Neuropeptide Y (NPY) has been implicated in the regulation of cellular motility under various physiological and pathological conditions, including cancer dissemination. Yet, the exact signaling pathways leading to these effects remain unknown. In a pediatric malignancy, neuroblastoma (NB), high NPY release from tumor tissue associates with metastatic disease. Here, we have shown that NPY stimulates NB cell motility and invasiveness and acts as a chemotactic factor for NB cells. We have also identified the Y5 receptor (Y5R) as the main NPY receptor mediating these actions. In NB tissues and cell cultures, Y5R is highly expressed in migratory cells and accumulates in regions of high RhoA activity and dynamic cytoskeleton remodeling. Y5R stimulation activates RhoA and results in Y5R/RhoA-GTP interactions, as shown by pull-down and proximity ligation assays, respectively. This is the first demonstration of the role for the NPY/Y5R axis in RhoA activation and the subsequent cytoskeleton remodeling facilitating cell movement. These findings implicate Y5R as a target in anti-metastatic therapies for NB and other cancers expressing this receptor.

Background: Permanent sterilization is one of the most common methods of birth control in the United States and around the world. A small subset of women will regret their decision and desire future fertility. For these women, the options include in vitro fertilization (IVF) or surgical reversal. Surgical reversal, specifically via tubal reanastamosis, is an important choice to consider. Surgical reversal can be accomplished via three different general approaches including laparotomy, conventional laparoscopy, and robot-assisted approaches. Unfortunately, surgical reversal is becoming a lost art. Objective: To compare and contrast pregnancy success rates, ectopic pregnancy rates, and cost between the surgical methods and IVF. Methods: We conducted a literature review via Pubmed with keywords as listed below. Conclusion: Laparoscopic tubal reanastomosis is the best approach for women <40 years of age due to pregnancy outcomes that are comparable to other methods, cost effectiveness, and favorable safety profile of minimally invasive surgery.

Outpatient gynecologic surgeries are very common; in 2014 alone, 500,000 procedures were performed with 70% and 85% of hysterectomies and oophorectomies, respectively, performed in the outpatient setting. Although risk factors for overnight or prolonged admission after outpatient hysterectomy have been studied, less is known about the postoperative emergency department (ED) burden generated by other outpatient gynecologic surgeries.The objective of this retrospective cohort study was to identify the incidence of ED visits within 30 days of outpatient gynecologic surgery and to identify risk factors for these visits. This study included all adult patients undergoing scheduled outpatient gynecologic surgery for a benign condition at the Vanderbilt University Medical Center (VUMC), a tertiary academic medical institution, between January 2018 and September 2019. Demographic data, as well as comorbidities, surgical history, and surgical outcomes data, were obtained from the electronic medical record. Primary procedure performed was characterized into 1 of 4 categories: hysterectomy, other intra-abdominal nonprolapse surgery, prolapse surgery without hysterectomy, or other nonprolapse vulvovaginal procedure. The primary study outcome was evaluation in the VUMC ED within 30 days of surgery. Logistic regression models were used to evaluate associations between potential risk factors and the risk of an ED visit.A total of 2373 surgeries met the inclusion criteria, with 109 patients (5%) visiting the VUMC ED for a total of 125 visits within 30 days of surgery. After adjustment for potential confounders, younger age (adjusted odds ratio [aOR], 1.2; 95% confidence interval [CI], 1.1–1.3; P < 0.001), history of abdominal surgery (aOR, 1.7; 95% CI, 1.1–2.6; P = 0.02), cardiopulmonary comorbidities (aOR, 1.9; 95% CI, 1.2–3.0; P = 0.004), undergoing hysterectomy (aOR, 2.0; 95% CI, 1.1–3.8; P = 0.03), and a vulvovaginal surgical route as opposed to abdominal surgical route (aOR, 2.4; 95% CI, 1.2–5.1; P = 0.02) were all related to an increased risk of visiting the emergency room. Patients who visited the ED were more likely to have undergone hysterectomy (26% vs 20%, P = 0.05) and less likely to have undergone prolapse surgery (4% vs 12%, P = 0.05). The median time to first ED presentation was 7 days following surgery and surgical site pain (n = 52 [42% of visits]), nausea and/or vomiting (n = 18 [14%]), and fever (n = 15 [12%]) were the most common chief complaints. Of the 125 visits, 45 (36%) resulted in admission, and 36 of these (80%) were surgery related.The results of this study demonstrate that although ED visits after outpatient gynecologic surgery are uncommon, younger patients with underlying cardiopulmonary comorbidities and/or a history of abdominal surgery are at greater risk.

Fructose (Frc) is metabolized differently from glucose, i.e., with initial metabolism by ketohexokinase (KHK), an enzyme associated with ATP depletion. To test whether a diet enriched in Frc might impair energy‐intensive actions of the renal thick ascending limb (TAL), we evaluated TAL function and protein expression in response to 4‐weeks of 10% Frc in drinking water in young (Y, 3 months) male (M) and female (F) and mid‐aged F (A, 12 months) mice. Frc resulted in, on average, 11% lower kidney weights, regardless of age or sex. In addition, Frc caused a significant reduction in urine concentrating capacity, observed most dramatically in the aged females (F). Urine osmolality was (% of control): 95, 75, and 44 in YMFrc, YFFrc, and AFFrc, respectively. In contrast, Frc increased urine diluting capacity. However, this protective adaptation was attenuated in the AFFrc (urine osmolality % of C): 77 (YMFrc), 76 (YFFrc), 87 (AFFrc). Western blotting revealed 2–5X increased kidney cortex KHK expression in Frc groups, with the increase greatest in YFFrc. Frc resulted in a modest 20–60% increase in band density for the Na‐K‐2Cl cotransporter (NKCC2), the major apical sodium chloride cotransporter of the TAL, but only in Y mice. In the AFFrc it was reduced 30%. In summary, diets enriched in Frc may alter the ability of the TAL to effectively dilute and concentrate urine. Aging subjects may be especially vulnerable. NIH DK082507.

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