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Effects of positive GABA(A) modulators on a multiple-component, repeated-acquisition test of spatial learning.

The purpose of this study was to determine the effects of the benzodiazepines, midazolam and chlordiazepoxide, and the barbiturate, pentobarbital, on spatial learning, in a within-subject, repeated-acquisition and performance procedure adapted to the Morris Swim Task. In the presence of one stimulus arrangement, rats learned to swim to a hidden escape platform that was always in the same location in a swimming pool (performance component). In the presence of a second stimulus arrangement, the platform moved to a different place in the pool for each daily session (acquisition component). All subjects completed six training trials in both components during each daily training session, alternating between the two components within each session. Relatively direct paths to the platform and short escape latencies in the performance component, and steep within-session learning curves in the acquisition component, demonstrated that behavior under each component was controlled by the discriminative stimuli. All three GABA(A) modulators increased swim distances, escape latencies, and slowed swim speed in a dose-dependent manner. Midazolam and chlordiazepoxide, but not pentobarbital, produced selective impairments of swim distances and escape latencies in the acquisition component. Benzodiazepines disrupted acquisition at doses that did not disrupt steady-state performance. Pentobarbital impaired acquisition only at doses that also disrupted behavior during the performance component and reduced swimming speeds.

Animals↗

Striatal grafts in infarct striatopallidum increase GABA release, reorganize GABAA receptor and improve water-maze learning in the rat.

We grafted fetal striatal cells in ischemic rat models, and investigated graft survival/growth, GABA release, GABAA receptor reorganization and functional recovery. One hour intraluminal occlusion of the middle cerebral artery (MCA) induced ischemic infarct in the lateral part of the striatum and adjacent cortex. In ischemic rats, the acquisition of Morris' water-maze learning was significantly slower than that of control rats. In these animals GABA level in the globus pallidus, detected by microdialysis, was about the half of that of controls. However, after the grafts of fetal striatal cells in the striatopallidum, the acquisition was improved, thus no difference was observed in the time course of learning curves in control and grafted animals. GABA level recovered to almost normal level by the graft. It further increased by the treatment of a GABA uptake blocker (nipecotic acids) in the perfusion. In the grafts, GABAA receptor organization detected by autoradiography using [3H] labeled SR95531 was restored for more than 1 year after the graft. Data suggest that fetal striatal cell grafts in infarct striatum may partially reconstruct striatopallidal GABA projection and reorganize GABAA receptor. This might be a basis of improvement of function.

Animals↗

Responding changes systematically within sessions during conditioning procedures.

When the procedure is held constant within an experimental session, responding often changes systematically within that session. Many of these within-session changes in responding cannot be dismissed as learning curves or by-products of satiation. They have been observed in studies of positive reinforcement, avoidance, punishment, extinction, discrimination, delayed matching to sample, concept formation, maze and alley running, and laboratory analogues of foraging, as well as in the unconditioned substrates of conditioned behavior. When aversive stimuli are used, responding usually increases early in the session. When positive reinforcers are used, responding changes in a variety of ways, including increasing, decreasing, and bitonic functions. Both strong and minimal reinforcement procedures produce within-session decreases in positively reinforced behavior. Within-session changes in responding have substantial theoretical and methodological implications for research in conditioning.

Animals↗

Telementoring facilitates independent hand-assisted laparoscopic living donor nephrectomy.

Laparoscopic living donor nephrectomy is a major advance but a challenging procedure to learn even after laparoscopic training. It requires significant previous training in both laparoscopic and transplant surgery. Telementoring has been shown to reduce the laparoscopic learning curve in other fields. Of six cases of hand-assisted laparoscopic (HAL) living donor nephrectomy at our institution, an on-site mentor supervised the initial two. We present the subsequent four cases as the first documented examples of telementored HAL live donor nephrectomy. Telelink was established with a Comstation (Zydacron, UK) incorporating a Z360 telementoring codec and four ISDN lines (512 kb/s) with time delay of 500 ms for both audio and video. The remote surgeon in Minnesota (USA) could change independently between the laparoscopic and external views. The operating surgeons were able to look at the mentor and converse with him throughout. There were no adverse events in recipients and graft function was excellent. With regards to the telementored group the mean operative time was 240 minutes, the mean warm ischemic time 189 seconds, the mean estimated blood loss 171 mL, and the mean length of hospital stay 3 days. Telementoring for laparoscopic donor nephrectomy is feasible, effective, and likely to aid independent practice by providing continued supervision and reducing the learning period.

Adult↗

Learning laparoscopic-assisted hysterectomy.

OBJECTIVE: The aim of this study was to evaluate the factors considered for proficiency and to estimate the number of procedures needed to achieve competence in laparoscopic-assisted vaginal hysterectomy in a teaching hospital. METHODS: The length of the learning curve, duration of surgery, change of hemoglobin (in grams per liter), conversion rate, and intra- and postoperative complications were evaluated. Cases were analyzed according to the order for the individual surgeon. RESULTS: Thirty-three surgeons performed 929 laparoscopic-assisted vaginal hysterectomies during the study period. Analyzing the duration of surgery and rate of complications, we decided on a cutoff of 30 cases. Eight surgeons with more than 30 cases performed 668 laparoscopic-assisted vaginal hysterectomies. Their initial 30 cases (group A, the first 30 cases) were compared with their subsequent cases (group B, cases 31 and after). Patient age, body mass index, and uterine weight did not differ between the groups. The intraoperative complication rate dropped from 4.2% to 0.5% (P =.001), hemoglobin drop decreased from -0.8 +/- 0.9 g/L to -0.5 +/- 1.0 g/L (P =.002), and postoperative complications dropped from 12.9% to 7.0% (P =.017). The duration of surgery was also shorter (148.8 +/- 45.4 minutes versus 125.1 +/- 46.5 minutes), but this difference was taken from the results of 1 surgeon. CONCLUSION: A learning experience of 30 laparoscopic-assisted vaginal hysterectomies was necessary in our institution to reach a low level of complications. Duration of the surgical procedure was not an adequate study endpoint to assess a learning effect.

Adult↗

[Laparoscopic colorectal surgery. Five-year experience at Huddinge University Hospital].

By education of one to two surgeons at the time we limit the learning curve and reduce the complications. 250 patients have been operated for both benign and malignant colorectal diseases. The operation time is still longer than with the open technique. Conversion rate is 18 per cent, no mortality and few serious complications are seen. The blood loss is in mean 150 ml. With shorter time at the operation theatre through optimal education of the hole operation team, the costs for laparoscopic colorectal surgery will diminish. In the future with better laparoscopic technique, we believe there will be increased numbers of total colectomies and operations in the small pelvic.

Blood Loss, Surgical↗

[Use of a virtual immersion computer simulator as a model for basic training in laparoscopic urology].

BACKGROUND: to date, it has not been defined the best method for teaching urologic laparoscopy, however it is well recognized that it involves a steep learning curve. METHODS: A course of Laparoscopic Urology was done in our Institute. The program included skill practices in a virtual immersion simulator which evaluated, the score and time to complete each activity. This was done in a group of residents with previous experience with this virtual simulator (group 1) and another group of residents with no experience (group 2). Four different basic tasks were performed in the virtual simulator, which included: coordination, cutting, clip application and performing a simple suture. RESULTS: When we compared the scores between both groups the mean scores for each task were superior in group 1 compared to the group 2, with no statistically significant difference, however when we compared the time to complete each task, it was shorter in group 1 compared to group 2 with a statistically significant difference. CONCLUSIONS: The performance of residents without experience in a virtual simulator was similar to that of previously trained residents, however it takes less time to complete each task as the resident gains experience in these simulators. The use of virtual simulators for laparoscopy training are useful when learning basic techniques allowing the surgeon to improve hand dexterity and coordination in laparoscopic surgery.

Computer Simulation↗

Radiofrequency assisted liver resection--a novel technique.

Surgical resection remains the curative procedure for liver tumors, but even with improvements in method it is still a major operation with significant morbidity and mortality in experts' hands, and a long learning curve for those surgeons who undertake it. Recently radiofrequency ablation has gained some credibility as an alternative method of dealing with liver tumors deemed unresectable. A novel technique of liver resection assisted by the application of radiofrequency is described here. A patient with colorectal liver metastases underwent a segment II/III liver resection with this technique. Following laparotomy, the tumor was identified with intraoperative ultrasound and a 'cooled-tipped' radiofrequency probe was used to ablate liver parenchyma 2cm away from the edge of the tumor. To achieve full thickness of radiofrequency ablation, several insertions were applied. The effect of radiofrequency on liver parenchyma was monitored with an intraoperative ultrasound by micro-bubbles generated by radiofrequency ablation. The length of the resection was 45 min with a blood loss of 30mL. The patient was discharged on the 6th postoperative day without complications. In this report we indicate how the use of radiofrequency ablation can be combined with standard surgical resection of liver cancers to provide a quick, and relatively bloodless operation that is likely to reduce morbidity and mortality and is easy for its practitioners to learn.

Aged↗

Enhanced detection of nucleus basalis magnocellularis lesion-induced spatial learning deficit in rats by modification of training regimen.

Bilateral excitotoxic lesions of the nucleus basalis magnocellularis (NBM) in the rat cause deficits in the water maze, a spatial memory paradigm. Previous investigations aimed at reversing the water maze performance deficit with anticholinesterase treatments have been unable to demonstrate a consistent drug effect due to the relatively good acquisition of the task seen following NBM lesions. The present investigation tested three different water maze training regimens designed to separate the learning curves. F-344 rats received bilateral NBM injections of ibotenic acid; sham-operated rats served as controls. The animals were tested in three groups in the water maze as follows: (1) four trials per day with no intertrial interval (standard paradigm), (2) four trials per day with a 10-minute intertrial interval, and (3) two trials per day with no intertrial interval. Each group was tested in the water maze for five consecutive days, followed by two days of rest, and then tested for an additional five days. The two-trial per day paradigm was more difficult than the standard paradigm for both lesions and controls and yielded the most difference between lesions and controls as compared to the other two testing regimens. The 10-min intertrial interval schedule was more difficult than the standard paradigm for lesioned animals but acquisition was not affected in control rats. These data demonstrate that the nucleus basalis lesions cause a deficit in the water maze task regardless of training parameters. Further, while all rats showed some acquisition of the water maze task, training schedule affected the level of learning of both lesioned and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The neuroprotective effects of Cerebrolysin in a transgenic model of Alzheimer's disease are associated with improved behavioral performance.

Cerebrolysin is a peptide mixture with neurotrophic effects that might have the ability of both reducing amyloid burden and improving synaptic plasticity in Alzheimer's disease (AD). In order to determine if Cerebrolysin is capable of ameliorating the neurodegenerative and behavioral alterations associated with amyloid beta (A beta) production; transgenic (tg) mice expressing mutant human amyloid precursor protein (APP) under the Thy1 promoter were treated with Cerebrolysin or saline alone starting at 3 or 6 months of age for a total of three months. Animals were then tested behaviorally (at 6 and 9 months of age respectively) in the water maze and then analyzed neuropathologically for amyloid burden, synaptic density, astrogliosis and apoptosis. Performance analysis in the water maze showed that in the younger tg mice cohort, Cerebrolysin treatment significantly ameliorated the performance deficits. In the older cohort, there was a trend toward improved performance in the learning curve. Neuropathological examination showed that in both age/treatment groups, Cerebrolysin promoted synaptic regeneration, and reduced the proportion of neurons displaying DNA fragmentation by the (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method. Moreover, Cerebrolysin treatment reduced A beta burden by 43% in the young group and by 27% in the older group. Taken together, these results suggest that Cerebrolysin treatment might have beneficial effects in patients with cognitive impairment by reducing A beta accumulation and promoting the preservation of synaptic terminals.

Alzheimer Disease↗

The role of multimedia interactive programs in training for laparoscopic procedures.

BACKGROUND: The application of minimally invasive techniques to the performance of abdominal surgery by general surgeons has been perhaps the greatest advance in the history of general surgery. The safe adoption of many of these procedures, however, has been hampered by significant obstacles, mainly due to the problem of providing adequate training for surgeons. Outside of animal and cadaver labs, most training has been didactic in nature, and adoption rates after completion of these courses are discouraging. Multimedia interactive training has been used in a number of high-tech industries with great success. A >60% improvement in the learning curve after multimedia interactive training, as compared to traditional didactic training, has been reported. Multimedia interactive training programs for surgeons that use content and input from multiple experts in laparoscopic procedures have now been developed. METHODS: Residents from a general surgery residency program who used these programs were asked to rate their effectiveness in increasing their knowledge and comfort level prior to their participation in a real procedure as the primary surgeon or first assistant. A comparison to other traditional training techniques was also made. Eleven residents completed 41 programs designed to teach one of five different laparoscopic procedures-cholecystectomy, fundoplication, appendectomy, colon resection, or hernia repair. RESULTS: On a scale of 1 to 10, with 10 being the highest, the residents reported that the multimedia interactive training programs raised their knowledge level of the procedure from 6.0 to 8.7 (+2.7 point value increase after using the multimedia interactive program). The programs increased their comfort level when actually called on to perform or assist with the procedure from 5.3 to 8.1 (+2.8 point value increase after using the multimedia interactive program). In comparing the value of training methods for learning laparoscopic procedures, the residents rated text, lectures, videos, and animal labs at 4.7, 5.1, 6.0 and 7.3, respectively. By comparison, the residents rated the multimedia interactive training program at 8.8. CONCLUSION: The use of multimedia interactive training programs in addition to current laparoscopic training courses may help to increase the safe adoption of laparoscopic procedures. These programs may be a beneficial adjunct to residency training programs.

Adult↗

Establishing stable test performance in tests from the Behavioral Assessment and Research System (BARS).

Research to identify adverse effects in humans chronically exposed to neurotoxic substances in the workplace or environment typically assesses people at one point in time in a cross-sectional study. The most widely used strategy employs performance measures taken from a single point in time and compares these with either performance of a control group or established normative data. However, multiple comparison points of the same people on the same test allow the dissection of acute--from chronic--exposure effects, among other important questions. When performance measures are used from multiple points in time, within-subject deviations are examined. For either research design, the goal is to minimize the effects of practice and to obtain stable performance on a test. Demographic variables such as age, education, and cultural background or ethnicity influence performance on neurobehavioral tests. These variables may also influence the development of stable performance. Different populations may have different learning curves so that stable performance on a test is achieved with different amounts of practice. This is especially important when making comparisons across groups that may not have equivalent backgrounds. The performance of three groups, English-speaking adults, Spanish-speaking adolescents, and Spanish-speaking migrant adolescents, was examined. Each group completed a battery of neurobehavioral tests from the Behavioral Assessment and Research System (BARS) during four sessions. Repeated measures ANOVAs were used to investigate performance across time. Tests measuring motor performance produced stable performance from the first session. More complex tasks that involved attention and memory showed a practice effect across sessions.

Adolescent↗

Fitness to work of astronauts in conditions of action of the extreme emotional factors.

The theoretical model for the quantitative determination of influence of a level of emotional exertion on the success of human activity is presented. The learning curves of fixed words in the groups with a different level of the emotional exertion are analyzed. The obtained magnitudes of time constant T depending on a type of the emotional exertion are a quantitative measure of the emotional exertion. Time constants could also be of use for a prediction of the characteristic of fitness to work of an astronaut in conditions of extreme factors. The inverse of the sign of influencing on efficiency of activity of the man is detected. The paper offers a mathematical model of the relation between successful activity and motivations or the emotional exertion (Yerkes-Dodson law). Proposed models can serve by the theoretical basis of the quantitative characteristics of an estimation of activity of astronauts in conditions of the emotional factors at a phase of their selection.

Animals↗

Acquiring surgical skills: a comparative study of open versus laparoscopic surgery.

OBJECTIVES: A preliminary study to evaluate the feasibility of a protocol for comparing the learning curves for open and laparoscopic surgical procedures. PARTICIPANTS AND METHODS: Thirteen pre-clinical medical students with no previous surgical training were given intensive coaching in open and laparoscopic surgical techniques for 12 weeks. At the end of this period, their open and laparoscopic skills were assessed by three independent examiners. Individual and aggregate ability scores in various aspects of open and laparoscopic surgery and the time taken to perform the procedures were compared using Student's t-test. RESULTS: There was no statistically significant difference in the overall scores by the two different techniques ( p=0.057 ). However, differences between the two techniques were significant in certain criteria including tissue dissection (p=0.024), tidiness of gall bladder (p=0.034 ) and liver ( p=0.016 ) specimens and the time taken for the two techniques ( p < or = 0.001 ). CONCLUSIONS: This study suggests that when inexperienced subjects are given equal training in laparoscopy and open surgery, the overall skills acquired were similar by both methods when assessed after 6 weeks. However, on detailed analysis of the different components of surgery, the laparoscopic skills were deficient in finer dissection, identification of correct planes and two-dimensional perception when compared to open surgery and required more operative time. Our study group perceived that laparoscopy was more difficult to learn than open surgery even after the training. The study group also felt that the training in basic surgical skills during their undergraduate careers would make them more interested in studying surgery and choosing it as a career.

Animals↗

Selective Reminding Tests: a normative study of verbal learning in adults.

Verbal learning was assessed according to the Selective Reminding Test (SRT) in order to establish normative data and to provide a comparison with measures of immediate attention, verbal IQ, and verbal memory. The 392 subjects, stratified by sex (202 women, 190 men), age (4 groups: 16-70 years), and education (3 groups), were free of conflicting pathologies. Learning curves were established on centiles (75, 50, 25, 5). Sex differences favoring women were found in percent of finishers (those who reached criterion), and at all percentile levels of acquisition. Data were analyzed for group differences in performance on the SRT and related concurrent measures, but sex differences were not found on the VIQ or immediate attention tests. Also, assumptions of age and education stratification were not confirmed. However, those who completed the task were better able to form associational strategies than those who were unable to finish. The present data indicate that it is important to use detailed norms by gender and criterion level if clinical interpretations are to be valid.

Adolescent↗

A history of psychiatric ethics.

In the not-far-distant past, ethics for all doctors was, at best, an ill-attended lecture or two on how to keep out of trouble; it was assumed the rest was absorbed by a form of social and professional osmosis. Although ethics has entered the undergraduate curriculum, continuing medical education programs, journals, and books, it still is in a state of flux. Although immense progress has been made in the last 30 to 40 years, much remains to be done. Trainees are often naïve, and the older generation is on a steep learning curve. An encouraging feature is the current lively debate on matters ethical and how they can best be incorporated into everyday clinical practice. The long-held notion of ethics resting complacently in the paternal arms of Hippocrates has, with almost brutal haste, been projected into a rapidly evolving modern world of technologic, moral, and societal change. Yet, at its core, ethics has to retain its humanism and guard against influences from every quarter that tries to make it a set of rules, thereby negating the diversity and uniqueness of our patients. Even as you read, there will be new influences and pressures on clinical practice that have an ethical dimension. For instance, we are adjusting to new privacy laws in Australia that allow patients, whether public or private, access to their psychiatric records. Globalization is not restricted to world trade; it also operates in the framework of societal change and the wider dissemination and implementation of libertarian views. If such "freedoms" are not currently available to patients, they soon will be. This brief historical foray in identifying some of these forces can assist in their early recognition so that as a profession, we are forewarned and forearmed and, in that respect, be ahead of both Henry Ford ("History is more or less bunk...") [42] and the Bourbons ("They learn nothing and they forget nothing") [43].

Ethics, Medical↗

The quantitative evaluation of functional neuroimaging experiments: the NPAIRS data analysis framework.

We introduce a data-analysis framework and performance metrics for evaluating and optimizing the interaction between activation tasks, experimental designs, and the methodological choices and tools for data acquisition, preprocessing, data analysis, and extraction of statistical parametric maps (SPMs). Our NPAIRS (nonparametric prediction, activation, influence, and reproducibility resampling) framework provides an alternative to simulations and ROC curves by using real PET and fMRI data sets to examine the relationship between prediction accuracy and the signal-to-noise ratios (SNRs) associated with reproducible SPMs. Using cross-validation resampling we plot training-test set predictions of the experimental design variables (e.g., brain-state labels) versus reproducibility SNR metrics for the associated SPMs. We demonstrate the utility of this framework across the wide range of performance metrics obtained from [(15)O]water PET studies of 12 age- and sex-matched data sets performing different motor tasks (8 subjects/set). For the 12 data sets we apply NPAIRS with both univariate and multivariate data-analysis approaches to: (1) demonstrate that this framework may be used to obtain reproducible SPMs from any data-analysis approach on a common Z-score scale (rSPM[Z]); (2) demonstrate that the histogram of a rSPM[Z] image may be modeled as the sum of a data-analysis-dependent noise distribution and a task-dependent, Gaussian signal distribution that scales monotonically with our reproducibility performance metric; (3) explore the relation between prediction and reproducibility performance metrics with an emphasis on bias-variance tradeoffs for flexible, multivariate models; and (4) measure the broad range of reproducibility SNRs and the significant influence of individual subjects. A companion paper describes learning curves for four of these 12 data sets, which describe an alternative mutual-information prediction metric and NPAIRS reproducibility as a function of training-set sizes from 2 to 18 subjects. We propose the NPAIRS framework as a validation tool for testing and optimizing methodological choices and tools in functional neuroimaging.

Adult↗

Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats.

Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.

Aging↗