Chronic ethanol induces a pro-inflammatory switch in interleukin-1ß regulation of GABAergic signaling in the medial prefrontal cortex of male mice.

Neuroimmune pathways regulate brain function to influence complex behavior and play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD). In particular, the interleukin-1 (IL-1) system has emerged as a key regulator of the brain's response to ethanol (alcohol). Here we investigated the mechanisms underlying ethanol-induced neuroadaptation of IL-1ß signaling at GABAergic synapses in the prelimbic region of the medial prefrontal cortex (mPFC), an area responsible for integrating contextual information to mediate conflicting motivational drives. We exposed C57BL/6J male mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and conducted ex vivo electrophysiology and molecular analyses. We found that the IL-1 system regulates basal mPFC function through its actions at inhibitory synapses on prelimbic layer 2/3 pyramidal neurons. IL-1ß can selectively recruit either neuroprotective (PI3K/Akt) or pro-inflammatory (MyD88/p38 MAPK) mechanisms to produce opposing synaptic effects. In ethanol naïve conditions, there was a strong PI3K/Akt bias leading to a disinhibition of pyramidal neurons. Ethanol dependence produced opposite IL-1 effects - enhanced local inhibition via a switch in IL-1ß signaling to the canonical pro-inflammatory MyD88 pathway. Ethanol dependence also increased cellular IL-1ß in the mPFC, while decreasing expression of downstream effectors (Akt, p38 MAPK). Thus, IL-1ß may represent a key neural substrate in ethanol-induced cortical dysfunction. As the IL-1 receptor antagonist (kineret) is already FDA-approved for other diseases, this work underscores the high therapeutic potential of IL-1 signaling/neuroimmune-based treatments for AUD.

Implementation of the accelerated care of torsion pathway: a quality improvement initiative for testicular torsion.

BACKGROUND: Timely diagnosis and management of testicular torsion is of paramount importance. Furthermore, time to surgical intervention is a benchmark for the quality of care provided by pediatric urologists included in US News and World Report (USNWR) methodology. OBJECTIVE: We sought to optimize management of acute testicular torsion at a single institution by decreasing time from presentation to definitive management through the creation and implementation of a clinical care pathway (accelerated care of torsion or ACT) for acute testicular torsion in a 2-year period. STUDY DESIGN: Multidisciplinary process mapping involving the emergency department (ED), radiology, anesthesiology, peri-operative services, and operating room (OR) teams resulted in development of the ACT pathway with the goal of achieving surgical intervention within 4 h of arrival at our institution. The accelerated care of torsion pathway was implemented in April 2016. Thirty-eight consecutive acute torsion cases were then prospectively evaluated from April 2016 to April 2018. For process measures, we recorded triage to OR times and mode of presentation. For outcome measures, we examined orchiectomy rates. We retrospectively reviewed 97 cases of acute torsion from 2004 to 2016 as a control. RESULTS: Time from ED triage to OR start decreased from a median 196 min (interquartile range [IQR] 137-249 min) to 127 min (IQR 100-148 min; P < 0.0001) for all cases of acute torsion. In the control group, 72% of cases met the USNWR criteria for acute treatment of torsion. After ACT implementation, 100% of cases reached the OR within the 240 min time frame. Orchiectomy rates were performed in 24% of control cases vs 30% after ACT implementation (P = NS). Survival curve analysis demonstrated no significant difference in probability of testis salvage before or after implementation of the ACT pathway. DISCUSSION: In agreement with similar studies, despite a significant reduction in triage to OR times, the orchiectomy rate approached 30%. This outcome did not significantly improve after implementation of the ACT pathway. Overall ischemia time was a more important determinant of testis salvage. Study limitations include limited patient follow-up to assess testis atrophy. CONCLUSIONS: The multidisciplinary creation and implementation of a clinical pathway for the care of acute testis torsion has significantly decreased the time from ED to OR in our institution. However, overall orchiectomy rate was not significantly affected.

Robotic excision and ureteroureterostomy of blind-ending ureteral 'Duplication'.

INTRODUCTION: Duplicated ureteral anatomy can be a reconstructive challenge. Blind-ending ureteral duplication has been reported with recommendations for surgical excision. OBJECTIVE: This video reviews the importance of exposure of anatomic landmarks in surgical excision of a blind-ending ureteral duplication. MATERIALS AND METHODS: This is a retrospective case report of a patient who presented with a blind-ending ureteral duplication. DISCUSSION: A 13-year-old female presented with a right-sided abdominal mass. Abdominal and pelvic imaging revealed a tubular structure adjacent to and below the right kidney, possibly connecting to the right lower pole. While initially observed, the patient re-presented with urosepsis. A retrograde pyelogram showed no connection between the right ureter and this structure. The patient underwent robotic-assisted excision of this structure. Intra-operatively, it was connected to the right lower pole calyces. A ureteroureterostomy to the orthotopic ureter was performed. Although the structure was adjacent to the bladder dome, there was no communication distally. Postoperatively, the patient did well; follow-up imaging showed a non-dilated lower pole. The pathology of this structure was benign urothelium. CONCLUSIONS: Surgical management of aberrant ureteral duplications should focus on identifying known landmarks and should be considered to prevent symptomatic infections and renal scarring.

Reoperative robotic pyeloplasty in children.

INTRODUCTION: Reoperative pyeloplasty for recurrent ureteropelvic junction obstruction (UPJO) can be technically challenging and is associated with greater morbidity and lower success rates than an initial repair. Robotic-assisted laparoscopic pyeloplasty (RALP) previously has been demonstrated to be a safe and effective approach for management of recurrent UPJO; however, the length of follow-up has been limited. The objective of this study was to confirm the safety and efficacy of RALP for UPJO in children following failed previous pyeloplasty and provide clinical benchmarks for intermediate length follow-up in this patient population. METHODS: An IRB approved retrospective chart review was performed for all patients undergoing reoperative RALP from June 2006 to December 2014. All cases were performed by surgeons from two institutions for persistent UPJO following failed initial pyeloplasty. Information including demographic information, radiographic studies, and operative interventions performed between the initial repair and reoperative surgery, reoperative RALP intraoperative data, postoperative clinical course and imaging studies, and subsequent interventions following reoperative RALP were extracted. RESULTS: Twenty-three children underwent reoperative RALP. Eleven patients had right- and 12 left-sided repairs. Median age at reoperative RALP was 4.0 years and median interval between surgeries was 1.3 years. Indications for repeat repair included pain, infection, and/or radiographic evidence of worsening obstruction and/or deteriorating renal function. Mean operative time was 198 min from incision to port closure. Mean length of stay was 2.3 days. Six complications occurred in five patients within 30 days postoperatively, including ileus, pneumonia, and urinary tract infection. Median length of follow-up was 26 months (range 4-45 months) for all patients and 31 months (range 16-45 months) in 18 patients with >12 months of follow-up. More than 80% of patients presenting with flank pain prior to reoperative RALP had resolution of this symptom. To date, 78% of patients with >12 months of follow-up have not required further operative intervention. Excellent results have been achieved in 14 of 18 patients (78%) with sufficient postoperative follow-up in terms of length of follow-up (>12 months), symptom resolution, and/or improved imaging results. CONCLUSIONS: RALP following previous pyeloplasty is technically feasible with acceptable operative times, lengths of stay, and complication rates. Reoperative RALP is our preferred modality for repair of recurrent UPJO with the vast majority of patients having successful outcomes based on imaging, resolution of symptoms, and the rare need for further intervention across an intermediate length follow-up period.

Promotion ofin vitro shoot formation from excised roots of silktree (Albizzia julibrissin) by an oxime ether derivative and other ethylene inhibitors.

This report describes the regeneration response of excised seedling roots of silktree (Albizzia julibrissin) to added ethylene precursors/generators (1-amino-cyclopropane-1-carboxylic acid [ACC], 2-chloroethylphosphonic acid [CEPA]), biosynthesis inhibitors (aminoethoxyvinylglycine [AVG], an oxime ether derivative [OED={[(ispropylidene)-amino]oxy}-acetic acid-2-(methoxy)-2-oxoethyl ester], CoCl(2) [Co(++)]), and an ethylene action inhibitor (AgNO3 [Ag(+)]). When placed on B5 medium, about 50% of the control explants formed shoot buds within 15 days. Addition of ACC or CEPA (1-10 µM) to the culture medium decreased both the percentage of cultures forming shoots and the number of shoots formed per culture. In contrast, AVG and OED (1-10 µM) increased shoot formation to almost 100% and increased the number of shoots formed per culture. Likewise, both Co(++) and Ag(+) (1-10 µM) increased shoot regeneration, but the number of shoots produced after 30 days was less than with AVG or OED. The inhibitors of ethylene biosynthesis were partially effective in counteracting the inhibitory effect of ACC on shoot formation. These results suggest that modulation of ethylene biosynthesis and/or action can strongly influence the formation of adventitious shoots from excised roots of silktree.