Negative pressure wound therapy is useful in pediatric burn patients, a retrospective review

INTRODUCTION: Negative pressure wound therapy (NPWT) has proved to be a powerful tool in facilitating the healing of difficult wounds of a variety of etiologies. The pediatric experience with NPWT has been limited because of concerns about vascular compression and pain associated with treatment. METHOD: A retrospective review (2004-2014) was conducted at Shriners Hospital for Children-Boston to evaluate the therapeutic effect of NPWT on children with difficult wounds due to burns or soft-tissue trauma. Information was collected on patient demographics, wound size and depth, burn injury etiology, length of hospital stay, number of operating room visits, and other treatment procedures. NPWT was instituted in the operating room under general anesthesia using a commercially available system. NPWT was not initiated until all necrotic material had been removed from the wounds. A negative pressure varying between -50 and -125 mmHg was applied to the wound as continuous suction, with younger children being prescribed the lower negative pressures. NPWT dressings were changed every 5-7 days in the operating room. When wounds were clean and granulated, they were closed with split-thickness skin grafts. RESULTS: Twenty-nine children with an average age of 9.43 +/- 1.95 years (range 2 months to 18 years) were treated with NPWT. The average total wound size was 24.8 +/- 8.9% (range 0%-95%) of the body surface in patients who had suffered burns and non-burn injuries. Injury mechanisms were categorized as hot liquid (2 children), contact with hot object (4 children), electricity (7 children), flame (9 children), and other non-burn injuries such as abrasion and degloving (7 children). Over 90% of the patients required central venous or bladder catheters. Perceived benefits of the treatment included reduced numbers of dressing changes and more rapid wound granulation. There were no episodes of bleeding associated with NPWT. All patients healed their wounds, were successfully grafted, and survived. CONCLUSION: NPWT has a useful role in the pediatric burn unit in facilitating wound healing and improving quality of life. A significant correlation between the size of third-degree burn wounds and the number of negative pressure therapies suggests that NPWT may be more effective in treating complicated burn wounds. Overall, NPWT appears safe and effective when applied to well-debrided wounds, and the treatment does not seem to be associated with excessive bleeding or discomfort in children

Note Taking Exercises Improve Students’ Reading and Problem Solving Abilities

poster, CAS 352/SG, spring 201

Gut bioengineering promotes gut repair and pharmaceutical research: a review

The gastrointestinal (GI) tract has a diverse set of physiological functions, including peristalsis, immune defense, and nutrient absorptions. These functions are mediated by various intestinal cells such as epithelial cells, interstitial cells, smooth muscle cells, and neurocytes. The loss or dysfunction of specific cells directly results in GI disease, while supplementation of normal cells promotes gut healing. Gut bioengineering has been developing for this purpose to reconstruct the damaged tissues. Moreover, GI tract provides an accessible route for drug delivery, but the collateral damages induced by side effects cannot be ignored. Bioengineered intestinal tissues provide three-dimensional platforms that mimic the in vivo environment to study drug functions. Given the importance of gut bioengineering in current research, in this review, we summarize the advances in the technologies of gut bioengineering and their applications. We were able to identify several ground-breaking discoveries in our review, while more work is needed to promote the clinical translation of gut bioengineering

Bioinspired Anti-digestive Hydrogels Selected by a Simulated Gut Microfluidic Chip for Closing Gastrointestinal Fistula

Summary: The anti-digestive features given to hydrogels can prolong their action time in gut environment; however, these types of hydrogels have rarely been reported. Inspired by indigestibility of dietary fibers, we introduced an injectable covalent hydrogel through photopolymerization of glycidyl methacrylate-modified xanthan. This newly synthesized hydrogel exhibited a specific concentration-dependent porosity, swelling ratio, and stiffness. The intestinal epithelial cells-6 could grow on the surface of the stiffer hydrogel, and achieved their gut barrier functions. A simulated gut microfluidic chip was manufactured to demonstrate the hydrogel's good performance of anti-digestion compared with the current product, fibrin sealant. Furthermore, calcium ions could induce the swelling-shrinking behavior of the hydrogel, which assisted in removing the hydrogels at the proper time so as to avoid the mismatch of hydrogel degradation and tissue regeneration. Therefore, this hydrogel is expected to be an outstanding gut repair material, especially for closing gastrointestinal fistula. : Surgery; Polymers; Biomaterials; Biomedical Materials Subject Areas: Surgery, Polymers, Biomaterials, Biomedical Material

PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation

Abstract Background Paired box 1 (PAX1) is a transcription factor and essential for the development of pharyngeal pouches-derived tissues, including thymus. PAX1 mutations are identified in Severe Combined Immunodeficiency (SCID) patients with Otofaciocervical Syndrome Type 2 (OTFCS2). However, despite the critical roles of PAX1 in embryonic development and diseases, detailed insights into its molecular mode of action are critically missing. Methods The repressing roles of PAX1 and SCID associated mutants on Wnt signaling pathway were investigated by luciferase reporter assays, qRT-PCR and in situ hybridization in HEK293FT, HCT116 cells and zebrafish embryos, respectively. Co-immunoprecipitation (co-IP) and western blotting assays were carried out to identify the molecular mechanisms underlying PAX1’s role on Wnt signaling pathway. hESC based endoderm differentiation, flow cytometry, high-throughput sequencing data analysis, and qRT-PCR assays were utilized to determine the roles of PAX1 during endoderm differentiation. Results Here, we show that PAX1 represses canonical Wnt signaling pathway in vertebrate cells. Mechanically, PAX1 competes with SUMO E3 ligase PIASy to bind to TCF7L2, thus perturbing TCF7L2 SUMOylation level, further reducing its transcriptional activity and protein stability. Moreover, we reveal that PAX1 plays dual roles in hESC-derived definitive and foregut/pharyngeal endoderm cells, which give rise to the thymus epithelium, by inhibiting Wnt signaling. Importantly, our data show PAX1 mutations found in SCID patients significantly compromise the suppressing ability of PAX1 on Wnt signaling. Conclusions Our study presents a novel molecular mode of action of PAX1 in regulation of canonical Wnt signaling and endoderm differentiation, thus providing insights for the molecular basis of PAX1 associated SCID, offering better understanding of the behavior of PAX1 in embryogenesis

Palmitoylethanolamide-Incorporated Elastic Nano-Liposomes for Enhanced Transdermal Delivery and Anti-Inflammation

Palmitoylethanolamide (PEA) exhibits multiple skincare functions such as anti-nociceptive and anti-inflammatory effects. However, its topical application is limited due to its difficulty in bypassing the stratum corneum barrier, relatively low bioavailability, and low stability. Herein, elastic nano-liposomes (ENLs) with excellent deformability and elasticity were utilized as a novel drug delivery system to encapsulate PEA to overcome the abovementioned issues and enhance the biological effects on the skin. ENL was prepared with phosphatidylcholine, cholesterol, and cetyl-PG hydroxyethyl palmitamide with a molar ratio mimicking skin epidermal lipids, and PEA was loaded. The PEA-loaded ENL (PEA-ENL) demonstrated efficient transdermal delivery and enhanced skin retention, with negligible cytotoxicity toward HaCaT cells and no allergic reaction in the human skin patch test. Notably, PEA-ENL treatment increased cell migration and induced significant regulation in the expression of genes associated with anti-nociceptive, anti-inflammatory, and skin barrier repair. The mechanism of the anti-nociceptive and anti-inflammatory effects of PEA was further investigated and explained by molecular docking site analysis. This novel PEA-ENL, with efficient transdermal delivery efficiency and multiple skincare functionalities, is promising for topical application

Early Enteral Nutrition Preserves Intestinal Barrier Function through Reducing the Formation of Neutrophil Extracellular Traps (NETs) in Critically Ill Surgical Patients

Background. The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. Methods. Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. Results. The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. Conclusion. The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity