James Liu

A novel enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to HIV-1 envelope glycoproteins based on immobilization of viral glycoproteins in microtiter wells coated with concanavalin A.

We have developed a novel method that greatly simplifies the preparation of solid-phase HIV-1 envelope glycoproteins for use in an ELISA that detects serum antibodies to HIV envelope antigens. This method utilizes concanavalin A absorbed to wells of microtiter plates to affinity immobilize detergent-solubilized viral glycoproteins released in culture fluids of HIV-1 infected cell lines grown in serum free medium. Antibodies binding to ConA-immobilized viral antigens are detected by peroxidase-conjugated antibodies and appropriate enzyme substrates. Unlike most commercial HIV ELISAs, which utilize gp120 depleted-purified virus as the source of antigens and thus favor detection of antibodies to core antigens, the ConA envELISA is highly sensitive for detecting antibodies to native gp120, as evidenced by the strong reactivity of gp120-specific human monoclonal antibodies. Our results also suggest that representation of gp41 in the assay varies and depends on which virus infected cell lines are used for antigen production. Since this assay accurately identified 14 HIV-1 antibody positive patient sera and no false positives were detected among 16 HIV-1 negative sera, the ConA envELISA shows promise as an inexpensive assay for the serologic diagnosis of HIV infections.

Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.

Robotic Partial Nephrectomy for Clinical Stage T1b Tumors: Intermediate Oncologic and Functional Outcomes

OBJECTIVE The objective of this study was to examine our intermediate oncologic and functional outcomes of robotic partial nephrectomy for clinical T1b tumors. Partial nephrectomy has become the gold standard of treatment for small renal masses. Recently, indications for minimally invasive partial nephrectomy have extended to larger and more complicated renal masses in some centers. MATERIALS AND METHODS Between July 2008 and September 2013, 241 robotic partial nephrectomies were performed at our institution, including 46 for clinical ≥ T1b tumors. We reviewed the intermediate-term functional and oncologic outcomes of this cohort of patients. RESULTS Of the 46 patients, the median age was 55.5 years (interquartile range [IQR], 51-68 years) with a median body mass index of 31.6 (IQR, 27.4-38.9), tumor diameter of 5.0 cm (IQR, 4.1-5.2 cm), and RENAL nephrometry score of 7.1 (range, 5-11). Renal cell carcinoma was confirmed in 35 patients, and 11 patients had benign pathology. There was 1 patient with an established positive margin and 2 patients had a focal positive margin. At a median follow-up of 24.3 months (range, 2.3-61.1 months), the overall, recurrence-free and cancer-specific survival was 97.1%, 97.1%, and 100%, respectively. No patient progressed to dialysis postoperatively and there was no significant difference between preoperative and postoperative serum creatinine or estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation. CONCLUSION Because of the many adverse medical effects of chronic renal insufficiency, the indications for partial nephrectomy are expanding at many institutions. We demonstrated that robotic partial nephrectomy is a safe and efficacious procedure for the treatment of T1b renal tumors with excellent intermediate oncologic and functional outcomes.

Nanotechnology applications in urology: a review

The objectives of this review are to discuss the current literature and summarise some of the promising areas with which nanotechnology may improve urological care. A Medline literature search was performed to elucidate all relevant studies of nanotechnology with specific attention to its application in urology. Urological applications of nanotechnology include its use in medical imaging, gene therapy, drug delivery, and photothermal ablation of tumours. In vitro and animal studies have shown initial encouraging results. Further study of nanotechnology for urological applications is warranted to bridge the gap between preclinical studies and translation into clinical practice, but nanomedicine has shown significant potential to improve urological patient care.

Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in a murine model.

To investigate tyrosine kinase inhibitors (TKI) and gold nanorods (AuNRs) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma (RCC) mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urological cancers. Likewise, the use of nanoparticles in photothermal tumour ablation, although early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNRs and activated with photothermal ablation have shown significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model.

Nondestructive Diagnosis of Kidney Cancer on 18-gauge Core Needle Renal Biopsy Using Dual-color Fluorescence Structured Illumination Microscopy.

OBJECTIVE To present a novel imaging technique used for rapid, nondestructive histological assessment of renal neoplasias using a dual-component fluorescence stain and structured illumination microscopy (SIM). MATERIALS AND METHODS After Institutional Review Board approval, 65 total biopsies were obtained from 19 patients undergoing partial or radical nephrectomy. Biopsies were stained with a dual-component fluorescent, and optically sectioned SIM images were obtained from the surface of the intact biopsies. Specimens were subsequently fixed and analyzed using hematoxylin and eosin (H&E) histopathologic methods and compared with SIM images. A single, board-certified pathologist blinded to specimens reviewed all SIM images and H&E slides, and determined the presence or absence of neoplasias. Results of blinded diagnosis of SIM were validated against traditional pathology. RESULTS Of the 19 patients, 15 underwent robotic partial nephrectomies and 4 underwent laparoscopic nephrectomies. Indications included clinical suspicion of renal cell carcinoma. In total, 65 biopsy specimens were available for review. Twenty-one specimens were determined to be neoplastic on H&E, whereas 41 represented benign renal tissue. The final sensitivity and specificity of our study were 79.2% and 95.1%, respectively. CONCLUSION SIM is a promising technology for rapid, near-patient, ex vivo renal biopsy assessment. By improving the ability to rapidly assess sufficiency of biopsy specimens and enabling immediate diagnostic capability, SIM aids in more effective biopsy performance, tissue triage, and patient counseling regarding management options. Additionally, because tissue is preserved, effective utilization of downstream diagnostic tests and molecular assessments are possible.

Stratification of Expert vs Novice Laparoscopists Using the Basic Laparoscopic Urologic Surgery (BLUS) Curriculum at a Single Institution

PURPOSE To assess determinants of performance applying the tasks of the Basic Laparoscopic Urologic Surgery (BLUS) skills curriculum administered at a single institution. METHODS After obtaining institutional review board approval, fourth-year medical students, urology residents (postgraduate year 1-5), and staff attending surgeons from an academic institution were recruited. Participants were grouped by level of experience and evaluated on 4 different BLUS modules testing fundamental laparoscopic techniques from September 2012 to September 2013. Task completion time (TCT) and missed objectives were compared with previous laparoscopic experience, amount of endourological training, and scores obtained through the EDGE simulator. RESULTS TCTs among the participants were slower and accrued greater errors in the novice group (n = 10) than in the intermediate-level (n = 9) and expert-level (n = 9) groups. Completion times on the peg transfer were 213.4, 128.1, and 108.7 seconds (p < 0.05); on the circle cutting were 182.4, 128.3, and 97.2 seconds (p < 0.05); on the clip application were 44.4, 43.2, and 38.1 seconds (p = 0.08); and on the suturing were 286.1, 177.3, and 123.6 seconds (p < 0.05) for novice, intermediate, and expert groups, respectively. When past laparoscopic numbers of participants were compared with TCTs, a positive correlation of R(2) = 0.39 was seen, signifying a relationship between number of laparoscopic cases and TCT outcomes. CONCLUSION Performance on the EDGE simulator device during the BLUS modules significantly correlated with the amount of laparoscopic experience. Increase in the years of experience and number of laparoscopic cases led to faster and more accurate TCTs.

Failure Analysis of Multilayered Suspension Plasma-Sprayed Thermal Barrier Coatings for Gas Turbine Applications

Improvement in the performance of thermal barrier coatings (TBCs) is one of the key objectives for further development of gas turbine applications. The material most commonly used as TBC topcoat is yttria-stabilized zirconia (YSZ). However, the usage of YSZ is limited by the operating temperature range which in turn restricts the engine efficiency. Materials such as pyrochlores, perovskites, rare earth garnets are suitable candidates which could replace YSZ as they exhibit lower thermal conductivity and higher phase stability at elevated temperatures. The objective of this work was to investigate different multilayered TBCs consisting of advanced topcoat materials fabricated by suspension plasma spraying (SPS). The investigated topcoat materials were YSZ, dysprosia-stabilized zirconia, gadolinium zirconate, and ceria–yttria-stabilized zirconia. All topcoats were deposited by TriplexPro-210TM plasma spray gun and radial injection of suspension. Lifetime of these samples was examined by thermal cyclic fatigue and thermal shock testing. Microstructure analysis of as-sprayed and failed specimens was performed with scanning electron microscope. The failure mechanisms in each case have been discussed in this article. The results show that SPS could be a promising route to produce multilayered TBCs for high-temperature applications.

Nanotechnology in Urology: History of Development and Applications in Urology

In 1959, future Nobel Laureate (1965) Dr. Richard Feynman presented a landmark lecture entitled “There’s Plenty of Room at the Bottom” to the American Physical Society where he postulated the miniaturization of science and challenged the audience: “How small can you make machinery?” Dr. Feynman’s early visions and conceptual thoughts of shrinking down our understanding of the physical realm and examining the elemental parts on a small scale was the earliest invitation for our exploration into the realm of nanotechnology [1].

Chapter 35 – Posttraumatic Stress Disorder and Its Effects on Men’s Sexual and Reproductive Health

Abstract Posttraumatic stress disorder (PTSD) is a complex somatic, cognitive, and behavioral condition that occurs following traumatic events. Patients with PTSD often exhibit intrusive thoughts, nightmares, flashbacks of past traumatic events, hypervigilance, avoidance of reminders of trauma, and sleep disturbance, all of which can lead to significant occupational and interpersonal dysfunction. The constellation of symptoms associated with PTSD has been well documented in the Diagnostic and Statistical Manual of Mental Disorders; however, the effects of PTSD on sexual function have not been well characterized. PTSD can have detrimental effects on intimacy and sexual health that range from decreased sexual desire and impotence to impaired fertility. Therefore, it is critical that physicians appropriately screen patients with PTSD for sexual dysfunction, as well as consider factors such as substance abuse, iatrogenic medication side effects, and avoidance of intimacy and sex due to undertreated psychiatric illness, which can complicate management of these patients. This chapter describes the biology and pathophysiology of PTSD in relation to men’s sexual and reproductive health, with a focus on guiding physicians in the proper management of such difficult patients.