The Drosophila tumor necrosis factor receptor, Wengen, couples energy expenditure with gut immunity.

It is well established that tumor necrosis factor (TNF) plays an instrumental role in orchestrating the metabolic disorders associated with late stages of cancers. However, it is not clear whether TNF/TNF receptor (TNFR) signaling controls energy homeostasis in healthy individuals. Here, we show that the highly conserved Drosophila TNFR, Wengen (Wgn), is required in the enterocytes (ECs) of the adult gut to restrict lipid catabolism, suppress immune activity, and maintain tissue homeostasis. Wgn limits autophagy-dependent lipolysis by restricting cytoplasmic levels of the TNFR effector, TNFR-associated factor 3 (dTRAF3), while it suppresses immune processes through inhibition of the dTAK1/TAK1-Relish/NF-κB pathway in a dTRAF2-dependent manner. Knocking down dTRAF3 or overexpressing dTRAF2 is sufficient to suppress infection-induced lipid depletion and immune activation, respectively, showing that Wgn/TNFR functions as an intersection between metabolism and immunity allowing pathogen-induced metabolic reprogramming to fuel the energetically costly task of combatting an infection.

Topical vanadate improves tensile strength and alters collagen organisation of excisional wounds in a mouse model.

Wound dehiscence, oftentimes a result of the poor tensile strength of early healing wounds, is a significant threat to the post-operative patient, potentially causing life-threatening complications. Vanadate, a protein tyrosine phosphatase inhibitor, has been shown to alter the organisation of deposited collagen in healing wounds and significantly improve the tensile strength of incisional wounds in rats. In this study, we sought to explore the effects of locally administered vanadate on tensile strength and collagen organisation in both the early and remodelling phases of excisional wound healing in a murine model. Wild-type mice underwent stented excisional wounding on their dorsal skin and were divided equally into three treatment conditions: vanadate injection, saline injection control and an untreated control. Tensile strength testing, in vivo suction Cutometer analysis, gross wound measurements and histologic analysis were performed during healing, immediately upon wound closure, and after 4 weeks of remodelling. We found that vanadate treatment significantly increased the tensile strength of wounds and their stiffness relative to control wounds, both immediately upon healing and into the remodelling phase. Histologic analysis revealed that these biomechanical changes were likely the result of increased collagen deposition and an altered collagen organisation composed of thicker and distinctly organised collagen bundles. Given the risk that dehiscence poses to all operative patients, vanadate presents an interesting therapeutic avenue to improve the strength of post-operative wounds and unstable chronic wounds to reduce the risk of dehiscence.

Evaluating Quality of Life After Facial Reanimation Using the Facial Clinimetric Evaluation Scale in a Series of Pediatric Patients.

BACKGROUND: Facial palsy can have significant functional and psychological impact. Dynamic facial reanimation methods have provided means of restoration of smile. There remains a dearth of quality of life data in children. The authors aim to assess patient reported outcomes in this underreported population. METHODS: A retrospective review was performed of pediatric patients with facial palsy who had dynamic facial reanimation from 2009 to 2017 at a single institution. Patients were sent a digital Facial Clinimetric Evaluation (FaCE) questionnaire, a validated tool to assess patient quality of life. FaCE statements are grouped into 6 categories: facial movement, facial comfort, oral function, eye comfort, lacrimal control, and social control. RESULTS: Twenty patients met inclusion criteria. Fourteen successfully completed the survey. With normal function being 100, our cohort scored: facial movement 38.7 ±â€Š14.3; facial comfort 67.3 ±â€Š23, oral function 75 ±â€Š22.7, eye comfort 68.75 ±â€Š18.2, lacrimal control 53.6 ±â€Š32.5, social function 64.3 ±â€Š25.6. The overall FaCE score was 61.07 ±â€Š10.85. The facial movement subscores were lower for brow raise 16.1 ±â€Š33.4 relative to smiling 53.6 ±â€Š29.2 and lip pucker, 46.4 ±â€Š23.7. No correlation was found between facial movement scores and total scores (R2 < 0.01). There was a strong negative correlation between total scores and time since procedure (Spearman's rho R =  -0.45). CONCLUSION: Our pediatric facial reanimation cohort demonstrated excellent social function, in contrast to a relatively lower facial movement score. The low facial movement score was mediated by low score for brow raise and was not correlated to overall FaCE score. Interestingly, overall FaCE score tended to decrease with time from procedure.

The limited incision harvest of the rectus femoris flap for complex groin wound management.

BACKGROUND: Muscle flaps can be effective in the protocol of complex groin wound management, yet donor-site morbidity remains a continued concern. The purpose of this study was to present a minimally invasive approach to the harvest of the rectus femoris flap (RFF) for groin wound vascularized tissue coverage. PATIENTS AND METHODS: A retrospective study examined all patients undergoing RFF coverage and reconstruction of a complex groin wound between July 1, 2010, and December 31, 2011. During the study period, the senior author (S.K.K.) performed all RFF harvests through a minimally invasive approach, whereas all other surgeons performed the RFF harvest through a standard approach. Patients who underwent a minimally invasive RFF approach were compared with those who underwent the standard incision. RESULTS: Forty-three patients underwent RFF coverage procedures, 11 of which were carried out using the minimally invasive technique. The patients in the minimally invasive cohort were older (P = 0.03) but had similar rates of medical comorbidities. Minimally invasive RFF harvests were more commonly performed in the planned, salvage setting (P = 0.03). No difference was found in the vascular surgery procedure type (P = 0.13), presence of exposed prosthetic graft material (0.2), or rate of culture-positive wound (P = 0.67). Importantly, no differences in operative time (184.4 [45.5] minutes vs 169.3 [31.7] minutes, P = 0.45) or postoperative complications were observed, with no graft losses or major limb-related morbidity in either group. CONCLUSIONS: The RFF continues to be a workhorse flap for complex groin wounds, most often in the salvage setting. This study demonstrates that a minimally invasive approach can be used for flap harvest with equivalent results to that of the standard longitudinal incision.

Topical vanadate optimizes collagen organization within granulation tissue.

Systemic ingestion of vanadate, a nonspecific inhibitor of tyrosine phosphatases, doubles wound breaking strength, enhances the packing of collagen fibers, and prevents the appearance of myofibroblasts in granulation tissue. Will the local application of vanadate mimic the systemic effects? Pairs of polyvinyl alcohol sponges, each with a central reservoir and attached injection port, were subcutaneously implanted in rats. Daily, one implant received 0.2 ml of saline and the other received 0.2 ml of 0.03 mM vanadate in saline. On day 7, harvested sponges had equivalent wet weights. The vanadate-treated sponges had fibroblasts separated by connective tissue, with a more intense birefringence of the collagen fibers. Transmission electron microscopy showed collagen more uniformly packed in the vanadate treated sponges where collagen fibers were equally spaced and had equal diameters. By immunohistology, myofibroblasts, defined by the expression of alpha-smooth muscle actin within stress fibers, were absent in vanadate-treated granulation tissue. The expression of alpha-smooth muscle actin was restricted to smooth muscle cells of blood vessels. Controls had densely packed alpha-smooth muscle actin staining myofibroblasts, weak birefringence, and randomly spaced collagen fibers with irregular diameters. We conclude that the local application of vanadate prevents the appearance of myofibroblasts and optimizes the organization of collagen fibers in developing granulation tissue.