Eric F. Swart

Bio: Eric F. Swart is an academic researcher from University of Massachusetts Amherst. The author has contributed to research in topics: Ankle & Toddler's fracture. The author has an hindex of 17, co-authored 79 publications receiving 1187 citations. Previous affiliations of Eric F. Swart include Carolinas Medical Center & University of Massachusetts Medical School.

In vitro analysis of a hepatic device with intrinsic microvascular-based channels

Abstract: A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.

Murine B16 Melanomas Expressing High Levels of the Chemokine Stromal-Derived Factor-1/CXCL12 Induce Tumor-Specific T Cell Chemorepulsion and Escape from Immune Control

Abstract: The chemokine, stromal-derived factor-1/CXCL12, is expressed by normal and neoplastic tissues and is involved in tumor growth, metastasis, and modulation of tumor immunity. T cell-mediated tumor immunity depends on the migration and colocalization of CTL with tumor cells, a process regulated by chemokines and adhesion molecules. It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis. We proposed that repulsion of tumor Ag-specific T cells from a tumor expressing high levels of CXCL12 allows the tumor to evade immune control. Murine B16/OVA melanoma cells (H2b) were engineered to constitutively express CXCL12. Immunization of C57BL/6 mice with B16/OVA cells lead to destruction of B16/OVA tumors expressing no or low levels of CXCL12 but not tumors expressing high levels of the chemokine. Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100. Memory OVA-specific CD8+ T cells demonstrated antitumor activity against B16/OVA tumors but not B16/OVA.CXCL12-high tumors. Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner. The repulsion of tumor Ag-specific T cells away from melanomas expressing CXCL12 confirms the chemorepellent activity of high concentrations of CXCL12 and may represent a novel mechanism by which certain tumors evade the immune system.

Widespread Implementation of Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Instability Maintains Functional Outcomes at Midterm to Long-Term Follow-up While Decreasing Complication Rates: A Systematic Review

Abstract: Purpose Our primary purpose was to evaluate whether complications have increased or functional outcomes have changed as medial patellofemoral ligament (MPFL) reconstruction has been adopted by more surgeons at more institutions over recent years. Our secondary purpose was to further define the complication profile of MPFL reconstruction. Methods A systematic review of the literature was performed on January 12, 2014, using the keywords "medial patellofemoral ligament reconstruction," "patellar instability reconstruction," "patellofemoral ligament reconstruction," and "MPFL." Articles meeting our inclusion criteria were reviewed. Outcome measures, functional failures, complications, graft choice, and surgical technique were recorded and analyzed. Results Thirty-four articles met our exclusion and inclusion criteria and were reviewed. Nineteen articles were "new" additions to the literature, whereas 15 had previously been reported on in prior analyses ("old"). The 19 new articles reported a statistically significant decrease in functional failure rates, from 9.55% in older studies to 4.77% in more recent studies ( P P = .005), and the minor complication rate decreased from 6.53% to 4.00% ( P = .06). Postoperative Kujala scores did not show a statistically significant change between newer and older publications (89.0 [SD, 3.7] and 89.4 [SD, 4.9], respectively; P = .55). Comparing results by fixation type, as well as by graft choice, showed no statistically significant differences in terms of outcomes or complication profile. Conclusions With nearly twice the number of medical centers performing reconstruction of the MPFL and outcomes reported on nearly double the number of patients in recent years, functional outcomes remain favorable as complication and failure profiles are improving. Furthermore, despite a wide array of fixation techniques, as well as multiple options for graft constructs, there are no statistically or clinically significant differences in functional outcomes over time. This finding highlights the efficacy and adoptability of MPFL reconstruction for the treatment of recurrent patellar instability. Level of Evidence Level IV, systematic review of mixed-level studies.

Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes

Abstract: A major stumbling block for research on and treatment of type 1 diabetes is the inability to directly, but noninvasively, visualize the lymphocytic/inflammatory lesions in the pancreatic islets. One potential approach to surmounting this impediment is to exploit MRI of magnetic nanoparticles (MNP) to visualize changes in the microvasculature that invariably accompany inflammation. MNP-MRI did indeed detect vascular leakage in association with insulitis in murine models of type 1 diabetes, permitting noninvasive visualization of the inflammatory lesions in vivo in real time. We demonstrate, in proof-of-principle experiments, that this strategy allows one to predict, within 3 days of completing treatment with an anti-CD3 monoclonal antibody, which NOD mice with recent-onset diabetes are responding to therapy and may eventually be cured. Importantly, an essentially identical MNP-MRI strategy has previously been used with great success to image lymph node metastases in prostate cancer patients. This success strongly argues for rapid translation of these preclinical observations to prediction and/or stratification of type 1 diabetes and treatment of individuals with the disease; this would provide a crucially needed early predictor of response to therapy.

Prevention and Screening Programs for Anterior Cruciate Ligament Injuries in Young Athletes: A Cost-Effectiveness Analysis

Abstract: BACKGROUND: Anterior cruciate ligament (ACL) injuries are common among young athletes. Biomechanical studies have led to the development of training programs to improve neuromuscular control and reduce ACL injury rates as well as screening tools to identify athletes at higher risk for ACL injury. The purpose of this study was to evaluate the cost-effectiveness of these training methods and screening strategies for preventing ACL injuries. METHODS: A decision-analysis model was created to evaluate three strategies for a population of young athletes participating in organized sports: (1) no training or screening, (2) universal neuromuscular training, and (3) universal screening, with neuromuscular training for identified high-risk athletes only. Risk of injury, risk reduction from training, and sensitivity and specificity of screening were based on published data from clinical trials. Costs of training and screening programs were estimated on the basis of the literature. Sensitivity analyses were performed on key model parameters to evaluate their effect on base case conclusions. RESULTS: Universal neuromuscular training of all athletes was the dominant strategy, with better outcomes and lower costs compared with screening. On average, the implementation of a universal training program would save $100 per player per season, and would reduce the incidence of ACL injury from 3% to 1.1% per season. Screening was not cost-effective within the range of reported sensitivity and specificity values. CONCLUSIONS AND CLINICAL RELEVANCE: Given its low cost and ease of implementation, neuromuscular training of all young athletes represents a cost-effective strategy for reducing costs and morbidity from ACL injuries. While continued innovations on inexpensive and accurate screening methods to identify high-risk athletes remain of interest, improving existing training protocols and implementing neuromuscular training into routine training for all young athletes is warranted. Language: en

Medscape

Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Reconstituting Organ-Level Lung Functions on a Chip

Abstract: Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.

Microfluidic organs-on-chips

Abstract: Organ-level physiology is recapitulated in vitro by culturing cells in perfused, microfluidic devices.

Cancer immunotherapy via dendritic cells

Abstract: Cancer immunotherapy attempts to harness the power and specificity of the immune system to treat tumours. The molecular identification of human cancer-specific antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Owing to their properties, dendritic cells (DCs) are often called 'nature's adjuvants' and thus have become the natural agents for antigen delivery. After four decades of research, it is now clear that DCs are at the centre of the immune system owing to their ability to control both immune tolerance and immunity. Thus, DCs are an essential target in efforts to generate therapeutic immunity against cancer.