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Effects of aluminum exposure on behavioral parameters in the rat.

Adult rats were treated by intraperitoneal injection of aluminum gluconate for 3 months. Rats were submitted to the radial maze test to determine the influence of chronic aluminum intoxication on cognitive and noncognitive behavioral processes. Both learning abilities (working memory and reference memory) and rapidity (time spent to respond and to master a trial) were analyzed. Aluminum concentration was evaluated in the brain, serum, and liver to assess aluminum body burden. While hippocampus and neocortex showed a significant increase in aluminum concentration, aluminum treatment did never affect the animal's performance during cue learning or when the insert cues were removed. The only behavioral difference observed was a decrease in rapidity: both the total time to finish a trial and the latency to make the first choice were lengthened in aluminum-intoxicated rats.

Aluminum Compounds↗

A dietary supplement abolishes age-related cognitive decline in transgenic mice expressing elevated free radical processes.

We previously found that transgenic mice overexpressing growth hormone (TGM) have elevated and progressively increasing free radical processes in brain that strongly correlates with reduced survivorship. Young mature TGM, however, displayed vastly enhanced learning of an eight-choice cued maze and qualitatively different learning curves than normal controls. Here we document the age-related patterns in learning ability of TGM and normal mice. Learning appeared inferior in both genotypes of very young mice but TGM were confirmed to be superior to normal mice upon maturity. Older TGM, however, showed rapid age-related loss of their exceptional learning, whereas normal mice at 1 year of age showed little change. The cognitive decline of TGM was abolished by a complex "anti-aging" dietary supplement formulated to promote membrane and mitochondrial integrity, increase insulin sensitivity, reduce reactive oxygen and nitrogen species, and ameliorate inflammation. Results are discussed in the context of reactive oxygen and nitrogen species, long-term potentiation, learning, aging and neuropathology, based on known impacts of the growth hormone axis on the brain, and characteristics of TGM.

Aging↗

Conserving total synaptic weight ensures one-trial sequence learning of place fields in the hippocampus.

The hippocampus plays a critical role in the rapid acquisition of information from a novel experience. Recent theoretical studies on the rat hippocampus have shown the possibility of behavioral sequence learning in a single traversal experience by theta phase coding. Specifically, previous work using computer simulations demonstrated that the extent of overlap among individual events of sequence and rat running velocity should be quantitatively incorporated into the learning rule to ensure one-trial sequence learning. These extents of overlap- and running velocity-dependent properties in the learning rule are called the input-dependent regulation of the learning rule. However, the biological meaning of such learning properties remains poorly understood. In this study, we quantitatively derive these learning properties with mathematical analyses. We further find that the input-dependent regulation of the learning rule allows maintenance of total synaptic weight over a given neuron during one-trial learning. Our results predict that a homeostatic plasticity mechanism should exist for conserving total synaptic weight on a rapid timescale.

Action Potentials↗

WilsonGenAI a deep learning approach to classify pathogenic variants in Wilson Disease.

BACKGROUND: Advances in Next Generation Sequencing have made rapid variant discovery and detection widely accessible. To facilitate a better understanding of the nature of these variants, American College of Medical Genetics and Genomics and the Association of Molecular Pathologists (ACMG-AMP) have issued a set of guidelines for variant classification. However, given the vast number of variants associated with any disorder, it is impossible to manually apply these guidelines to all known variants. Machine learning methodologies offer a rapid way to classify large numbers of variants, as well as variants of uncertain significance as either pathogenic or benign. Here we classify ATP7B genetic variants by employing ML and AI algorithms trained on our well-annotated WilsonGen dataset. METHODS: We have trained and validated two algorithms: TabNet and XGBoost on a high-confidence dataset of manually annotated, ACMG & AMP classified variants of the ATP7B gene associated with Wilson's Disease. RESULTS: Using an independent validation dataset of ACMG & AMP classified variants, as well as a patient set of functionally validated variants, we showed how both algorithms perform and can be used to classify large numbers of variants in clinical as well as research settings. CONCLUSION: We have created a ready to deploy tool, that can classify variants linked with Wilson's disease as pathogenic or benign, which can be utilized by both clinicians and researchers to better understand the disease through the nature of genetic variants associated with it.

Hepatolenticular Degeneration↗

Client satisfaction with rapid HIV testing: comparison between an urban sexually transmitted disease clinic and a community-based testing center.

Rapid HIV testing allows same-day results, increasing the number of persons who learn their HIV status. Understanding how clients in different settings perceive rapid testing may increase acceptance of this technology. From June 1999 to August 2001 we interviewed 256 clients at a publicly funded urban sexually transmitted disease (STD) clinic and 1201 clients at a community- based HIV counseling, testing, and referral center (Los Angeles Gay and Lesbian Center; LAGLC) about their posttest satisfaction with rapid HIV testing. HIV prevalence was 3.9% at the STD clinic and 5.3% at the LAGLC. In multivariate analysis, adjusting for age, sexual orientation, race/ethnicity, history of STDs, self-perceived HIV risk, prior HIV test and HIV testing results, clients at the STD clinics (versus LAGLC) were more likely to find testing stressful (adjusted odds ratio [AOR]: 1.75, 95% confidence limits [CL]: 1.27, 2.42) and feel that they received their results too quickly (AOR: 2.05, 95% CL: 1.39, 3.03). Latinos (versus whites) were more likely to report that they received their results too quickly (AOR: 4.99, 95% CL: 3.48, 7.14) and that it would be better to wait a week for HIV test results (AOR: 2.48, 95% CL: 1.51, 4.09). Further research may elucidate the reasons why some groups prefer to wait for results, and enable policymakers to better design strategies to reach high-risk groups with rapid HIV testing.

AIDS Serodiagnosis↗

A partial agonist at strychnine-insensitive glycine sites facilitates spatial learning in aged rats.

1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity ligand at strychnine-insensitive glycine sites of the N-methyl-D-aspartate (NMDA) channels and exhibits partial agonist properties in both biochemical and electrophysiological measures. While ACPC was reported active in animal models used to evaluate potential antidepressants and anxiolytics, its effects on learning and memory are unknown. In the present study we investigated the effects of ACPC on spatial learning in the Morris water maze. On a schedule of 12 learning trials, one trial per day, mature male Wistar rats (3 months of age) rapidly acquired the task. Electroconvulsive shocks applied after each of the learning trials markedly inhibited the consolidation of spatial memory. Administration of either a muscarinic agonist, arecoline (1 mg/kg) or ACPC (250 or 400 mg/kg) 20 min before each of the learning trials did not affect the acquisition of spatial learning. Aged (16 months old) male Wistar rats demonstrated difficulties in the acquisition of spatial learning task. In these subjects, ACPC administered 20 min before each of the learning trials at a dose of 400, but not 250 mg/kg, facilitated the acquisition of spatial memory as indicated on trials 3-5. ACPC did not affect the strength of spatial memory as assessed at the end of conditioning, by measuring swimming behavior of rats in the pool with platform removed. It is suggested that ACPC may alleviate learning deficits observed in the elderly.

Age Factors↗

Effect of D-cycloserine on rapid tolerance to ethanol.

We recently reported that the noncompetitive NMDA antagonists, (+)MK-801 and ketamine, block the development of rapid tolerance to ethanol. In the present article, we show that D-cycloserine (CS), an agonist at the glycine site of the NMDA receptor that enhances learning and memory, also enhances the development of rapid tolerance to ethanol. Rats were pretreated on day 1 with saline or CS, followed 30 min later by ethanol (2.3 g/kg, IP) or saline. At the end of motor impairment testing on the tilt-plane apparatus, a second injection of CS (3 mg/kg, IP, each time) or saline was given, followed 30 min later by ethanol or saline. Ethanol pretreatment alone (at this dose) did not result in rapid tolerance to ethanol on day 2. However, the group pretreated with CS and ethanol on day 1 showed significant tolerance on day 2 compared to other groups. Pretreatment with CS on day 1 did not affect the motor impairment response to the first exposure to ethanol whether this was on day 1 or day 2. In another experiment, administration of (+)MK-801 (0.25 mg/kg, IP) prior to CS abolished the rapid tolerance enhancement by CS. These findings are further evidence that the NMDA system, which requires activation by the glycine receptor, plays a major role in the development of at least some forms of ethanol tolerance.

Animals↗

Computer-assisted learning versus a lecture and feedback seminar for teaching a basic surgical technical skill.

BACKGROUND: Rapid improvements in computer technology allow us to consider the use of computer-assisted learning (CAL) for teaching technical skills in surgical training. The objective of this study was to compare in a prospective, randomized fashion, CAL with a lecture and feedback seminar (LFS) for the purpose of teaching a basic surgical skill. METHODS: Freshman medical students were randomly assigned to spend 1 hour in either a CAL or LFS session. Both sessions were designed to teach them to tie a two-handed square knot. Students in both groups were given knot tying boards and those in the CAL group were asked to interact with the CAL program. Students in the LFS group were given a slide presentation and were given individualized feedback as they practiced this skill. At the end of the session the students were videotaped tying two complete knots. The tapes were independently analyzed, in a blinded fashion, by three surgeons. The total time for the task was recorded, the knots were evaluated for squareness, and each subject was scored for the quality of performance. RESULTS: Data from 82 subjects were available for the final analysis. Comparison of the two groups demonstrated no significant difference between the proportion of subjects who were able to tie a square knot. There was no difference between the average time required to perform the task. The CAL group had significantly lower quality of performance (t = 5.37, P <0.0001). CONCLUSIONS: CAL and LFS were equally effective in conveying the cognitive information associated with this skill. However, the significantly lower performance score demonstrates that the students in the CAL group did not attain a proficiency in this skill equal to the students in the LFS group. Comments by the students suggest that the lack of feedback in this model of CAL was the significant difference between these two educational methods.

Computer-Assisted Instruction↗

Behavior and learning problems in epileptic children.

In this modern age of rapidly advancing medical knowledge and technology there are few conditions as wrapped up in ignorance and prejudice as that known as epilepsy. A large part of the reason for this lies in the concept of the "epileptic person," by which is really meant the epileptic personality. In an attempt to assess behavior and learning in children with seizures, behavior and learning being regarded as opposite sides of the same coin, a study was designed in which totally objective neurological and psychological data was obtained from such a group of children. The evaluation was carried out without any prior knowledge of the nature of the presenting clinical picture, so as to prevent bias from pre-conceived notions. The results show that 70% of the first 200 children showed significant learning defects sufficient to make special educational placement mandatory. Of the remaining 30% some still showed minor learning problems enough to give rise to difficulties in regular classroom situations. Associated with these learning problems were varying behavioral reaction types, varying from the classical hyperactive child with minimal cerebral dysfunction to many environmentally-produced behavior difficulties resulting from faulty school placement due to failure to recognize learning problems. Faculty parental handling due to similar failure to realize the child's limitations also contributed to this. The significance of these findings with respect to the behavior disturbances of the so-called epileptic child will be discussed.

Adolescent↗

Rapid electrical and delayed molecular signals regulate the serum response element after nerve injury: convergence of injury and learning signals.

Axotomy elicits changes in gene expression, but little is known about how information from the site of injury is communicated to the cell nucleus. We crushed nerves in Aplysia californica and the sciatic nerve in the mouse and found short- and long-term activation of an Elk1-SRF transcription complex that binds to the serum response element (SRE). The enhanced short-term binding appeared rapidly and was attributed to the injury-induced activation of an Elk1 kinase that phosphorylates Elk1 at ser383. This kinase is the previously described Aplysia (ap) ERK2 homologue, apMAPK. Nerve crush evoked action potentials that propagated along the axon to the cell soma. Exposing axons to medium containing high K(+), which evoked a similar burst of spikes, or bathing the ganglia in 20 microM serotonin (5HT) for 20 min, activated the apMAPK and enhanced SRE binding. Since 5HT is released in response to electrical activity, our data indicate that the short-term process is initiated by an injury-induced electrical discharge that causes the release of 5HT which activates apMAPK. 5HT is also released in response to noxious stimuli for aversive learning. Hence, apMAPK is a point of convergence for injury signals and learning signals. The delay before the onset of the long-term SRE binding was reduced when the crush was closer to the ganglion and was attributed to an Elk1 kinase that is activated by injury in the axon and retrogradely transported to the cell body. Although this Elk1 kinase phosphorylates mammalian rElk1 at ser383, it is distinct from apMAPK.

Action Potentials↗

Cooperative learning: a model for teaching.

Cooperative learning provides a socially and intellectually stimulating model for the instruction of nursing students. It is one method of encouraging students to take responsibility for their own learning. Students are often able to explain a concept to another student in a unique way not used by faculty. This model harnesses and directs that student input in a constructive manner to increase achievement and accountability for all involved. Faculty must continue to examine how nursing is taught. The world is changing far too rapidly to do "business as usual." Cooperative learning is one strategy that can be used to motivate students to take active and responsible roles in their learning.

Cooperative Behavior↗

[Percutaneous nephrostolithotomy. Technic and learning curve].

The closed controlled manipulation of the urinary tract (endourology) has provided rapid advances in urologic therapy. Various methods are available for percutaneous stone removal. After 300 p.c. nephrostolithotomies we present the 'learning curve' leading to our technique of endourologic stone manipulation.

Humans↗

Rapid prefrontal-hippocampal habituation to novel events.

Unexpected novel events generate an orienting response that plays an important role in some forms of learning and memory. The orienting response involuntarily captures attention and rapidly habituates as events become familiarized. Although evidence from patients with focal lesions and scalp and intracranial event-related brain potential recordings supports the involvement of a distributed neural network involving association cortex and the limbic system in novelty detection, the key neural substrates and temporal dynamics have not been defined. While subjects performed a bi-field visual-selective attention task with random novel stimuli embedded in either attended or unattended visual fields, we measured rapid changes of regional blood oxygenation level-dependent (BOLD) signal to target and novel stimuli using single-trial analysis of event-related functional magnetic resonance imaging with a 4T scanner. Habituation was quantified by serial BOLD signal changes during the first 10 novel stimuli for each subject. Novel stimuli activated the bilateral superior/middle frontal gyrus, temporal-parietal junction, superior parietal lobe, cingulate gyrus, hippocampus, and fusiform gyrus. The superior/middle frontal gyrus and hippocampus showed significant reduction of BOLD signal during the first few novel stimuli, whereas the signals in the fusiform and cingulate gyrus were constant. Prefrontal and hippocampal responses to attended and unattended novel stimuli were comparably habituated. These results, and previous data from lesion studies, support the view that prefrontal and hippocampal regions are involved in rapid automatic detection and habituation to unexpected environmental events and are key elements of the orienting response in humans.

Adult↗

Values-based leadership and organizational development during restructuring.

This article highlights the importance of value-based leadership and cultural change, and illustrates how organizational development strategies can facilitate positive learning environments. This is essential during periods of rapid change, restructuring, and downsizing, when the quality of patient care can be at risk. By ensuring a values focus, and a systematic approach to the development of a "learning organization", nurses can be empowered to develop their clinical practice and to lead the redesign of healthcare systems in a more creative and patient-centered way.

Hospital Restructuring↗

The role of stimulus comparison in perceptual learning: an investigation with the domestic chick.

In two experiments an imprinting procedure was used to familiarize chicks with two stimuli, A and B, that subsequently served as the discriminanda in a simultaneous discrimination. On the first day of each experiment, subjects either received presentations of A and B that were intermixed within a session (mixed exposure) or presentations of A in one session and of B in another (separate exposure). For half of the subjects in each of the exposure conditions, A and B differed in both colour and form; for the remainder A and B differed in form alone. On the second day of the experiments, the chicks were placed into a cool test apparatus and given training in which approaching A was rewarded by the delivery of a stream of warm air, but approaching B was not. Acquisition of this discrimination was more rapid when A and B differed in two respects than when they differed in form alone. When A and B differed in both colour and form, the heat-reinforced discrimination was acquired more rapidly after separate exposure than after mixed exposure; but when A and B differed in form alone, discrimination learning was more rapid following mixed exposure than separate exposure. The latter finding, that the opportunity to compare stimuli differing in only one dimension facilitates subsequent discrimination learning, is consistent with earlier suggestions (Gibson, 1969) regarding the conditions that promote perceptual learning.

Animals↗

Chile's national nutritional supplementation program for older people: lessons learned.

Demographic changes in developing countries have resulted in rapid increases in the size of the older population. As a result, health-care budgets face increasing costs associated with the declining health and function of older people. Some governments have responded to this situation by designing innovative programs aimed at older people. One such program, implemented by the government of Chile, distributes an instant food mix fortified with vitamins and minerals to all persons over 70 years old who are registered by the national health service. The national health service covers approximately 90% of the older population. The program specifically targets nutritional vulnerability and micronutrient deficiency, which are common among poor older people in Chile. We present here the findings of a one-year investigation into all aspects of Chile's program for the elderly. The research included in-depth interviews with policy makers and program implementers, focus group discussions with user groups, analysis of the micronutrient content of the nutritional supplement, and telephone interviews of a random sample of older people. The results demonstrate that there can be a considerable degree of self-targeting within national programs; programs need to be sufficiently flexible to permit periodic protocol change; user groups must be consulted both before and during program implementation; and the design of an effective program evaluation must be in place before program implementation. It is hoped that these results will be useful to policy makers and implementers planning programs aimed at improving the health and function of older people.

Aged↗

Rapid HIV testing with same-day results: a field trial in Uganda.

Rapid, on-site HIV testing with same-day results may improve services and increase the number of clients who learn their serostatus in developing countries. To validate test performance under field conditions and assess the change in the proportion of clients who learn their serostatus, we conducted a field trial using the Capillus HIV-1/HIV-2 assay (Cambridge Diagnostics) at the AIDS Information Centre counselling and testing sites in Uganda. Compared to the standard 2-EIA testing algorithm, the sensitivity of Capillus was 99.6% (95% CI; 98.5%, 99.9%), the specificity was 98.8% (95% CI; 98.1%, 99.3%), the positive predictive value was 96.5% (95% CI; 94.5%, 97.8%), and the negative predictive value was 99.9% (95% CI; 99.5%, 100%). It took less than 5 min to perform a single test, and results were returned to clients in less than an hour, during which time clients were counselled. This resulted in a 27% increase in the proportion of clients who learned their serostatus and received counselling. We conclude that simple, rapid HIV tests can be performed accurately on-site within the time frame of a clinic visit, increasing the number of clients who learn their serostatus and receive post-test counselling.

HIV Infections↗

Watching the brain during meaning acquisition.

Acquiring the meaning of a new word in a foreign language can be achieved either by rote memorizing or, similar to meaning acquisition during infancy, by extracting it from context. Little is known about the brain mechanisms involved in word learning. Here we demonstrate, using event-related brain potentials, the rapid development of a brain signature related to lexical and semantic processing during contextual word learning. Healthy volunteers engaged in a simple word-learning task were required to discover the meaning of a novel word from a context during silent reading. After 3 exposures, brain potentials to novel words in meaningful contexts were indistinguishable from real words, although this acquisition effect was not observed for novel words, for which sentence contexts allowed no meaning derivation. Furthermore, when the learned novel words were presented in isolation, an activation of their corresponding meaning was observed, although this process was slower than for real words.

Adult↗