Make Art Real

The Make Art Real project aims to introduce new audiences to the arts. It supports Theme II of VCU’s Quest for Distinction by promoting and fostering creative expression through innovative collaborations. The project involves displaying existing connections between art and non-art disciplines, as well as making new connections. These unusual pairings are then placed on exhibition through a lunch-time lecture series named “Unexpected_Connections,” which allow faculty, staff, and students to lead and participate in discussions about the reality of art. The lecture series is the first sustainable and reoccurring program to be held in the Depot building, a multidisciplinary facility which is intended to foster interdisciplinary collaborations. The targeted audience includes faculty, staff, students, and members of the greater VCU community

Short-course antiretroviral therapy in primary HIV infection

Background Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. Methods We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. Results A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average followup of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P = 0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P = 0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P = 0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log10 copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. Conclusions A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.

Radiostereometric Analysis of Tantalum vs. Titanium Acetabular Shells in Young THR Patients

Introduction: In the active total hip replacement (THR) population, maintaining acetabular component stability and limiting polyethylene wear are crucial components to preventing premature implant failure. Titanium with Co/Cr/Mo fiber metal coating is among the most common materials used in cementless THR. Trabecular metal, composed of porous tantalum, has a metallic strut design resembling trabecular bone, designed to improve tissue infiltration and limit migration. This study assesses the stability and clinical outcomes of tantalum versus titanium acetabular shells using radiostereometric analysis (RSA) technology. Methods: In this IRB approved, prospective, randomized, blinded study, 46 patients received a primary THR by a single surgeon (DCA). Each patient was randomized to receive a titanium (23) (Trilogy, Zimmer) or tantalum (23) (Modular tantalum shell, Zimmer) uncemented hemispheric cup and either a highly-crosslinked or conventional polyethylene liner. Tantalum RSA markers were implanted around the liner periphery, femur, and periacetabular bone in each patient. RSA examinations, Harris Hip, UCLA, WOMAC, SF-36 scores were obtained at 10 days, 6 months, and annually with the furthest patients evaluated through 5 years. Results: Median translation was greater at all time points for the tantalum mesh cups except for the 3-year follow-up, however due to large standard errors, there was no significant difference between the two designs (p\u3e0.05). These large standard errors were predominantly caused by two outliers, neither of which had clinical evidence of loosening at 5 years follow-up. Mean UCLA, WOMAC, Harris Hip, and SF-36 PCS and MCS scores improved similarly in both groups. Conclusions: In this young THR population, both titanium and tantalum acetabular shells demonstrated excellent stability at five years follow up. Tantalum shells demonstrated slightly greater micromotion, but there was no statistically significant difference in shell migration. Outstanding clinical outcomes with statistically significant improvements in function and pain relief were observed in both groups

Radiostereometric Analysis of Femoral Head Penetration in Cross-Linked Polyethylene in THR Patients

Background: In the young total hip replacement (THR) population limiting polyethylene liner wear is crucial to preventing premature implant failure. Highly cross-linked ultra-high molecular weight polyethylene (HXLPE) liners were designed to improve wear resistance of polyethylene liners. Radiostereometric analysis (RSA) provides highly precise measurements of liner wear. This study utilized RSA to characterize wear of conventional versus HXLPE liners up to five years following THR. Methods: This IRB-approved, prospective, randomized, blinded study, involved 46 patients with a mean age of 58 and BMI of 30. Each patient was double randomized to receive a conventional or HXLPE liner with an uncemented titanium mesh or tantalum trabecular metal cup. Both liners were prepared from compression-molded GUR 1050 resin without calcium stearate, while HXLPE liners undergo further e-beam irradiation and annealing. At the time of surgery, 1mm tantalum RSA markers were implanted around the liner periphery, femur and periacetabular bone. RSA examinations, Harris Hip, UCLA, WOMAC, SF-36 scores were obtained pre-operatively, post-operatively, at six weeks, six months and annually through five years. Results: All patients had statistically significant improvement in Harris Hip, WOMAC and SF-36 PCS scores following THR with no difference between cohorts. On RSA examination, of titanium shells, HXLPE liners revealed significantly lower femoral head penetration at each follow up except six weeks and six months (p Conclusion: In this young THR population RSA shows significantly less femoral head penetration in the HXLPE liners compared to conventional liners. Novel RSA techniques have been developed to determine polyethylene wear in patients

Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature

Acknowledgements The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC) (S3802ASA) and the generous support of the Martin Family Foundation for funding the Ph.D. studentships of P. S. and A. L., respectively. This work was also partially funded through a US-Ireland R&D Partnership grant awarded by HSCNI (STL/5010/14), Medical Research Council UK (MC_PC_15013), and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R009112/1).Peer reviewedPublisher PD

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator