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The percentage of skin graft take following the resurfacing of burn injuries is routinely calculated in a subjective fashion, in order to make management decisions. Given the gravity of decisions made based on this clinical assessment of graft check, it is notable that limited research has been carried out on this subject. No standardised subjective assessment tools exist to measure surface area of graft take in a manner similar to that of Wallace's Rule of Nines or Lund and Browder. This study set out to examine the accuracy of visual assessments of graft take within the multidisciplinary team regularly making assessments of newly grafted burn wounds. A total of 15 digitally drawn images were used to assess 36 staff members' estimations of percentage of surface area. The results showed a wide variation in estimation in all staff types, including senior burns surgeons, who were found to underestimate surface area by as much as 30%. The British Burns Association has removed 'healing time' as an outcome measurement from its guidance, as it recognises how hard it is to make a standardised assessment of wound healing. This study demonstrates the difficulty in subjectively assessing surface area and makes some suggestions for further research and clinical applications of technology to aid assessment.

Hyaluronan is a vital constituent in effective skin wound healing. This polysaccharide is ubiquitous throughout the human body and has functional significance for tissue repair and remodelling. The importance of hyaluronan in the proliferative phase of healing is diverse, impacting on cell migration, proliferation, modification of the inflammatory response and on angiogenesis. As such, it holds therapeutic potential for a variety of clinical applications that range from facilitating effective wound healing to burns management and scarring. This overview of the multifaceted roles of hyaluronan considers its current applications to clinical practice in plastic surgery as well as the latest advances in research.

The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.

A 10-year-old boy struck a car bonnet following which his left shoulder got pinned under the wheel. No life-threatening injuries were identified. However, the patient sustained extensive abrasions to the back and the left shoulder, a closed deformity of the left clavicle and a swollen, but stable right knee. The patient was neurovascularly intact globally and all joints had a full range of motion. Plain radiographs suggested a possible greenstick fracture of the left clavicle, but also free gas within the left glenohumeral joint. Concern was raised of an unidentified open injury to the joint. CT was supportive of the finding of gas within the left glenohumeral joint, but ruled out the possible greenstick fracture as a spurious finding. There were no other injuries. The gas was within the left glenohumeral joint and was consistent with vacuum phenomenon. The injury was treated expectantly and the child made a full recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Transition to interprofessional team-based care is a quickly progressing healthcare model and requires changes in medical training approaches. The Department of Veteran Affairs (VA) has taken a lead role in creating such training experiences, one of which is the establishment of multiple Centers of Excellence in Primary Care Education (CoEPCE). These sites are tasked with developing teaching innovations to better facilitate interprofessional team-based care. The patient-aligned care team interprofessional care update (PACT-ICU) is an interprofessional workplace learning activity with the goals of simultaneously addressing educational and patient care needs. Participants of the PACT-ICU included trainees and faculty of a variety of medical disciplines (e.g., internal medicine, psychology, and pharmacy) involved in a training primary care clinic. Two medically complex patients were presented at each PACT-ICU conference with the purpose of creating a plan of care that maintained an interprofessional team-based approach. Following implementation of the PACT-ICU conference intervention, two primary outcomes were assessed. First, self-assessment of PACT-ICU attendee learner outcomes was measured using a brief questionnaire surveying knowledge gain as it related to increase in knowledge of other professions' capabilities, roles, and responsibilities. Secondly, trainee provider behavior change was evaluated by measuring number of "within PACT" consults before and after participating in PACT-ICU. There was a significant positive change in self-assessed knowledge along with an indication of trainee behavioral change, as measured by electronic medical record consult patterns. This study demonstrates that interprofessional case conferences involving trainees and staff from multiple professions can increase awareness of other professions roles in patient care as well as facilitate interprofessional collaboration.

Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal ( ortho ) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of ortho IL-2Rβ into T cells enabled the selective cellular targeting of ortho IL-2 to engineered CD4 + and CD8 + T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. Ortho IL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here, we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followed by amino acid sequence optimization at the newly formed strand-strand, strand-helix, and helix-helix interfaces. Crystal structures of two such designs closely match the computational design models. Searches for similar structures in the SCOP protein domain database yield only weak matches with different beta sheet connectivities. A similar beta sheet fusion mechanism may have contributed to the emergence of complex beta sheets during natural protein evolution.

Unlabelled: Bites and scratches are common injuries, frequently sustained from humans, dogs and cats. Exotic pet-related harm however is an important and increasingly emerging class of injury. Whilst the principles of prompt and thorough medical assessment, antibiotics and potential surgical washout and debridement apply, exotic pet wounds require further consideration. Standard antibiotic prophylaxis with amoxicillin/clavulanic acid (also known as co-amoxiclav) is not sufficient for the pathogens transmitted by parrot bites. We illustrate the importance of adequate consideration of microbiological pathogens with a case report of an open finger fracture resulting from a parrot bite. We intend this to be a valuable resource for healthcare professionals in their effective management of such injuries., Level of Evidence: V.

Pilomatrixomas are benign cutaneous tumors derived from hair matrix cells of unclear etiology. Pilomatrixomas commonly demonstrate somatic mutations in CTNNB1, a gene coding β-catenin, a protein involved with hair follicle development. Multiple familial pilomatrixomas rarely occur and are most often associated with autosomal dominant conditions such as myotonic dystrophy and familial adenomatous polyposis (FAP). Nine families with multiple familial pilomatrixomas and no demonstrable underlying association have been reported in the literature. We present a tenth family in which five members spanning three generations grew multiple pilomatrixomas in the absence of any previously reported associations. No evidence of myotonic dystrophy, FAP, or other known associations was found. Extreme tiredness, behavioral problems, and sensory disturbances were common features across three generations but bore no temporal relation to the pilomatrixomas. The existence of a germline mutation in CTNNB1 to explain these symptoms has yet to be shown. Pilomatrixomas are potentially cutaneous markers of significant underlying pathologies. Patients presenting with multiple or familial pilomatrixomas should be thoroughly assessed for other pathologies and offered genetic screening to ensure that important diagnoses are not overlooked., (© 2014 Wiley Periodicals, Inc.)

Nasal reconstruction after severe panfacial burns can be challenging to correct because of scarring, loss of suitable donor sites, and variably limited blood supply of local flaps. We describe 2 cases of subtotal nasal reconstruction in which we overcame these difficulties. Both cases had alar subunit loss, which had left significant functional and esthetic deformities. However, both cases were managed very differently because of availability of donor sites.The first patient had 70% total body surface area burns with bilateral alar subunit loss: nasal reconstruction required a meticulous multistaged forehead flap. The second patient required nasal reconstruction using a turn-down flap to maximize take of a composite graft from previously burned ear donor sites.A number of surgical techniques have been described to manage subtotal burns nasal reconstruction, foremost of which are the nasolabial and paramedian forehead flaps. Cartilage grafts from the septum and the conchal bowl can be integrated into these flaps. Composite grafts can be unpredictable and are often used with caution.Such cases demonstrate that large composite grafts can be an extremely robust method of reconstruction even in a subset of patients with extensively scarred recipient and donor sites. In our second case, composite grafting avoided multistaged procedures such as the forehead flap and can be considered as a first-line procedure in large alar subunit loss.

Background: An inferior dermal flap with implant is a useful option for women hoping for immediate breast reconstruction. This one-stage procedure uses autologous tissue as an inferolateral local sling, avoiding the costs and potential morbidity of prosthetic mesh and reducing valuable operating time. Patient comorbidity or choice may restrict autologous reconstruction options available. Many patients will still require a second procedure for subsequent nipple reconstruction and further appointments and costs for tattooing., Method: A prospective database was kept of a single surgeon's experience with 16 patients (19 breasts) from 2010 to 2012. Reconstruction was performed following a Wise pattern skin incision. An inferior, deepithelialized dermal sling was sutured to the pectoralis major to form a pocket for a silicone implant or tissue expander. A free nipple graft was sited at the time of reconstruction, with biopsies taken from retroareolar tissue., Results: Patient average age was 54 years (range 36-66). Six mastectomies were for ductal carcinoma in situ, 6 for invasive carcinoma, 2 for lobular carcinoma, and 5 of 19 mastectomies were prophylactic. Average operative time was 165 min. There were no immediate complications requiring reoperation. All retroareolar biopsies were benign and no locoregional recurrences have occurred. Two nipples had partial necrosis of the lower pole but healed with conservative treatment. No patients required any subsequent procedures to their reconstructed breast., Conclusion: The inferior dermal flap with implant and free nipple graft is an excellent single-stage reconstruction option. This method offers a potentially safe, reliable, and aesthetically acceptable outcome for women with larger, ptotic breasts., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Introduction. Buried penis is a difficult condition to manage in children and adults and conveys significant physical and psychological morbidity. Surgery is often declined due to morbid obesity, forcing patients to live in disharmony for years until the desired weight reduction is achieved. No single operative technique fits all. We present our experience and surgical approach resulting in an improved algorithm unifying the treatment of adults and children. Methods. We conducted a retrospective analysis of patients treated for buried penis between 2011 and 2012. All patients underwent penile degloving and basal anchoring. Penile shaft coverage was achieved with skin grafts. Suprapubic lipectomies were performed on adult patients. Results. Nine patients were identified: four children and five obese adults. Average postoperative stay was three days for children and five for adults. Three adults were readmitted with superficial wound problems. One child had minor skin breakdown. All patients were pleased with their outcomes. Conclusion. Buried penis is a complex condition, and treatment should be offered by services able to deal with all aspects of reconstruction. Obesity in itself should not delay surgical intervention. Local and regional awareness is essential to manage expectations in these challenging patients aspiring to both aesthetic and functional outcomes.

The development of novel cancer therapies that are selective for cancer cells with limited toxicity to normal tissues is a challenge for oncology researchers. Microorganisms, such as viruses with selectivity for tumor cells or tumor micro-environments, have been investigated as potential arsenals for decades. Genetically-modified, non-pathogenic bacteria have begun to emerge as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Attenuated Salmonella, Clostridium and Bifidobacterium are capable of multiplying selectively in tumors and inhibiting their growth, representing a new approach for cancer treatment. Because of their selectivity for tumor tissues, these bacteria would also be ideal vectors for delivering therapeutic proteins to tumors. VNP20009, an attenuated strain of Salmonella typhimurium, and its derivative, TAPET-CD, which expresses an Escherichia coli cytosine deaminase (CD), are particularly promising, and are currently undergoing phase I clinical trials in cancer patients.

VNP20009, a genetically modified strain of Salmonella typhimurium with deletions in the msbB and purI loci, exhibited antitumor activities when given systemically to tumor-bearing mice. VNP20009 inhibited the growth of subcutaneously implanted B16F10 murine melanoma, and the human tumor xenografts Lox, DLD-1, A549, WiDr, HTB177, and MDA-MB-231. A single intravenous injection of VNP20009, at doses ranging from 1 x 10(4) to 3 x 10(6) cfu/mouse, produced tumor growth inhibitions of 57-95%. Tumor volume doubling time, another indicator for tumor growth inhibition, also significantly increased in mice treated with VNP20009. Using mice with immune system deficiencies, we also demonstrated that the antitumor effects of VNP20009 did not depend on the presence of T and B cells. In addition, VNP20009, given intravenously, inhibited the growth of lung metastases in mice. Only live bacteria showed the antitumor effect.

Attenuated strains of Salmonella typhimurium, VNP20009 and YS7212, when injected systemically to tumor-bearing mice, accumulated preferentially in tumors at levels at least 200-fold and, more commonly, 1000-fold greater than in other normal tissues. This selectivity occurred in subcutaneously implanted murine tumors, including B16F10 melanoma, M27 lung carcinoma, and colon 38 carcinoma. The preferential accumulation was also manifested in animals bearing human tumor xenografts, including Lox, C8186, DLD1, SW620, HCT116, HTB177, DU145, MDA-MB-231, and Caki. Four to five days after a single IV injection of 1 x 10(6) colony-forming unit (cfu)/mouse, we routinely detected VNP20009 proliferation and accumulation at levels ranging from 1 x 10(8) to 2 x 10(9) cfu/g tumor. The amount of VNP20009 accumulated in the liver ranged from 3 x 10(4) to 2 x 10(6) cfu/g. The distribution of Salmonella in tumors was homogenous; YS7212 could be detected from the periphery to the interior portion of the tumors. Using mice with various immunodeficiencies, we also discovered the same preferential accumulation of Salmonella in tumors implanted in these mice. The use of Salmonella as a protein delivery vector was shown by IV administration of the bacteria expressing either green fluorescent protein (GFP) or cytosine deaminase (CD) into tumor-bearing mice. GFP and CD were detected in tumors, but not in livers, taken from mice inoculated with Salmonella carrying these genes. Bacteria accumulation and CD expression persisted in the tumors for up to 14 days after a single bolus IV administration of bacteria to tumor-bearing mice.

The in vivo induction of the differentiation of murine WEHI-3B D+ myelomonocytic leukemia cells was measured by flow cytometry, simultaneously staining leukemia cells for the marker exogenous beta-galactosidase and for differentiation by the antigen Mac-1 (CD11b/CD18). The WEHI-3B D+ leukemia cells were transfected with the E. coli lac-Z gene by electroporation and subclones that constitutively expressed high levels of the lac-Z gene product beta-galactosidase were established. Flow cytometric analyses of cells in the peritoneal cavities of mice bearing leukemia cells showed that cells continued to express beta-galactosidase for at least 14 days, and they were distinguishable from host-derived cells in vivo by their expression of the transfected gene. Simultaneous determination of the beta-galactosidase activity and Mac-1 content of cells in the peritoneal cavities of mice revealed that administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the mice enhanced the expression of Mac-1 antigen by beta-galactosidase-positive cells. The results demonstrate that G-CSF may have clinical potential as a therapeutic differentiating agent, and that flow cytometric analysis provides a useful in vivo system to evaluate the therapeutic potential of agents capable of inducing terminal differentiation.

We have developed a colorimetric assay for the examination of inhibitors of epidermal growth factor (EGF) receptor-associated tyrosine kinase in intact cells. EGF receptor from cells treated with inhibitors is captured by an anti-EGF receptor antibody and the phosphotyrosine content is measured by an anti-phosphotyrosine antibody. The quantitative assay does not use radioactive substances and is configured for a high-throughput format. Since it is performed in intact cells, substances lower the phosphotyrosine content on the receptor by different mechanisms will be identified. One distinct feature of the assay is that it uses the natural substrate inside the cell as compared to others using artificial substrates in an unphysiological environment. This assay is easy to perform, is reproducible, and is compatible with many organic solvents and tissue culture media. Thus, it is useful for the discovery of EGF receptor kinase inhibitors from natural products or synthetic compounds and is particularly suitable for large-scale screening.

A rapid and sensitive nonradioactive ligand binding assay for identifying the agonists and antagonists of epidermal growth factor receptor is described. The assay is easy to perform, has a within-assay error of less than 15%, and does not use radioactive substances. Nonspecific binding is less than 10% and the assay is sensitive enough to detect epidermal growth factor (EGF) antagonists at as little as 10 nM, if the antagonist has the same affinity as EGF. The assay is carried out in 96-well plates and is particularly suitable for large-scale screening. This report includes description of the methods that we used to assess the validity of the assay system, and the results of that assessment.

The replication of human epidermoid carcinoma A431 cells is inhibited by epidermal growth factor (EGF), with 5 ng/ml of EGF causing 50% inhibition of cellular proliferation. EGF resistant clones isolated from A431 cells were able to replicate in the presence of 100 ng/ml of EGF. That this insensitivity to EGF was probably due to a decrease in the expression of EGF receptors (EGFR) on the cell surface was shown using an EGFR cDNA probe to detect a 68% to 85% decrease relative to parental cells in the amount of EGFR mRNA in the EGF resistant clones. A corresponding decrease in surface EGFR levels was also detected in EGF resistant clones as measured by 125I-EGF binding. Eighteen percent of A431 cells cultured in serum-free medium for 6 days entered a pathway of terminal differentiation, as expressed by the formation of envelope-competent cells, whereas EGF resistant clones exhibited a considerably greater capacity to mature, even when cultured in serum-containing medium. The findings suggest that the concentration of EGFRs is important for the capacity of epidermal cells to undergo terminal differentiation in vitro.