Epidural Analgesia Decreases Narcotic Requirements in Low Level Spina Bifida Patients Undergoing Urologic Laparotomy for Neurogenic Bladder and Bowel

Purpose Concern of anatomical anomalies and worsening neurologic symptoms has prevented widespread use of epidural catheters in patients with low level spina bifida (LLSB). We hypothesize that thoracic epidural placement in the T9-T10 interspace is safe and decreases narcotic requirements in LLSB patients following major open lower urinary tract reconstruction (LUTR). Materials and Methods We reviewed consecutive LLSB patients who had LUTR and epidurals for post-operative pain control. Controls were LLSB patients who received single shot transversus abdominis plane (TAP) blocks with similar procedures. Complications from epidural placement, including changes in motor and sensory status were recorded. Opioid consumption was calculated utilizing equivalent IV morphine doses. Mean and maximum pain scores on post-operative day (POD) 0-3 were calculated. Results 10 LLSB patients who had lower urinary tract reconstruction and epidurals were matched to 10 LLSB patients who had lower urinary tract reconstruction and transverse abdominis plane blocks. Groups were demographically similar. All had full abdominal sensation and functional levels at or below L3. No epidural complications or changes in neurological status were noted. The epidural group had decreased opioid consumption on POD 0-3 (0.75 mg/kg vs. 1.29 mg/kg, p=0.04). Pain scores were similar or improved in the epidural group. Conclusions Thoracic epidural analgesia appears to be a safe and effective opioid sparing option to assist with post-operative pain management following lower urinary tract reconstruction in LLSB patients

Transitioning Young Adults with Neurogenic Bladder – Are We Asking Too Much?

Introduction Significant numbers of young adults with chronic health conditions fail to transition. Objective We aimed to evaluate how ready urologic patients who have transitioned were actually prepared for that process. Due to the cognitive impairments frequently seen with spina bifida (SB), we hypothesize that these individuals will be less prepared to transition medical care to adult providers compared to their healthy counterparts. Methods Participants included consecutive patients in the transitional SB clinic at our institution and controls (college student without obvious physical disability or interest in healthcare related fields aged 18-25). Both groups were administered the Transition Readiness Assessment Questionnaire (TRAQ) over a nine-month period. Five TRAQ domains assess 20 skills necessary to transition. Likert scale responses range from 1 “No, I do not know how” to 5 “Yes, I always do this when I need to” (which we considered appropriate for transitioned patients). Demographics and the number of daily medications taken were collected. Patients and healthy controls were compared using 1) total and domain TRAQ scores, 2) the proportion of non-transitioned skills (“1”) and 3) fully transitioned skills (“5”). Non-parametric statistics were used. Results 43 unique SB patients (30.8% shunted, 46.5% female) and 100 controls were enrolled. SB patients were older than controls (21 vs 20 years, p<0.001). There was no gender difference between groups (p=0.33). Transitioned patients and college students were fully transitioned only in the “Talking with Providers” domain ( Figure ). College students performed significantly better than patients in the domains of “Appointment Keeping” (p=0.04) and “Tracking Health Issues” (p=0.02). Transitioned patients were less likely to be interested in learning how to perform skills in the domains of “Appointment Keeping” and “Tracking Health Issues” (p<0.001 for both domains). Discussion We describe the transition readiness of young adults with SB compared to healthy controls and other youths with chronic health conditions. Limitations include the small sample size, potentially limiting generalizability, as well as cross-sectional nature. Conclusion “Transitioned” patients with SB had lower TRAQ scores in some domains compared to healthy college students, who themselves had scores indicating that they were not fully ready for transition. Increased attention to transition readiness in people with SB is necessary, as even healthy young adults struggle with these tasks and are poorly prepared for transition

The effect of reionization on direct measurements of the mean free path

Recent measurements of the ionizing photon mean free path (MFP) based on composite quasar spectra may point to a late end to reionization at $z<6$. These measurements are challenging, however, because they rely on assumptions about the proximity zones of the quasars in the analysis. For example, some of the $z\sim 6$ quasars in the composite might have been close to large-scale regions where reionization was still ongoing ("neutral islands"), and it is unclear how this would affect the measurements. We address the question here with mock MFP measurements from radiative transfer simulations. We find that, even in the presence of neutral islands, the inferred MFP tracks to within $30 \%$ the true attenuation scale of the spatially averaged IGM, which includes opacity from both the ionized medium and the islands. During reionization, this scale is always shorter than the MFP in the ionized medium. The inferred MFP is sensitive at the $< 50\%$ level to assumptions about the quasar environments and lifetimes for realistic models. We demonstrate that future analyses with improved data may require explicitly modeling the effects of neutral islands on the composite spectra, and we outline a method for doing this. Lastly, we quantify the effects of neutral islands on Lyman-series transmission, which has been modeled with optically thin simulations in previous MFP analyses. Neutral islands can suppress transmission at $\lambda_{\rm rest} < 912$ \r{A} significantly, up to a factor of 2 for $z_{\rm qso} = 6$ in a plausible reionization scenario, owing to absorption by many closely spaced lines as quasar light redshifts into resonance. However, the suppression is almost entirely degenerate with the spectrum normalization, thus does not significantly bias the inferred MFP.Comment: 11 pages, 8 figures, submitted to MNRA

Serotonin receptors and heart valve disease—It was meant 2B

Carcinoid heart disease was one of the first valvular pathologies studied in molecular detail, and early research identified serotonin produced by oncogenic enterochromaffin cells as the likely culprit in causing changes in heart valve tissue. Researchers and physicians in the mid-1960s noted a connection between the use of several ergot-derived medications with structures similar to serotonin and the development of heart valve pathologies similar to those observed in carcinoid patients. The exact serotonergic target that mediated valvular pathogenesis remained a mystery for many years until similar cases were reported in patients using the popular diet drug Fen-Phen in the late 1990s. The Fen-Phen episode sparked renewed interest in serotonin-mediated valve disease, and studies led to the identification of the 5-HT2B receptor as the likely molecular target leading to heart valve tissue fibrosis. Subsequent studies have identified numerous other activators of the 5-HT2B receptor, and consequently, the use of many of these molecules has been linked to heart valve disease. Herein, we: review the molecular properties of the 5-HT2B receptor including factors that differentiate the 5-HT2B receptor from other 5-HT receptor subtypes, discuss the studies that led to the identification of the 5-HT2B receptor as the mediator of heart valve disease, present current efforts to identify potential valvulopathogens by screening for 5-HT2B receptor activity, and speculate on potential therapeutic benefits of 5-HT2B receptor targeting

Characteristics of Female Genital Restoration Surgery for Congenital Adrenal Hyperplasia Using a Large-scale Administrative Database

Objective To analyze nationwide information on the timing of surgical procedures, cost of surgery, hospital length of stay following surgery, and surgical complications of female genital restoration surgery (FGRS) in females with congenital adrenal hyperplasia (CAH). Materials and Methods We used the Pediatric Health Information System database to identify patients with CAH who underwent their initial FGRS in 2004-2014. These patients were identified by an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code for adrenogenital disorders (255.2) in addition to a vaginal ICD-9 procedure code (70.x, excluding vaginoscopy only) or perineal ICD-9 procedure code (71.x), which includes clitoral operations (71.4). Results A total of 544 (11.8%) females underwent FGRS between 2004 and 2014. Median age at initial surgery was 9.9 months (interquartile range 6.8-19.1 months). Ninety-two percent underwent a vaginal procedure, 48% underwent a clitoral procedure, and 85% underwent a perineal procedure (non-clitoral). The mean length of stay was 2.5 days (standard deviation 2.5 days). The mean cost of care was $12,258 (median$9,558). Thirty-day readmission rate was 13.8%. Two percent underwent reoperation before discharge, and 1 (0.2%) was readmitted for a reoperation within 30 days. Four percent had a perioperative surgical complication. Conclusion Overall, 12% of girls with CAH underwent FGRS at one of a national collaborative of freestanding children's hospitals. The majority underwent a vaginoplasty as a part of their initial FGRS for CAH. Clitoroplasty was performed on less than half the patients. Overall, FGRS for CAH is performed at a median age of 10 months and has low 30-day complication and immediate reoperation rates

Spectroscopic Discovery of the Broad-Lined Type Ic Supernova 2010bh Associated with the Low-Redshift GRB 100316D

We present the spectroscopic discovery of a broad-lined Type Ic supernova (SN 2010bh) associated with the nearby long-duration gamma-ray burst (GRB) 100316D. At z = 0.0593, this is the third-nearest GRB-SN. Nightly optical spectra obtained with the Magellan telescopes during the first week after explosion reveal the gradual emergence of very broad spectral features superposed on a blue continuum. The supernova features are typical of broad-lined SNe Ic and are generally consistent with previous supernovae associated with low-redshift GRBs. However, the inferred velocities of SN 2010bh at 21 days after explosion are a factor of ~2 times larger than those of the prototypical SN 1998bw at similar epochs, with v ~ 26,000 km/s, indicating a larger explosion energy or a different ejecta structure. A near-infrared spectrum taken 13.8 days after explosion shows no strong evidence for He I at 1.083 microns, implying that the progenitor was largely stripped of its helium envelope. The host galaxy is of low luminosity (M_R ~ -18.5 mag) and low metallicity (Z < 0.4 Z_solar), similar to the hosts of other low-redshift GRB-SNe.Comment: 6 pages, 4 figures, 1 table, submitted to ApJ Letter

Radiographic abnormalities, bladder interventions, and bladder surgery in the first decade of life in children with spina bifida

Background Spina bifida (SB) patients are at increased risk for hydronephrosis, bladder storage and emptying problems, and renal failure that may require multiple bladder surgeries. Methods We retrospectively reviewed patients born with SB 2005–2009, presenting to our institution within 1 year of birth. Outcomes at 8–11 years old included final renal/bladder ultrasound (RBUS) results, clean intermittent catheterization (CIC) use, anticholinergic use, surgical interventions, and final renal function. We excluded those without follow-up past age 8 and/or no RBUS or fluoroscopic urodynamic images (FUI) within the first year of life. Imaging was independently reviewed by four pediatric urologists blinded to radiologists’ interpretation and initial findings compared with final outcomes. Results Of 98 children, 62 met inclusion criteria (48% male, 76% shunted). Median age at last follow-up was 9.6 years. Upon initial imaging, 74% had hydronephrosis (≥ SFU grade 1), decreasing to 5% at 10 years (p < 0.0001). Initially, 9% had ≥ SFU grade 3 hydronephrosis, decreasing to 2% (p = 0.13). CIC and anticholinergic use increased from 61% and 37% to 87% and 86%, respectively (p = 0.001 and p < 0.0001, respectively). With follow-up, 55% had surgical intervention and 23% had an augmentation. Of children with a serum creatinine/cystatin-C at 8–11 years old, one had confirmed chronic kidney disease (stage 2). Conclusions Despite initial high incidence of hydronephrosis, this was low grade and resolved in the first decade of life. Additionally, the 8–11-year incidence of kidney disease and upper tract changes was low due to aggressive medical management

Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties.

The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Using neuron-specific βarr2-KO mice, we show that the antipsychotic-like effects of a βarr2-biased D2R ligand are driven through both striatal antagonism and cortical agonism of D2R-βarr2 signaling. Furthermore, βarr2-biased D2R agonism enhances firing of cortical fast-spiking interneurons. This enhanced cortical agonism of the biased ligand can be attributed to a lack of G-protein signaling and elevated expression of βarr2 and G protein-coupled receptor (GPCR) kinase 2 in the cortex versus the striatum. Therefore, we propose that βarr2-biased D2R ligands that exert region-selective actions could provide a path to develop more effective antipsychotic therapies

Inhibition of Mediodorsal Thalamus Disrupts Thalamofrontal Connectivity and Cognition

Cognitive deficits are central to schizophrenia but the underlying mechanisms still remain unclear. Imaging studies performed in patients point to decreased activity in the medio-dorsal thalamus (MD) and reduced functional connectivity between the MD and prefrontal cortex (PFC) as candidate mechanisms. However, a causal link is still missing. We used a pharmacogenetic approach in mice to diminish MD neuron activity and examined the behavioral and physiological consequences. We found that a subtle decrease in MD activity is sufficient to trigger selective impairments in prefrontal-dependent cognitive tasks. In vivo recordings in behaving animals revealed that MD-PFC beta-range synchrony is enhanced during acquisition and performance of a working memory task. Decreasing MD activity interfered with this task-dependent modulation of MD-PFC synchrony, which correlated with impaired working memory. These findings suggest that altered MD activity is sufficient to disrupt prefrontal-dependent cognitive behaviors, and could contribute to the cognitive symptoms observed in schizophrenia