Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitors (PIs) are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic activities through non-competitive binding to PR, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS) system, thus increasing the chances of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of fission yeast as a possible surrogate system to study the effects of HIV-1 protease on cellular functions and to explore its utility as a HTS system to search for new PIs to battle HIV-1 resistant strains.

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Treatment of testicular cancer has made significant progress in the past decades in terms of reduction of treatment-associated morbidity and preventing over-treatment. At the forefront of this progression is utilization of the da Vinci robot to perform retroperitoneal lymph node dissections (RPLNDs) via a minimally invasive approach. The robot offers multiple potential advantages such as smaller incisions, improved 3D visualization, more precise dissection, and faster convalescence, leading to its increased usage the past several years. In this chapter, we summarize the recent progress made in robotic surgery for testicular cancer and its potential in the future. Promising preliminary data has also renewed interest in defining the role of primary RPLND in patients with seminoma, potentially sparing patients of the harmful long-term radiation and cisplatin-based chemotherapy. SEMS and PRIMETEST trials are ongoing trials that will provide significant insight into this area and potentially expand the role of robotic RPLND.

Background: Ureteroarterial fistulas (UAFs) are rare life-threatening complications of indwelling ureteral stents. Endovascular repair of these fistulas is now commonly used but the long-term outcomes are unknown.Case Presentation: We present a 51-year-old African American female with history of cervical cancer status after a hysterectomy and radiation. She has bilateral ureteral strictures that were managed with chronic, indwelling ureteral stents. She subsequently developed a right UAF and was treated with an endovascular stent to the external iliac artery. After 2 years, she subsequently developed hematuria and hematochezia and was found to have a uretero-arterial-enteric fistula. We performed an exploratory laparotomy and repair of the fistula. The patient was subsequently managed with indwelling nephrostomy tubes and had no further episodes of bleeding.Conclusion: To our knowledge, this is the first reported case of uretero-arterial-enteric fistula after endovascular treatment of UAF. Our experience demonstrates the need for a high index of suspicion and close surveillance after treatment for patients with UAF.

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