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Objective: To determine the feasibility and safety of performing robotic-assisted laparoscopic urological surgery (RALS) in infants and young children, highlighting technical challenges posed by the smaller body size and their potential solutions., Patients and Methods: We retrospectively reviewed perioperative records of all patients less than 3 years of age who underwent RALS at our institution between January 2006 and October 2012. Intraoperative data included difficulties with the robotic instruments or surgical procedure. Post-operative data included length of hospital stay and any complications., Results: A total of 65 children less than 3 years underwent RALS. The average patient age was 1.6 years ± 0.7, with 14 patients under 1 year of age. Median patient weight was 11.6 kg ± 2.5 kg. Mean operative time was 153.3 ± 57 min. No conversions to open technique or intra-operative complications were reported. A total of 12 post-operative complications were identified after a mean follow-up of 13.6 months: 7 early complications and 5 late complications. Smaller children did not have more complications than larger children., Conclusion: There are inherent challenges with performing RALS in infants and young children. However, they may be overcome with specific technical maneuvers and through understanding of the limitations of the robotic system., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to compare the feasibility of closed-loop anesthesia delivery with manual control of propofol in pediatric patients during cardiac surgery., Methods: Forty ASA II-III children, undergoing elective cardiac surgery under cardiopulmonary bypass (CPB) in a tertiary care hospital, were randomized to receive propofol either through a closed-loop anesthesia delivery system (CL group) or through traditional manual control (manual group) to achieve a target BIS of 50. Patients were induced and subsequently maintained with a propofol infusion. The propofol usage and the efficacy of closed-loop system in controlling BIS within ±10 of the target were compared with that of manual control., Results: The maintenance of BIS within ±10 of target and intraoperative hemodynamic stability were similar between the two groups. However, induction dose of propofol was less in the CL group (2.06 ± 0.79 mg·kg(-1) ) than the manual group (2.95 ± 1.03 mg·kg(-1) ) (P = 0.006) with less overshoot of BIS during induction in the closed-loop group (P = 0.007). Total propofol used in the off-CPB period was less in the CL group (6.29 ± 2.48 mg·kg(-1) h(-1) vs 7.82 ± 2.1 mg·kg(-1) h(-1) ) (P = 0.037). Phenylephrine use in the pre-CPB period was more in the manual group (16.92 ± 10.92 μg·kg(-1) vs 5.79 ± 5.98 μg·kg(-1) ) (P = 0.014). Manual group required a median of 18 (range 8-29) dose adjustments per hour, while the CL group required none., Conclusion: This study demonstrated the feasibility of closed-loop controlled propofol anesthesia in children, even in challenging procedures such as cardiac surgery. Closed-loop system needs further and larger evaluation to establish its safety and efficacy., (© 2013 John Wiley & Sons Ltd.)

Current cocaine treatments may be enhanced with a better understanding of the underlying mechanisms that contribute to the onset and maintenance of the disease, such as life stress and impulsivity. Life stress and impulsivity have previously been studied independently as contributors to drug use, and the current study expands upon past research by examining how these factors interact with one another. The aim of the current study was to evaluate the role of life stress in predicting impulsivity in a non-treatment seeking cocaine-dependent sample (N=112). Analyses revealed that trait impulsivity (as measured by the Barratt Impulsiveness Scale) was associated with education (r=-3.09, p<0.01), as those who had higher educational attainment also reported lower rates of trait impulsivity. In addition, those over the age of 30 demonstrated lower impulsivity in decision-making (as measured by delay discounting) than those under 30 (t=2.21, p=0.03). Overall exposure to life stress was not significantly correlated to either aspect of impulsivity. However several specific life stressors were significantly related to greater impulsivity including having been put up for adoption or in foster care (t=-2.96, p<0.01), and having a child taken away against their will (t=-2.68, p=0.01). These findings suggest that age and education relate to impulsivity; and that while an overall compilation of life stress scores was not related to impulsivity, specific types of stress related to either being taken away from a parent or having a child taken away were. Future studies should assess these constructs longitudinally to restrict response bias., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Phenylketonuria (PKU) is a well-defined metabolic disorder arising from a mutation that disrupts phenylalanine metabolism and so produces a variety of neural changes indirectly. Severe cognitive impairment can be prevented by dietary treatment; however, residual symptoms may be reported. These residual symptoms appear to overlap a more prevalent childhood disorder: Attention Deficit/Hyperactivity Disorder (ADHD). However, the aetiology of ADHD is a vast contrast to PKU: it seems to arise from a complex combination of genes; and it has a substantial environmental component. We ask whether these two disorders result from two vastly different genotypes that converge on a specific core phenotype that includes similar dysfunctions of Gray's (Gray, 1982) Behavioural Inhibition System (BIS), coupled with other disorder-specific dysfunctions. If so, we believe comparison of the commonalities will allow greater understanding of the neuropsychology of both disorders. We review in detail the aetiology, treatment, neural pathology, cognitive deficits and electrophysiological abnormalities of PKU; and compare this with selected directly matching aspects of ADHD. The biochemical and neural pathologies of PKU and ADHD are quite distinct in their causes and detail; but they result in the disorder in the brain of large amino acid levels, dopamine and white matter that are very similar and could explain the overlap of symptoms within and between the PKU and ADHD spectra. The common deficits affect visual function, motor function, attention, working memory, planning, and inhibition. For each of PKU and ADHD separately, a subset of deficits has been attributed to a primary dysfunction of behavioural inhibition. In the case of ADHD (excluding the inattentive subtype) this has been proposed to involve a specific failure of the BIS; and we suggest that this is also true of PKU. This accounts for a substantial proportion of the parallels in the superficial symptoms of both disorders and we see this as linked to prefrontal, rather than more general, dysfunction of the BIS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: This study was designed to evaluate multimodal prognostication in patients after cardiac arrest (CA)., Background: Accurate methods to predict outcome after CA are lacking., Methods: Seventy-five patients with CA treated with therapeutic hypothermia after cardiac resuscitation were enrolled in this prospective observational study. Serum levels of neuron-specific enolase (NSE) and neuron-enriched S100 beta (S100β) were measured 48 h after CA. Bispectral index (BIS) was continuously monitored during the first 48 h after CA. The primary endpoint was neurological outcome, as defined by the cerebral performance category (CPC) at 6-month follow-up: scores 1 or 2 indicated good outcome, and scores 3 to 5, poor outcome. The secondary endpoint was survival., Results: A total of 46 (61%) patients survived at 6 months and 41 (55%) patients had CPC 1 or 2. Levels of NSE and S100β were higher in patients with poor outcomes compared with patients with good outcomes (4-fold and 10-fold, respectively; p < 0.001). BIS was lower in patients with poor outcomes (10-fold; p < 0.001). NSE, S100β, or BIS alone predicted neurological outcome, with areas under the receiver-operating characteristic curve (AUC) above 0.80. Combined determination of S100β and BIS had an incremental predictive value (AUC: 0.95). S100β improved discriminations based on BIS (p = 0.0008), and BIS improved discriminations based on S100β (p < 10(-5)). Patients with S100β level above 0.03 μg/l and BIS below 5.5 had a 3.6-fold higher risk of poor neurological outcome (p < 0.0001). S100β and BIS predicted 6-month mortality (log-rank statistic: 50.41; p < 0.001)., Conclusions: Combined determination of serum level of S100β and BIS monitoring accurately predicts outcome after CA., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This study investigates the effects of a restricted diet (RD) on body composition and musculoskeletal health along with endocrines and molecular mechanism in established mature obese rats. Twenty female rats were fed with a high-fat diet (HFD) ad libitum for 4 months and then assigned to either HFD or RD group for another 4 months. Another 10 rats were on a low-fat diet for 8 months. Outcome measures included body composition, bone mineral density, microarchitecrure, and strength; serum leptin, adiponectin, insulin-like growth factor I, and liver glutathione peroxidase activity; and protein expression and spleen tumor necrosis factor α messenger RNA expression. We hypothesized that mature obese rats on a 35% energy restriction diet for 4 months would improve body composition but degrade microstructural and mechanical properties of long bones, and such changes in musculoskeletal integrity are related to the modulation of obesity-related endocrines and proinflammation. Relative to HFD, RD benefited body composition (decreased body weight and %fat mass and increased %fat-free mass); decreased insulin-like growth factor I and leptin; elevated adiponectin, glutathione peroxidase activity and protein expression and tumor necrosis factor α messenger RNA expression; and suppressed bone formation and increased bone resorption, resulting in decreased trabecular and cortical bone volume, bone mineral density, and bone strength. Relative to low-fat diet, RD had a similar effect on body composition and serum markers but increased bone turnover rate and decreased bone mineral density and strength. Our data suggest that long-term RD has a negative impact on bone remodeling in obese female rats, probably through modification of endocrines and elevation of proinflammation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In the heart, Na/K-ATPase regulates intracellular Na(+) and Ca(2+) (via NCX), thereby preventing Na(+) and Ca(2+) overload and arrhythmias. Here, we test the hypothesis that nitric oxide (NO) regulates cardiac intracellular Na(+) and Ca(2+) and investigate mechanisms and physiological consequences involved. Effects of both exogenous NO (via NO-donors) and endogenously synthesized NO (via field-stimulation of ventricular myocytes) were assessed in this study. Field stimulation of rat ventricular myocytes significantly increased endogenous NO (18 ± 2 μM), PKCε activation (82 ± 12%), phospholemman phosphorylation (at Ser-63 and Ser-68) and Na/K-ATPase activity (measured by DAF-FM dye, western-blotting and biochemical assay, respectively; p<0.05, n=6) and all were abolished by Ca(2+)-chelation (EGTA 10mM) or NOS inhibition l-NAME (1mM). Exogenously added NO (spermine-NONO-ate) stimulated Na/K-ATPase (EC50=3.8 μM; n=6/grp), via decrease in Km, in PLM(WT) but not PLM(KO) or PLM(3SA) myocytes (where phospholemman cannot be phosphorylated) as measured by whole-cell perforated-patch clamp. Field-stimulation with l-NAME or PKC-inhibitor (2 μM Bis) resulted in elevated intracellular Na(+) (22 ± 1.5 and 24 ± 2 respectively, vs. 14 ± 0.6mM in controls) in SBFI-AM-loaded rat myocytes. Arrhythmia incidence was significantly increased in rat hearts paced in the presence of l-NAME (and this was reversed by l-arginine), as well as in PLM(3SA) mouse hearts but not PLM(WT) and PLM(KO). We provide physiological and biochemical evidence for a novel regulatory pathway whereby NO activates Na/K-ATPase via phospholemman phosphorylation and thereby limits Na(+) and Ca(2+) overload and arrhythmias. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes"., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Approach and avoidance motivation may represent important explanatory constructs in understanding how individuals differ. Such constructs have primarily been assessed in self-reported terms, but there are limitations to self-reports of motivation. Accordingly, the present review concentrates on the potential utility of implicit cognitive-behavioral probes of approach and avoidance motivation in modeling and understanding individual differences. The review summarizes multiple lines of research that have documented the utility of such probes to the personality-processing interface. Although multiple gaps to our knowledge exist, and are acknowledged, the value of such implicit cognitive-behavioral assessments is emphasized both in modeling multiple sub-components of approach and avoidance motivation and in showing that such tendencies matter in ways that transcend momentary experiences or manipulations.

Background: Budesonide inhalation suspension (BIS) and montelukast provide acceptable asthma control, whereas overall measures favored BIS in children aged 2 to 8 years with mild persistent asthma., Objective: We compared BIS and montelukast over a 1-year period in children aged 2 to 4 years with asthma., Methods: Data were derived from a 52-week, open-label, randomized, active-controlled, multicenter study (NCT00641472). Children with mild asthma received either BIS 0.5 mg or montelukast 4 to 5 mg once daily. Patients were stepped up to twice-daily BIS or oral corticosteroids for mild or severe asthma worsening, respectively. Primary efficacy assessment was time to first additional asthma medication for exacerbation over 52 weeks., Results: Two hundred two patients, age 2 to 4 years, received BIS (n = 105) or montelukast (n = 97). No difference was observed between the BIS and montelukast groups in median time to first additional asthma medication over 52 weeks (183 vs 86 days). Statistically significant differences were observed in favor of BIS over montelukast in the percentage of patients requiring oral steroids at 52 weeks (21.9% vs 37.1%; P = .022), the rate (number/patient/year) of additional courses of medication (1.35 vs 2.30; P = .003), the rate of additional oral steroid therapy (0.44 vs 0.88; P = .008), and caregivers' ability to manage the patient's symptoms (P = .026). Both treatments were well tolerated., Conclusion: BIS and montelukast provided acceptable asthma control in children aged 2 to 4 years with mild persistent asthma with no significant difference between treatments in the primary end point; however, several secondary outcomes showed statistically significant differences (and many had numerical differences) in favor of BIS over montelukast., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: This prospective, randomized, double blinded, controlled study was designed to compare effects of intravenous co-administration of clonidine, magnesium, or ketamine on anesthetic consumption, intraoperative hemodynamics, postoperative analgesia and recovery indices during Bispectral Index (BIS) guided total intravenous anesthesia (TIVA)., Methods: After ethical committee approval and written informed consent, 120 adult patients ASA I and II scheduled for open cholecystectomy were randomly assigned to one of 4 equal groups. Group CL received clonidine 3 µg/kg and maintained by 2 µg/kg/h. Group MG received magnesium sulphate 50 mg/kg and maintained by 8 mg/kg/h. Group KET received racemic ketamine 0.4 mg/kg and maintained by 0.2 mg/kg/h. Control group (CT) received the same volume of isotonic saline. Anesthesia was induced and maintained by fentanyl, propofol and rocuronium. Propofol infusion was adjusted to keep the BIS value between 45-55. Intraoperative hemodynamics, induction time, anesthetic consumption, recovery indices, and PACU discharge were recorded., Results: Induction time, propofol requirements for induction and maintenance of anesthesia, intraoperative fentanyl and hemodynamic values were significantly lower with Groups CL and MG compared to Groups KET and CT (P < 0.05). Patients in Group MG showed significantly lower muscle relaxant consumption, delayed recovery and PACU discharge than other groups (P < 0.05). First, analgesic requirement was significantly longer and total postoperative analgesic consumption was significantly lower in the adjuvant groups versus Group CT (P < 0.05)., Conclusions: Clonidine, magnesium, and ketamine can be useful adjuvant agents to BIS-guided TIVA. Pharmacokinetic studies of such drug combinations were recommended to investigate their interaction.

Accumulating evidence suggests that individual differences in punishment and reward sensitivity are associated with functional alterations in neural systems underlying error and feedback processing. In particular, individuals highly sensitive to punishment have been found to be characterized by larger mediofrontal error signals as reflected in the error negativity/error-related negativity (Ne/ERN) and the feedback-related negativity (FRN). By contrast, reward sensitivity has been shown to relate to the error positivity (Pe). Given that Ne/ERN, FRN, and Pe have been functionally linked to flexible behavioral adaptation, the aim of the present research was to examine how these electrophysiological reflections of error and feedback processing vary as a function of punishment and reward sensitivity during reinforcement learning. We applied a probabilistic learning task that involved three different conditions of feedback validity (100%, 80%, and 50%). In contrast to prior studies using response competition tasks, we did not find reliable correlations between punishment sensitivity and the Ne/ERN. Instead, higher punishment sensitivity predicted larger FRN amplitudes, irrespective of feedback validity. Moreover, higher reward sensitivity was associated with a larger Pe. However, only reward sensitivity was related to better overall learning performance and higher post-error accuracy, whereas highly punishment sensitive participants showed impaired learning performance, suggesting that larger negative feedback-related error signals were not beneficial for learning or even reflected maladaptive information processing in these individuals. Thus, although our findings indicate that individual differences in reward and punishment sensitivity are related to electrophysiological correlates of error and feedback processing, we found less evidence for influences of these personality characteristics on the relation between performance monitoring and feedback-based learning.

Social power, alcohol intoxication, and anonymity all have strong influences on human cognition and behavior. However, the social consequences of each of these conditions can be diverse, sometimes producing prosocial outcomes and other times enabling antisocial behavior. We present a general model of disinhibition to explain how these seemingly contradictory effects emerge from a single underlying mechanism: The decreased salience of competing response options prevents activation of the Behavioral Inhibition System (BIS). As a result, the most salient response in any given situation is expressed, regardless of whether it has prosocial or antisocial consequences. We review three distinct routes through which power, alcohol intoxication, and anonymity reduce the salience of competing response options, namely, through Behavioral Approach System (BAS) activation, cognitive depletion, and reduced social desirability concerns. We further discuss how these states can both reveal and shape the person. Overall, our approach allows for multiple domain-specific models to be unified within a common conceptual framework that explains how both situational and dispositional factors can influence the expression of disinhibited behavior, producing both prosocial and antisocial outcomes., (© Association for Psychological Science 2011.)

Background: Induction of anesthesia is the most crucial period of general anesthesia. Inhalational induction is the most commonly used technique in pediatric anesthesia. Tracheal intubation can be done after reaching the deep levels of anesthesia. The depth of anesthesia is often difficult to be judged. Bispectral index is a measure of the effects of anesthesia on brain. This study was designed to evaluate the efficacy of bispectral index (BIS) in clarifying suitable depth of anesthesia for tracheal intubation during inhalational induction of anesthesia., Methods: In a clinical trial, ninety patients, ASA I & II, 1 to 6 years old, scheduled for elective surgery were enrolled into the study. After starting BIS monitoring, patients randomly were divided into three groups. Then, anesthesia was induced by gradual increase of halothane in 50% mixture of oxygen (O(2)) and N(2)O and continued until target BIS (60 ± 2, 50 ± 2 and 40 ± 2) achieved. After tracheal intubation, the duration of laryngoscopy and the presence of laryngospasm, bronchospasm, laryngoscopy failure, the movement of extremities and the changes in SpO2 and BIS were recorded. The data were analyzed by chi-square and ANOVA at 0.05 level of significance., Results: BIS could not determine the appropriate level of anesthesia for tracheal intubation in this setting. There were no differences in laryngoscopy duration and the occurrence of laryngospasm, bronchospasm, laryngoscopy failure, extremity movement and awakening time among three groups., Conclusions: These results confirmed that there was no significant difference in the incidence of complications related to intubation at different BIS values (from 60 to 40) during inhalation induction, and probably to achieve an adequate or more reliable depth of anesthesia, the lower values of BIS is required.

Background: Theoretically, L-type calcium channel blockers could modulate anesthetic effects. Nicardipine does not affect the bispectral index (BIS), but nimodipine, which can penetrate the blood-brain barrier, has not been studied. The aim of this study was to evaluate whether a single dose of intravenous nicardipine or nimodipine could affect BIS following rapid sequence intubation., Methods: This study was done in a double-blind, randomized fashion. Anesthesia was induced with fentanyl 2 µg/kg, thiopental sodium 5 mg/kg, and 100% oxygen. After loss of consciousness, patients received rocuronium 1.0 mg/kg and either a bolus of 20 µg/kg nicardipine, nimodipine, or a comparable volume of normal saline (n = 20). Intubation was performed 1 min after study drug administration. BIS, mean blood pressure (MBP), and heart rate (HR) were measured before anesthetic induction, after loss of consciousness, before intubation, during intubation, and 1, 2 and 5 min after intubation., Results: BIS dropped rapidly after induction but increased to 60 before intubation in all groups irrespective of study drug. In nimodipine, the increase in BIS during intubation was not significant compared to pre-intubation, in contrast to the other two groups, but there was no difference in BIS during intubation. HR significantly increased, but MBP just rose to pre-induction values after intubation in nicardipine and nimodipine groups. BIS, MBP, and HR following intubation increased in control group., Conclusions: A single dose of intravenous nicardipine or nimodipine could attenuate blood pressure increases but not affect BIS increases in rapid sequence intubation.

Background and objective Perioperative low-dose ketamine has been useful for postoperative analgesia. In this study we wanted to assess the analgesic effect and possible side-effects of perioperative low-dose S (+) ketamine when added to a regime of non-opioid multimodal pain prophylaxis. Methods Seventy-seven patients scheduled for haemorrhoidectomy were enrolled in this randomized, double-blind, controlled study. They received oral paracetamol 1-2 g, total intravenous anaesthesia, intravenous 8 mg dexamethasone, 30 mg ketorolac and local infiltration with bupivacaine/epinephrine. Patients randomized to S (+) ketamine received an intravenous bolus dose of 0.35 mg kg-1 S (+) ketamine before start of surgery followed by continuous infusion of 5 μg kg-1 min-1 until 2 min after end of surgery. Patients in the placebo group got isotonic saline (bolus and infusion). BISTM monitoring was used. Pain intensity and side-effects were assessed by blinded nursing staff during PACU stay and by phone 1, 7 and 90 days after surgery. Results In patients randomized to S (+) ketamine emergence from anaesthesia was significantly longer (13.1 min vs. 9.3 min; p < 0.001). BIS values were significantly higher during anaesthesia (maximal value during surgery: 62 vs. 57; p = 0.01) and when opening eyes (81 vs. 70, p < 0.001). Pain scores (NRS and VAS) did not differ significantly between groups. Conclusions The addition of perioperative S (+) ketamine for postoperative analgesia after haemorrhoidectomy on top of multimodal non-opioid pain prophylaxis does not seem to be warranted, due to delayed emergence and recovery, more side-effects, altered BIS readings and absence of additive analgesic effect.

Summary: Regional anaesthesia has become an important anaesthetic technique. Effective sedation is an essential for regional techniques too. This study compares midazolam and propofol in terms of onset & recovery from sedation, dosage and side effects of both the drugs using Bispectral Index monitoring. Ninety eight patients were randomly divided into two groups,one group recieved midazolam infusion while the other recieved propofol infusion until BIS reached 75. We observed Time to reach desired sedation, HR, MABP, time for recovery, dose to reach sedation and for maintenance of sedation and side effects if any. The time to reach required sedation was 11 min in Midazolam group(Group I) while it was 6 min in Propofol group(Group II) (p=0.0). Fall in MABP was greater with propofol. Recovery in with midazolam was slower than with propofol (18.6 +/- 6.5 vs 10.10+/-3.65 min) (p=0.00). We concluded that both midazolam and propofol are effective sedatives, but onset and offset was quicker with propofol, while midazolam was more cardiostable.

Previous observations suggest that Bis, a Bcl-2-binding protein, may play a role the neuronal and glial differentiation in vivo. To examine this further, we investigated Bis expression during the in vitro differentiation of P19 embryonic carcinoma cells induced by retinoic acid (RA). Western blotting and RT-PCR assays showed that Bis expression was temporarily decreased during the free floating stage and then began to increase on day 6 after the induction of differentiation. Double immunostaining indicated that Bis-expressing cells do not express several markers of differentiation, including NeuN, MAP-2 and Tuj-1. However, some of the Bis-expressing cells also were stained with GFAP-antibodies, indicating that Bis is involved glial differentiation. Using an shRNA strategy, we developed bis-knock down P19 cells and compared them with control P19 cells for the expression of NeuroD, Mash-1 and GFAP during RA-induced differentiation. Among these, only GFAP induction was significantly attenuated in P19-dnbis cells and the population showing GFAP immunoreactivity was also decreased. It is noteworthy that distribution of mature neurons and migrating neurons was disorganized, and the close association of migrating neuroblasts with astrocytes was not observed in P19-dnbis cells. These results suggest that Bis is involved in the migration-inducing activity of glial cells.