Glial loss of the metallo ß-lactamase domain containing protein, SWIP-10, induces age- and glutamate-signaling dependent, dopamine neuron degeneration.

Across phylogeny, glutamate (Glu) signaling plays a critical role in regulating neural excitability, thus supporting many complex behaviors. Perturbed synaptic and extrasynaptic Glu homeostasis in the human brain has been implicated in multiple neuropsychiatric and neurodegenerative disorders including Parkinson's disease, where theories suggest that excitotoxic insults may accelerate a naturally occurring process of dopamine (DA) neuron degeneration. In C. elegans, mutation of the glial expressed gene, swip-10, results in Glu-dependent DA neuron hyperexcitation that leads to elevated DA release, triggering DA signaling-dependent motor paralysis. Here, we demonstrate that swip-10 mutations induce premature and progressive DA neuron degeneration, with light and electron microscopy studies demonstrating the presence of dystrophic dendritic processes, as well as shrunken and/or missing cell soma. As with paralysis, DA neuron degeneration in swip-10 mutants is rescued by glial-specific, but not DA neuron-specific expression of wildtype swip-10, consistent with a cell non-autonomous mechanism. Genetic studies implicate the vesicular Glu transporter VGLU-3 and the cystine/Glu exchanger homolog AAT-1 as potential sources of Glu signaling supporting DA neuron degeneration. Degeneration can be significantly suppressed by mutations in the Ca2+ permeable Glu receptors, nmr-2 and glr-1, in genes that support intracellular Ca2+ signaling and Ca2+-dependent proteolysis, as well as genes involved in apoptotic cell death. Our studies suggest that Glu stimulation of nematode DA neurons in early larval stages, without the protective actions of SWIP-10, contributes to insults that ultimately drive DA neuron degeneration. The swip-10 model may provide an efficient platform for the identification of molecular mechanisms that enhance risk for Parkinson's disease and/or the identification of agents that can limit neurodegenerative disease progression.

Outcomes of Gastric Resection in the Establishment of a Comprehensive Oncologic Robotic Program.

BACKGROUND: Robotic-assisted gastrectomy is increasingly utilized for the treatment of gastric malignancies. However, the benefits of robotic surgery have been questioned. This study describes short-term outcomes in the establishment of a comprehensive robotic program for gastric malignancies. MATERIALS AND METHODS: Patients who underwent robotic-assisted gastric resections between 2013 and 2018 were studied. Preoperative measures and surgical outcomes were analyzed. Finally we studied and analyzed robotic and open gastrectomy for the management of gastric adenocarcinoma (GC) at the same institution between 2000 and 2018 for quality benchmarking. RESULTS: Forty six patients (pts.) underwent robotic-assisted gastric resections. 26 (56.5%) were male, with a median age of 62 y (range: 29-87). Pathology included GC, gastrointestinal stromal tumors, neuroendocrine tumors, metastatic lesions, and benign processes. 19 pts. underwent total gastrectomy, 16 distal gastrectomy, four subtotal gastrectomy, and seven wedge resection. Pts. undergoing distal gastrectomy and wedge resection experienced shorter operative times and length of stay than total gastrectomy (P < 0.01; P < 0.01). Four operations (8.8%) were converted to open and 13 pts (28.3%) had postoperative complications, including an 8.7% readmission rate. Median lymph nodes retrieved during total, subtotal, and distal gastrectomy were 20 (13-46), 12.5 (0-26), and 16.5 (0-34), respectively. All pts. underwent margin negative resection. Median follow-up for GC was 21 mo, and 60% of pts. received adjuvant therapy at a median of 59d (range: 23-106). CONCLUSIONS: Robotic gastrectomy is a feasible alternative to open gastrectomy. Our results will help establish benchmarks to improve perioperative outcomes, especially length of stay and time to initiation of therapy.

The Hidden Curriculum: Strategies for Preparing Residents for Practice.

PURPOSE OF REVIEW: The goal of this paper was to identify areas of importance in modern urology education that are not currently emphasized in current urological curricula. RECENT FINDINGS: We identified curricular deficits in robotic surgical simulation, transgender health, leadership, business management, and social media training. Few practicing urologists feel comfortable managing transgender-specific needs, and most training programs do not adequately address transgender health. Urology programs also do not sufficiently emphasize topics in leadership, business management, or appropriate social media usage. With respect to simulation, while it is currently included in the Accreditation Council for Graduate Medical Education (ACGME) program requirements, it is currently under-utilized for training in robotic surgery. It is important for urologists to receive adequate training for the modern practice landscape. Where knowledge gaps among early practicing urologists arise, programs should adapt their curricula to address them.

Exploring Gadolinium-Based Contrast Media for Retrograde Pyelography in the Context of Iodine Allergy.

Iodinated contrast media can rarely cause severe allergic reactions during nonvascular urologic imaging procedures. Alternatives like gadolinium-based contrast may help mitigate this risk in susceptible patients. A 66-year-old woman with a documented iodine allergy presented with an obstructing stone in the right ureter. To avoid the risk of an allergic reaction, the decision was made to use an alternative non-iodinated contrast agent for retrograde pyelography prior to ureteral stent placement. Gadobenate dimeglumine, an MRI contrast agent, was diluted 50:50 with saline and utilized successfully to provide adequate opacification for safe stent placement without adverse reaction. The patient underwent repeat pyelography with gadobenate dimeglumine one month later during ureteroscopy without complication. This case demonstrates that diluted gadobenate can serve as an effective alternative to iodinated contrast media in patients at high risk of reaction to iodine-containing agents. While severe reactions to iodinated contrast are uncommon in nonvascular urologic procedures, they can still occur even with premedication. Gadolinium-based agents have been reported to provide sufficient opacification for most urologic interventions, though inferior radiographically to iodinated contrast. Further study on gadolinium efficacy and safety in this setting is warranted. However the present case supports gadobenate dimeglumine as a viable option for retrograde pyelography when allergy risk precludes iodinated contrast use.