Deformation gradients imprint the direction and speed of en masse fibroblast migration for fast healing

En masse cell migration is more relevant than single cell migration in physiological processes of tissue formation, such as embryogenesis, morphogenesis and wound healing. In these situations, cells are influenced by the proximity of other cells including interactions facilitated by substrate mechanics. Here we found that when fibroblasts migrated en masse over a hydrogel, they established a well-defined deformation field by traction forces and migrated along a trajectory defined by field gradients. The mechanics of the hydrogel determined the magnitude of the gradient. For materials stiff enough to withstand deformation related to cellular traction forces, such patterns did not form. Furthermore, migration patterns functioned poorly on very soft matrices where only a minimal traction gradient could be established. The largest degree of alignment and migration velocity occurred on the gels with the largest gradients. Granulation tissue formation in punch wounds of juvenile pigs was correlated strongly with the modulus of the implanted gel in agreement with in vitro en masse cell migration studies. These findings provide basic insight into the biomechanical influences on fibroblast movement in early wounds and relevant design criteria for development of tissue-engineered constructs that aim to stimulate en masse cell recruitment for rapid wound healing

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

<p>Abstract</p> <p>Background</p> <p>Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.</p> <p>Methods</p> <p>Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.</p> <p>Results</p> <p>By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (<it>p </it>< 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.</p> <p>Conclusion</p> <p>This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.</p

Faculty members\u27 perceptions of medical genetics and its integration into nurse practitioner curricula

This study assessed faculty members\u27 perceived knowledge of medical genetics concepts and conditions, the importance of integrating this content into NP curricula and how this was being done. During a national NP conference, 40 NP faculty voluntarily completed surveys. Participants\u27 perceived knowledge of genetics varied; 35% noted low or very low knowledge, and only 5% reported high or very high knowledge. Most participants (95%) believed genetics is important, but only 10% reported having separate genetics courses in their NP programs. Approximately half of the participants reported personal involvement in genetics NP education, and 50% reported barriers to implementing it into their curricula. Most faculty indicated they did not feel comfortable teaching genetics, nor did they have formal training in the area. Advancing medical genetics into NP curricula will require ongoing faculty development and training to sustain and build genetics skills and competencies for advanced practice nurses

Knowledge, perceptions, and attitudes of advanced practice nursing students regarding medical genetics.

PURPOSE: To describe the current medical genetic knowledge and perceptions of graduate advanced practice nursing (advanced practice nurse [APN]/nurse practitioner and nurse anesthetist) students using survey data for future integration of genetic topics, principles, and healthcare issues into curriculum. DATA SOURCES: Survey data of APNs\u27 perceived knowledge of genetics and a review of the literature from past research studies of students and current articles from professional journals and organizations. Web sites were those of the National Coalition of Health Professions for Education in Genetics and National Institutes of Health, Human Genome Research Institute; professional organizations; and the authors\u27 professional, clinical, and educational experiences. CONCLUSIONS: Most APN students perceived they had minimum knowledge and prior training regarding medical genetics. There is a need to integrate genetic concepts, principles, and medical conditions into advanced practice nursing curriculum and to provide clinical experiences in genetic conditions across the life span and throughout the health and illness spectrum. APN students have positive attitudes toward integrating genetics into graduate curricula. Potential methods for program integration include readings, small group discussion, standardized patients, and role-play as measures to increase information. IMPLICATIONS FOR PRACTICE: The National Coalition for Health Profession Education in Genetics, the American Nursing Association, and the American College of Nursing Education have recommended integration of genetics knowledge and skills into routine health care to provide effective interventions for individuals and families. However, previous research and data from this study have revealed that many nurses have minimal training in genetics. Advanced practice nurses must be knowledgeable on genetic principles, topics, and the ethical, legal, and social implications related to medical genetics to increase the ability to diagnose, prevent, and treat diseases and to provide effective care for individuals and families

Topical Delivery of Immunosuppression to Prolong Xenogeneic and Allogeneic Split-Thickness Skin Graft Survival

Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)–mediated hyperacute rejection and are lost by POD 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression. In this study, we investigate topical immunosuppression as an alternative to prolong xenograft survival. Full-thickness wounds in baboons were created and covered with xenogeneic and allogeneic split-thickness skin grafts (STSGs). Animals were treated with slow-release (TyroSphere-encapsulated) topical formulations (cyclosporine-A [CSA] or Tacrolimus) applied 1) directly to the STSGs only, or 2) additionally to the wound bed before STSG and 1). Topical CSA did not improve either xenograft or allograft survival (median: treated grafts = 12.5 days, control = 14 days; P = 0.27) with similar results when topical Tacrolimus was used. Pretreatment of wound beds resulted in a significant reduction of xenograft survival compared with controls (10 vs 14 days; P = 0.0002), with comparable results observed in allografts. This observation was associated with marked reduction of inflammation on histology with Tacrolimus and not CSA. Prolongation of allograft and xenograft survival after application to full-thickness wound beds was not achieved with the current formulation of topical immunosuppressants. Modulation of inflammation within the wound bed was effective with Tacrolimus pretreatment before STSG application and may serve as a treatment strategy in related fields