing the challenges associated with large-scale tissue loss. This article aims to present and compare the most used skin substitutes, highlighting their respective advantages and limitations. This topic continues to be a subject of significant debate, as an ideal substitute has yet to be created. The cost–efficiency ratio is a practical consideration that must be tailored to each specific medical system. The available data in the literature usually present general guidelines, not rules, and as such, they need to be adapted to each patient’s necessities. Full article

Metastatic melanoma is an aggressive skin cancer with a five-year survival rate of only 35%. Despite recent advances in immunotherapy, there is still an urgent need for the development of innovative therapeutic approaches to improve clinical outcomes of patients with metastatic melanoma. Prior research from our laboratory revealed that loss of the I-branching enzyme β1,6 N-acetylglucosaminyltransferase 2 (GCNT2), with consequent substitution of melanoma surface I-branched poly-N-acetyllactosamines (poly-LacNAcs) with i-linear poly-LacNAcs, is implicated in driving melanoma metastasis. In the current study, we explored the role of galectin-3 (Gal-3), a lectin that avidly binds surface poly-LacNAcs, in dictating melanoma aggressive behavior. Our results show that Gal-3 favors binding to i-linear poly-LacNAcs, while enforced GCNT2/I-branching disrupts this interaction, thereby suppressing Gal-3-dependent malignant characteristics, including extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway activation, BCL2 expression, cell proliferation, and migration. This report establishes the crucial role of extracellular Gal-3 interactions with i-linear glycans in promoting melanoma cell aggressiveness, placing GCNT2 as a tumor suppressor protein and suggesting both extracellular Gal-3 and i-linear glycans as potential therapeutic targets for metastatic melanoma. Full article

Background and Objectives: Traditionally, full-thickness skin defects (FTSDs) are covered with split-thickness skin grafts (STSGs). This usually provides an epidermal coverage but entails a high risk of hypertrophic scarring mainly due to the absence of the dermal layer. The Novosorb^® Biodegradable Temporising Matrix (BTM) is a novel synthetic dermal substitute that has been used for the reconstruction of various complex and/or large defects in our center. The aim of this article is to evaluate the clinical performance of the BTM as a synthetic dermal substitute for complex FTSD reconstruction in a European context. Materials and methods: This case series focused on the treatment of complex FTSDs with the BTM. After wound debridement, the BTM was applied according to a defined protocol. Once adequate vascularization was observed, the sealing membrane was removed and the neo-dermis was covered with STSGs. Patient demographics, comorbidities, wound defect localization and etiology, wound bed preparations, time of BTM application and removal, time to complete wound healing after STSG, complications, and HTS formation were recorded. Results: The BTM was used to treat FTSDs in six patients with complex wounds from degloving (3), burns (1), ulcerations (1), and necrotizing fasciitis (1). Successful integration occurred in five cases (83%), with one partial integration. The BTM remained in situ for an average of 20.7 days before delamination and STSG coverage. No major complications occurred, though one case had hypergranulation with secondary STSG infection. Two patients were lost to follow-up, while the remaining four had excellent aesthetic and functional outcomes with good-quality scars. Conclusions: Within the limits of this small and heterogeneous case series, the BTM appears to be a promising option for the reconstruction of complex FTSDs of varying etiologies. Its successful integration in most cases and limited complication rate support its clinical potential. However, given this study’s retrospective design and limited sample size, further prospective studies are required to validate these findings and assess long-term outcomes. Full article

Liver fluke infections, especially those induced by Opisthorchis viverrini, pose considerable health and economic difficulties in aquaculture, particularly in Southeast Asia. Traditional approaches for parasite elimination, including chemical treatments and freezing, exhibit constraints regarding efficacy, environmental sustainability, and practicality. This research investigates an improved dielectric heating system utilizing a 2.45 GHz horn antenna for the selective thermal targeting of parasite-associated regions in Cirrhinus microlepis (small-scale mud carp). The dielectric characteristics of fish tissues, encompassing scales, skin, and muscle, were analyzed utilizing an open-ended coaxial probe technique. Simulation and experimental evaluations were performed to improve energy absorption, heating uniformity, and a particular absorption rate to enable precise thermal localization while preserving the integrity of fish tissue. The findings demonstrate that dielectric heating can specifically elevate the temperature of fish scales, where parasites predominantly inhabit, to levels beyond 70 degrees Celsius, while reducing thermal impact on the underlying muscle tissue. The application of a salt coating on fish scales markedly increased their dielectric loss, exceeding that of muscle tissue, thus enhancing selective heating efficiency and supporting targeted thermal treatment. The ideal distance from the antenna to the sample was established as ranging from 6 to 9 cm, ensuring a balance between energy efficiency and homogeneous heating. This work illustrates the efficacy of dielectric heating as a novel and non-chemical approach for thermal management of parasite-prone tissues in aquaculture, providing a sustainable and viable substitute for traditional treatments. Full article

The m.13513G>A (p.Asp393Asn) substitution in the MT-ND5 (Mitochondrially Encoded NADH/Ubiquinone Oxidoreductase Core Subunit 5) gene is a common pathogenic variant associated with primary mitochondrial disorders. It frequently causes Leigh syndrome and mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). In this study, we present clinical data, heteroplasmy levels in various tissues (blood, urine, and skin fibroblasts), and bioenergetic characteristics from a cohort of 20 unrelated patients carrying the m.13513G>A mutation, classified according to the following phenotypes: Leigh syndrome (n = 12), MELAS (n = 2), and Leber’s hereditary optic neuropathy (LHON, n = 6). We observed a significant correlation between high respiratory ratios and heteroplasmy levels in fibroblast cell lines of the patients. Furthermore, fibroblast cell lines with heteroplasmy levels exceeding 55% exhibited markedly reduced mitochondrial membrane potential. These findings contribute to a better understanding of the clinical and bioenergetic profiles of patients with m.13513G>A-variant-related phenotypes across different heteroplasmy levels, based on data from a single genetic center. Our data suggest that even a slight shift in heteroplasmy can improve cellular function and, consequently, the patients’ phenotype, providing a solid foundation for the development of future gene therapies for mtDNA diseases. Full article