Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs). Exosomes contain proteins, micro RNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC) patients can serve as biomarkers. lncRNAs are > 200 nucleotide long transcripts that do not encode protein and play critical roles in tumor biology. As the number of recognized tumor-associated lncRNAs continues to increase, there is a parallel need to include lncRNAs into biomarker discovery and therapeutic target algorithms. The lncRNA HOX transcript antisense RNA (HOTAIR) has been shown to facilitate tumor initiation and progression and is associated with poor prognosis in several cancers. The importance of HOTAIR in cancer biology has sparked interest in using HOTAIR as a biomarker and potential therapeutic target. Here we show HOTAIR and several tumor-associated lncRNAs are enriched in UEs from UBC patients with high-grade muscle-invasive disease (HGMI pT2-pT4). Knockdown of HOTAIR in UBC cell lines reduces in vitro migration and invasion. Importantly, loss of HOTAIR expression in UBC cell lines alters expression of epithelial-to-mesenchyme transition (EMT) genes including SNAI1, TWIST1, ZEB1, ZO1, MMP1 LAMB3, and LAMC2. Finally, we used RNA-sequencing to identify four additional lncRNAs enriched in UBC patient UEs. These data, suggest that UE-derived lncRNA may potentially serve as biomarkers and therapeutic targets.

In a population which had passed SBT, the ability of the traditional weaning indices to discriminate between children successfully extubated and children re-intubated is very poor.

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Priapism is a pathologic erection lasting >4 hours that is unrelated to or persists beyond sexual stimulation. Priapism is rare in children, and rarely reported in infants. Although a small number of cases have been reported in neonates, even fewer have been reported in infants outside of the neonatal period. Due to its rarity and poorly understood pathophysiology, the diagnosis and management of priapism in infants is challenging. We report a rare case of idiopathic non-ischemic priapism in a 9-month-old highlighting some of the challenges in diagnosis and management of priapism in this age group.

P atients with the most malignant type of glioma, Grade IV glioblastoma, have a mean survival time of approximately 15 months and an estimated 5-year survival rate of less than 5%.11 High-grade gliomas (Grades III and IV) are the most common primary brain tumors in adults and the fourth leading cause of cancerrelated death. 40 Tumor hypoxia is thought to play an important role in glioblastoma tumor pathobiology by proabbreviatioNs CA-IX = carbonic anhydrase-IX; CED = convection-enhanced delivery; DAB = 3,3′-diaminobenzidine tetrahydrochloride; DCA = dichloroacetate; EHCO = 1-(aminoethyl)iminobis [N-(oleicylcysteinylhistinyl-1-aminoethyl)propionamide]; GFP = green fluorescent protein; GLUT-1 = glucose transporter 1; HIF-1a = hypoxia-inducible factor 1a; IHC = immunohistochemistry; MVD = microvascular density; PEG = polyethylene glycol; PI = proliferation index; RNAi = RNA interference; siRNA = small interfering RNA; VEGF = vascular endothelial growth factor. obJeCt High-grade gliomas are the most common form of adult brain cancer, and patients have a dismal survival rate despite aggressive therapeutic measures. Intratumoral hypoxia is thought to be a main contributor to tumorigenesis and angiogenesis of these tumors. Because hypoxia-inducible factor 1a (HIF-1a) is the major mediator of hypoxia-regulated cellular control, inhibition of this transcription factor may reduce glioblastoma growth. MetHoDs Using an orthotopic mouse model with U87-LucNeo cells, the authors used RNA interference to knock down HIF-1a in vivo. The small interfering RNA (siRNA) was packaged using a novel multifunctional surfactant, 1-(amino ethyl)iminobis[N-(oleicylcysteinylhistinyl-1-aminoethyl)propionamide] (EHCO), a nucleic acid carrier that facilitates cellular uptake and intracellular release of siRNA. Stereotactic injection was used to deliver siRNA locally through a guide-screw system, and delivery/uptake was verified by imaging of fluorescently labeled siRNA. Osmotic pumps were used for extended siRNA delivery to model a commonly used human intracranial drug-delivery technique, convectionenhanced delivery. resUlts Mice receiving daily siRNA injections targeting HIF-1a had a 79% lower tumor volume after 50 days of treatment than the controls. Levels of the HIF-1 transcriptional targets vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT-1), c-MET, and carbonic anhydrase-IX (CA-IX) and markers for cell growth (MIB-1 and microvascular density) were also significantly lower. Altering the carrier EHCO by adding polyethylene glycol significantly increased the efficacy of drug delivery and subsequent survival. CoNClUsioNs Treating glioblastoma with siRNA targeting HIF-1a in vivo can significantly reduce tumor growth and increase survival in an intracranial mouse model, a finding that has direct clinical implications.

There has been a major shift from the old paradigm of 'see one, do one, teach one' in medical training due in large part to resident work-hour restrictions and required oversight in the operating room. In response to this, advancements in technology have allowed for the introduction of more objective measures to assess the skill competency and proficiency of surgical trainees. Patient safety and trainee well-being are important drivers for this new model, and so surgical training programs are adopting simulation into their curriculum. Urology is uniquely positioned at the forefront of new emerging technologies in surgery, because of the field's commitment to safe and efficient minimally invasive surgery and endourological procedures. Due to these technically challenging procedures, urological training must incorporate these educational technologies to allow for objective skills assessment, skills transfer, and ultimately providing optimal patient care with the production of proficient and competent urological trainees.

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IntroductionExtramedullary plasmacytoma is a rare plasma cell neoplasm. Plasmacytomas are most commonly found in the head and neck region, but can occur in many other locations. They rarely occur in the testis, and are commonly associated with concurrent multiple myeloma at the time of diagnosis. Isolated plasmacytoma of the testis is exceedingly rare, with few cases reported in the literature.Case presentationA 72-year-old Caucasian man presented with a painless testicular mass treated by orchiectomy. The mass was determined to be plasmacytoma on pathological examination. At the time of diagnosis, our patient did not have multiple myeloma, and is currently undergoing chemotherapy for treatment of his disease.ConclusionIsolated plasmacytoma of the testicle is a rare cause of testicular mass, and is seldom reported in the literature. Patients with this disease require careful monitoring because of their high risk of progression to multiple myeloma. The diagnosis of testicular plasmacytoma can be challenging for primary care doctors and urologic specialists. This condition should be in the differential diagnosis in elderly men.