32 research outputs found
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Absolute Enrichment: Gene Set Enrichment Analysis for Homeostatic Systems
The Gene Set Enrichment Analysis (GSEA) identifies sets of genes that are differentially regulated in one direction. Many homeostatic systems will include one limb that is upregulated in response to a downregulation of another limb and vice versa. Such patterns are poorly captured by the standard formulation of GSEA. We describe a technique to identify groups of genes (which sometimes can be pathways) that include both up- and down-regulated components. This approach lends insights into the feedback mechanisms that may operate, especially when integrated with protein interaction databases
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Patient Satisfaction and Surgeon Experience: A Follow-Up to the Reduction Mammaplasty Learning Curve Study
Background: While it is known that increasing surgeon experience is correlated with improved efficiency and safety in the reduction mammaplasty procedure, it is unclear whether these improvements lead to an erosion in patient satisfaction. Methods: The authors distributed the Breast-Q questionnaire to all patients who underwent bilateral reduction mammaplasty at their institution between 1995 and 2007. Univariate and multivariate analyses were performed to assess the relationship between postoperative patient satisfaction scores and surgeon experience, as well as to characterize those patients with particularly high or low satisfaction scores, in general. Results: A total of 279 (26.1%) completed surveys were analyzed. No statistically significant erosion in either Satisfaction with Breasts (SWB) or Satisfaction with Outcomes (SWO) scores were witnessed with increasing surgeon experience or efficiency. Patients older than 40 years demonstrated significantly higher SWB scores than younger patients (P = .004), while patients who suffered postoperative soft tissue necrosis demonstrated significantly lower SWB (P = .003) and SWO (P = .010) scores. Conclusions: Gains in operative efficiency with increasing surgeon experience do not appear to come at the expense of patient satisfaction in the reduction mammaplasty procedure. Younger patients and those who experience postoperative soft tissue necrosis appear to be at higher risk for reporting lower postoperative patient satisfaction scores
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Hair follicle melanocyte cells as a renewable source of melanocytes for culture and transplantation
Objective: Advances in melanocyte culture techniques have not yet led to reliable clinical methods for treating hypopigmentation disorders. We hypothesized that melanocytes harvested from plucked hair follicles may provide a renewable source of melanocytes for the treatment of hypopigmentation. Methods: Hairs with attached cells from the follicles were plucked from Yucatan pigs and implanted in a collagen-glycosaminoglycan matrix for either immediate or delayed implantation into full-thickness excisional porcine wounds. Wounds were allowed to heal and were biopsied at 2 and 4 weeks, respectively. Results: Fully healed wounds with transplanted hair follicles showed central areas of dark pigmentation corresponding to the location of implanted hair follicles. Corresponding collagen-glycosaminoglycan matrix wounds showed no central areas of pigmentation. Conclusions: Hair follicle--derived melanocytes may potentially serve as a renewable source of pigment-producing cells for treating hypopigmentation disorders
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The First 500 Registrations to the Research Registry®: Advancing Registration of Under-Registered Study Types
Introduction: The Declaration of Helsinki 2013 encourages the registration of all research studies involving human participants. However, emphasis has been placed on prospective clinical trials, and it is estimated that only 10% of observational studies are registered. In response, Research Registry®1 was launched in February 2015; a retrospectively curated registry that is free and easy to use. Research Registry® enables prospective or retrospective registration of studies, including those study types that cannot be registered on existing registries. In this study, we describe the first 500 registrations on Research Registry®. Methods: Since the launch of Research Registry® in February 2015, data of registrations have been collected, including type of studies registered, country of origin, and data curation activity. Inappropriate registrations, such as duplicates, were identified by the data curation process. These were removed from the database or modified as required. A quality score was assigned for each registration, based on Sir Austin Bradford Hill’s criteria on what research studies should convey. Changes in quality scores over time were assessed. Results: A total of 500 studies were registered on Research Registry® from February 2015 to October 2015, with a total of 1.7 million patients enrolled. The most common study types were retrospective cohort studies (37.2%), case series (14.8%), and first-in-man case reports (10.4%). Registrations were received from 57 different countries; the most submissions were received from Turkey, followed by China and the United Kingdom. Retrospective data curation identified 80 studies that were initially registered as the incorrect study type, and were subsequently correct. The Kruskal–Wallis test identified a significant improvement in quality scores for registrations from February 2015 to October 2015 (p < 0.0001). Conclusions: Since its conception in February 2015, Research Registry® has established itself as a new registry that is free, easy to use, and enables the registration of various study types, including observational studies and first-in-man case reports. Going forward, our plan is to continue developing Research Registry® in line with user feedback and usability studies. We plan to further promote Research Registry® to advance the cause of registration of research, to increase compliance with the Declaration of Helsinki 2013
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Use of autologous fat grafting for reconstruction postmastectomy and breast conserving surgery: a systematic review protocol
Introduction
There is growing interest in the potential use of autologous fat grafting (AFG) for the purposes of breast reconstruction. However, concerns have been raised regarding the technique's clinical effectiveness, safety and interference with screening mammography. The objective of this systematic review was to determine the oncological, clinical, aesthetic and functional, patient reported, process and radiological outcomes for AFG.
Methods and analysis
All original studies, including randomised controlled trials, cohorts studies, case–control studies, case series and case reports involving women undergoing breast reconstruction. All AFG techniques performed for the purposes of reconstruction in the postmastectomy or breast conserving surgery setting will be considered. Outcomes are defined within this protocol along; oncological, clinical, aesthetic and functional, patient reported, process and radiological domains. The search strategy has been devised to find papers about ‘fat grafting and breast reconstruction’ and is outlined within the body of this protocol. The full search strategy is outlined within the body of the protocol. The following electronic databases will be searched from 1 January 1986 to 6 June 2013: PubMed, MEDLINE, EMBASE, SCOPUS, CINAHL, PsycINFO, SciELO, The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effect (DARE), the Cochrane Methodology Register, Health Technology Assessment Database, the NHS Economic Evaluation Databases and Cochrane Groups, ClinicalTrials.gov, Current Controlled Trials Database, the World Health Organisation (WHO) International Clinical Trials Registry Platform, UpToDate.com, NHS Evidence and the York Centre for Reviews and Dissemination. Grey literature searches will also be conducted as detailed in our review protocol. Eligibility assessment occurred in two stages, title and abstract screening and then full text assessment. Data were extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry.
Ethics and dissemination
This systematic review will be published in a peer-reviewed journal. It will also be presented at national and international conferences in the fields of plastic, reconstructive and aesthetic surgery and at more general surgical and methodological conferences. It will be disseminated electronically and in print. Brief reports of the review findings will be disseminated directly to the appropriate audiences of surgeons and societies through email and other modes of communication. Updates of the review will be conducted to inform and guide healthcare practice and policy.
Protocol Registration
PROSPERO—National Institute of Health Research (NIHR) Prospective Register of Systematic Reviews (CRD42013005254
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The Effect of Hydrostatic Pressure on Three-Dimensional Chondroinduction of Human Adipose–Derived Stem Cells
Background: The optimal production of three-dimensional cartilage in vitro requires both inductive factors and specified culture conditions (e.g., hydrostatic pressure [HP], gas concentration, and nutrient supply) to promote cell viability and maintain phenotype. In this study, we optimized the conditions for human cartilage induction using human adipose–derived stem cells (ASCs), collagen scaffolds, and cyclic HP treatment.
Methods: Human ASCs underwent primary culture and three passages before being seeded into collagen scaffolds. These constructs were incubated for 1 week in an automated bioreactor using cyclic HP at 0–0.5 MPa, 0.5 Hz, and compared to constructs exposed to atmospheric pressure. In both groups, chondrogenic differentiation medium including transforming growth factor-β1 was employed. One, 2, 3, and 4 weeks after incubation, the cell constructs were harvested for histological, immunohistochemical, and gene expression evaluation.
Results: In histological and immunohistochemical analyzes, pericellular and extracellular metachromatic matrix was observed in both groups and increased over 4 weeks, but accumulated at a higher rate in the HP group. Cell number was maintained in the HP group over 4 weeks but decreased after 2 weeks in the atmospheric pressure group. Chondrogenic-specific gene expression of type II and X collagen, aggrecan, and SRY-box9 was increased in the HP group especially after 2 weeks.
Conclusion: Our results demonstrate chondrogenic differentiation of ASCs in a three-dimensional collagen scaffolds with treatment of a cyclic HP. Cyclic HP was effective in enhancing accumulation of extracellular matrix and expression of genes indicative of chondrogenic differentiation
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Combination of stromal cell-derived factor-1 and collagen-glycosaminoglycan scaffold delays contraction and accelerates reepithelialization of dermal wounds in wild-type mice
While dermal substitutes can mitigate scarring and wound contraction, a significant drawback of current dermal replacement technologies is the apparent delay in vascular ingrowth compared with conventional skin grafts. Herein, we examined the effect of the chemokine stromal cell-derived factor-1 (SDF-1) on the performance of a porous collagen–glycosaminoglycan dermal analog in excisional wounds in mice. C57BL/6 mice with 1 cm × 1 cm dorsal full-thickness wounds were covered with a collagen–glycosaminoglycan scaffold, followed by four daily topical applications of 1 μg SDF-1 or phosphate-buffered saline vehicle. Some animals were also pretreated with five daily doses of 300 mg/kg granulocyte colony-stimulating factor. Animals treated with SDF-1 and no granulocyte colony-stimulating factor reepithelialized 36% faster than vehicle controls (16 vs. 25 days), and exhibited less wound contraction on postwounding day 18 (∼35% greater wound area) plus three-fold longer neoepidermis formed than controls. Conversely, granulocyte colony-stimulating factor promoted contraction and no epidermal regeneration. Early (postwounding Day 3) inflammatory cell infiltration in the SDF-1-treated group was 86% less, while the fraction of proliferating cells (positive Ki67 staining) was 32% more, when compared with controls. These results suggest that SDF-1 simultaneously delays contraction and promotes reepithelialization and may improve the wound-healing performance of skin substitutes
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Tumors Stimulate Platelet Delivery of Angiogenic Factors in Vivo
The interaction between platelets and the tumor microenvironment results in the modulation of angiogenesis, although the mechanisms governing this regulation remain unclear. This study explores the differences in the communication between wounded tissues and healthy, tumor-conditioned, and frozen platelets. Platelet-rich plasma obtained from healthy (PRP) or tumor-bearing (TPRP) mice was applied to dorsal, full-thickness wounds on diabetic mice. Wound healing was evaluated using macroscopic criteria and a staging system based on angiogenesis and stromal cell proliferation. Proteomic analysis was used to compare the levels of angiogenic proteins contained in the platelet preparations. TPRP-treated wounds reached 90% wound closure 5.6 to 9.5 days earlier than PRP-treated and nontreated wounds, respectively. TPRP induced a fourfold increase in stromal cell proliferation compared with nontreated wounds, and a 2.5-fold increase compared with PRP-treated wounds. TPRP induced the highest stimulation of angiogenesis with a fourfold increase compared with nontreated controls. On day 21, wounds treated with TPRP showed a typical architecture with thick collagen bundles. Although the levels of angiogenesis regulators detected via SELDI-ToF were similar between the PRP and TPRP treatment regimens, the enhanced healing capacity of TPRP suggests improved platelet delivery as indicated by frozen TPRP preparations that had lost most of their pro-angiogenic drive. In conclusion, these results show that intact tumor-conditioned platelets display an improved ability to deliver angiogenesis regulators to wounded tissues
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Organized Skin Structure Is Regenerated In Vivo from Collagen-GAG Matrices Seeded with Autologous Keratinocytes
A well-characterized collagen-glycosaminoglycan matrix (CGM) that has been shown to function as a dermal analog was seeded with freshly disaggregated autologous keratinocytes and applied to full-thickness wounds in a porcine model. CGM were impregnated with 50,000 keratinocytes per cm2, a seeding density that produces a confluent epidermis within 19 d post-grafting and affords a 60-fold surface expansion of the donor epidermis. In this study, the temporal sequence of events in epidermal and neodermal formation was analyzed histopathologically and immunohistochemically from 4 to 35 d post-grafting. The epidermis was observed to form from clonal growth of individual keratinocytes into epithelial cords and islands that gradually enlarged, coalesced, differentiated to form large horn cysts, and finally reorganized at the graft surface to form a fully differentiated, normally oriented epidermis with rete ridges. Simultaneously, a neodermis formed from migration of endothelial cells, fibroblasts, and macrophages into the CGM from the underlying wound bed, resulting in formation of blood vessels, the production of abundant extracellular matrix, and the degradation of the CGM fibers, respectively. Gradually, the stromal cellularity of the CGM decreased and collagen deposition and remodeling increased to form a neodermal connective tissue matrix beneath the newly formed epidermis. Complete dissolution of the CGM occurred, partly as a result of degradation by an ongoing foreign-body giant cell reaction that peaked at 8–12 d post-grafting, but neither acute inflammation nor evidence of immune stimulation were observed. Within 1 mo, many structural components of normal skin were reconstituted