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Valine, isoleucine, and leucine. A new treatment for phenylketonuria.

Early treatment of phenylketonuria by dietary phenylalanine restriction prevents brain damage. Behavioral and cognitive deficits occur when serum phenylalanine levels increase. Administration of valine, isoleucine, and leucine to patients with phenylketonuria may inhibit entry of phenylalanine into the brain and reduce its toxic effects on the central nervous system. Sixteen adolescents and young adults with phenylketonuria participated in double-blind trials in which a valine, isoleucine, and leucine mixture or a control mixture was given for four 3-month periods. Biochemical and neuropsychologic tests were carried out before and at the end of each period. Time to completion of a test that required substantial attention with mental processing (Attention Diagnostic Method) was faster during the valine, isoleucine, and leucine periods than during the control mixture periods. Improvement with valine, isoleucine, and leucine on a less demanding task (Continuous Performance Test) approached significance. These data lent support to the hypothesis that a regimen of valine, isoleucine, and leucine may help individuals unable to maintain low serum phenylalanine levels.

Adolescent↗

Children at risk for schizophrenia. Clinical and attentional characteristics.

Adolescent high-risk subjects, offspring of schizophrenic mothers, who were placed in foster homes at an early age, are compared with foster children whose biological parents have no record of psychiatric hospitalization and with non-foster children. The high-risk group showed increased social isolation, difficulties in the student role, elevated total symptom scores on the Psychiatric Status Schedule, and elevated schizophrenic scale scores on the Minnesota Multiphasic Personality Inventory. Half of the high-risk subjects showed significant impairment on a battery of eight attention-demanding tasks.

Adolescent↗

P3 in schizophrenia is affected by stimulus modality, response requirements, medication status, and negative symptoms.

Eighteen schizophrenics who were not taking medication, 13 schizophrenics who were taking medication, and 37 age-matched controls were tested with event-related potential paradigms designed to elicit P3 response automatically or effortfully (ie, with a choice reaction time task). Electroencephalograms were recorded from the 19 standard 10-20 electrode sites. Compared with controls, both groups of schizophrenics had reduced P3 amplitudes for both effortful and automatic paradigms. P3 latencies were delayed relative to controls for the medication-taking schizophrenics in the effortful paradigms. Negative symptoms derived from the Brief Psychiatric Rating Scale within 1 week of event-related potential testing correlated negatively with both auditory and visual P3 amplitude in the subjects who were not taking medication. There was no evidence that P3 is smaller over left temporal electrode sites in schizophrenics, as has been reported by others. P3 amplitude reduction in schizophrenia is a robust psychobiological phenomenon that is present regardless of medication status or task demands.

Adult↗

A functional magnetic resonance imaging study of tic suppression in Tourette syndrome.

BACKGROUND: The inability to inhibit unwanted behaviors and impulses produces functional debility in a broad range of neuropsychiatric disorders. A potentially important model of impulse control is volitional tic suppression in Tourette syndrome. METHODS: Tic suppression was studied in 22 adult subjects with Tourette syndrome by using functional magnetic resonance imaging. Images acquired during periods of voluntary tic suppression were compared with images acquired when subjects allowed the spontaneous expression of their tics. The magnitudes of signal change in the images were then correlated with measures of the severity of tic symptoms. CONCLUSIONS: Significant changes in signal intensity were seen in the basal ganglia and thalamus and in anatomically connected cortical regions believed to subserve attention-demanding tasks. The magnitudes of regional signal change in the basal ganglia and thalamus correlated inversely with the severity of tic symptoms. These findings suggest that the pathogenesis of tics involves an impaired modulation of neuronal activity in subcortical neural circuits.

Adolescent↗

Awareness predicts the magnitude of single-cue trace eyeblink conditioning.

Studies of differential eyeblink conditioning (CS+ and CS-) have demonstrated that successful conditioning requires awareness of the stimulus contingencies and that delay conditioning does not. Two experiments were carried out to determine whether awareness is also important for single-cue trace eyeblink conditioning. In experiment 1, participants who performed a secondary, attention-demanding task emitted significantly fewer conditioned eyeblink responses than participants who watched a silent movie during the conditioning session. In experiment 2, participants who became aware of the stimulus contingencies early in the conditioning session emitted significantly more conditioned responses during the remainder of the session than participants who became aware later in the session or who never became aware. These results indicate that awareness is important for single-cue trace eyeblink conditioning, just as it is for differential trace conditioning. The relationship between awareness and trace eyeblink conditioning is discussed in the light of these and other recent findings.

Aged↗

Differential workloads of boys and girls in rural Nepal and their association with growth.

In developing countries, heavy workloads of women adversely affect their nutritional status and that of their children. Little is known, however, about the effect of children's heavy workloads on their own well-being. In Nepal, girls are expected to help their mothers in time-consuming and energy-demanding tasks from an early age. The aim of this study was to compare work patterns and anthropometric status of boys and girls age 6-17 years in western rural Nepal. It was hypothesized that girls would work longer and harder than boys and would have poorer growth status. It was also anticipated that children's work patterns might differ between highland and lowland areas. Two study sites were therefore chosen: one in the hills and the other in the lowland terai. A time allocation study was conducted for 237 children. They were observed continuously from 7:00 AM to 7:00 PM to determine the time spent in light, moderate, and heavy activities. Body weights and heights were also measured. On average, girls worked twice as long as boys (5.8 vs. 2.8 h/day, P < 0.001) and undertook more heavy work (1.5 vs. 0.7 h/day, (P < 0.001), but they did not have poorer anthropometric status. Children in the hills worked longer hours and did heavier work than those in the terai and were more stunted in growth.

Adolescent↗

Self-injurious behavior in young boys with fragile X syndrome.

In this study, we distributed surveys to 67 families of young boys with fragile X syndrome to determine the prevalence, onset, form, function, location, and correlates of self-injurious behavior. Fifty-five surveys were completed (82%). The mean age of the boys at the time of the survey was 80 months (range = 20-144). Self-injurious behavior (SIB) was reported for 58% of the participants with a mean age of onset of 31 months. The mean number of forms of self-injury was 2 per participant. Biting was the most commonly reported form of self-injury with the fingers and back of the hand disproportionately targeted as the most prevalent self-injury body site. There was no linear increase in risk of SIB with age past 25 months. SIB was reported as most likely to occur following the presentation of difficult task demands or changes in routine. Significant group differences were found between overall ratings of problem behavior for boys with self-injury compared to those without self-injury. Groups did not differ on measures of fragile X mental retardation protein (FMRP), autism status, adaptive behavior, or age first medicated. Results are discussed in terms of future research designed to further elucidate the behavioral phenotype of fragile X syndrome.

Age Factors↗

Measurement of eye-gaze in chimpanzees (Pan troglodytes).

Gaze cues are used as an index of social cognition in primates, yet the sensitivity to different forms of gaze, and consequently the cues required to test gaze-following abilities remain understudied. Whereas the eye is attributed special signal value in humans, the camouflaged ocular morphology of non-human primates has led to the consensus that head orientation may be a more salient cue. This study presents the first documentation of the surface eye movements of the chimpanzee, Pan troglodytes, in order to determine the behavioral forms of eye-gaze and their saliency as signals, document their functional variation, and address the signal value of the eyes distinct from head orientation. Movements of the eye were identified as Scan (continuous movement), Glance (a single movement <1 sec), or Fixate (no movement). Scans, glances, and fixations were reliably detected by humans during live observation and from video (Cohen's kappa over 0.70) and, therefore, are likely also to be detected by conspecifics. Eye-gaze comprised a nonunitary measure of visual attention, reflecting the attentional task demands of different activities. Specifically, chimpanzees spent significantly more time scanning while feeding and resting, than grooming, F(2,28) = 10.23, P<0.001, and spent significantly more time fixating while grooming, than feeding or resting, F(2,28) = 7.52, P<0.01. Further, eye-gaze was often incongruent with head movement, varying significantly with the form of eye-gaze: incongruence was found during 12-21% of fixations, during 42-49% of scans, and during 70-100% of glances, F(2,16) = 30.17, P<0.001. These findings provide the basis for discrimination of the adaptive significance of gaze-processing abilities with emphasis on sensitivity to eye-gaze distinct from head orientation. If we are to continue exploring gaze-processing abilities in primates, then we need greater consideration of the precise nature of the signals themselves. Here we present evidence for special consideration of the eyes as a salient signal in P. troglodytes.

Animals↗

The human immunodeficiency virus reduces network capacity: acoustic noise effect.

OBJECTIVE: Increased acoustic noise (AN) during working memory leads to increased brain activation in healthy individuals and may have greater impact in human immunodeficiency virus (HIV) patients. RESULTS: Compared with control subjects, HIV patients showed reduced AN activation and lower neuronal marker N-acetylaspartate in prefrontal and parietal cortices. Competing use of the working memory network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients. INTERPRETATION: These findings suggest that reduced reserve capacity of the working memory network in HIV patients and additional stress (eg, AN) might exhaust the impaired network for more demanding tasks.

Acoustic Stimulation↗

Cognitive deficits in Machado-Joseph disease.

Cognitive function was examined in 6 patients with genetically confirmed Machado-Joseph disease (MJD) and 15 age- and ethnically matched controls using a series of subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), a touch screen-based testing system previously validated in a number of movement and neurodegenerative disorders. The MJD patients had deficits in visual attentional function that were characterized by a slowing of the processing of visual information when task demands were high and an inability to shift attention to previously irrelevant stimulus dimensions to discriminate between complex stimuli. Tests of learning and visual memory were normal. These results demonstrate that specific cognitive deficits occur in patients with MJD, independent of motor dysfunction, and these deficits may reflect disruption to frontosubcortical pathways.

Adult↗

Cascade reactions in total synthesis.

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Biological Products↗

Sound localization in newborn human infants.

Newborns' localization of sounds was examined in two experiments that utilized different psychophysical procedures and imposed different task demands. The results of both experiments were consistent in indicating that neonates not only differentiate the hemifield of a sound source but have some capacity to localize a sound within the hemifields. Adjustment of their initial head turn angle following a within-hemifield shift in location of an ongoing sound indicated that head orientation in neonates is elicited not only by sound onset but also by changes in location of an ongoing sound. Thus, multiple stimulus parameters impact on this neonatal response. Results are related to research on sound localization in older infants, and discussed in light of early development of the central auditory system.

Arousal↗

Hippocampal place cells, context, and episodic memory.

Although most observers agree that the hippocampus has a critical role in learning and memory, there remains considerable debate about the precise functional contribution of the hippocampus to these processes. Two of the most influential accounts hold that the primary function of the hippocampus is to generate cognitive maps and to mediate episodic memory processes. The well-documented spatial firing patterns (place fields) of hippocampal neurons in rodents, along with the spatial learning impairments observed with hippocampal damage support the cognitive mapping hypothesis. The amnesia for personally experienced events seen in humans with hippocampal damage and the data of animal models, which show severe memory deficits associated with hippocampal lesions, support the episodic memory account. Although an extensive literature supports each of these hypotheses, a specific contribution of place cells to episodic memory has not been clearly demonstrated. Recent data from our laboratory, together with previous findings, indicate that hippocampal place fields and neuronal responses to task-relevant stimuli are highly sensitive to the context, even when the contexts are defined by abstract task demands rather than the spatial geometry of the environment. On the basis of these findings, it is proposed that place fields reflect a more general context processing function of the hippocampus. Hippocampal context representations could serve to differentiate contexts and prime the relevant memories and behaviors. Since episodic memories, by definition, include information about the time and place where the episode occurred, contextual information is a necessary prerequisite for any episodic memory. Thus, place fields contribute importantly to episodic memory as part of the needed context representations. Additionally, recent findings indicate that hippocampal neurons differentiate contexts at progressively finer levels of detail, suggesting a hierarchical coding scheme which, if combined with temporal information, could provide a means of differentiating memory episodes.

Action Potentials↗

The impact of glucose ingestion and gluco-regulatory control on cognitive performance: a comparison of younger and middle aged adults.

A great deal of research has been devoted to the issue of whether the ingestion of a glucose containing drink facilitates cognitive performance. However, it remains unclear exactly how age and individual differences in gluco-regulatory control mediate a boost in cognitive functioning. The present study investigates these issues further. A repeated measures (25 g vs 50 g glucose vs placebo) counterbalanced, double-blind design was used with 25 younger and middle-aged adults. A battery of memory and non-memory tasks was administered; including tests of episodic and semantic memory, attention and visuospatial functioning. Glucose ingestion largely facilitated performance on tasks with a memory component. Notably, task demands and age (young vs middle-aged) contributed to the magnitude of memory enhancement. This finding suggests an age- and load-specific benefit of glucose intake. In addition, evidence suggests greater facilitation in individuals with good glucose regulation. These data are discussed in relation to the idea that glucose specifically affects neural mechanisms supporting memory functioning (i.e. the hippocampus), which are known to decline in ageing. Importantly, the present investigation adds to the growing body of literature showing the utility of glucose supplementation as memory enhancers.

Adolescent↗

Psychological aspects of lay caregiving.

Caregiving is an extremely demanding task that frequently takes a toll on lay caregivers. Furthermore, the psychological aspects of caregiving are frequently overlooked. To study this issue, a nurse surveyor conducted an informal nonscientific survey of 68 lay caregivers over a 14-month period. An interview process was used to obtain information. Those who were surveyed identified depression, powerlessness, role strain, guilt, and grief as the psychological aspects most frequently related to the caregiving experience. This information can be used to initiate nursing care plans, assessments, and interventions. It is vital for the healthcare community to recognize the needs of lay caregivers. Training programs must be implemented and other support and resources should be available so that the needs and issues of lay caregivers can be dealt with effectively.

Adaptation, Psychological↗

Unique selective detectors for gas chromatography: nitrogen and sulfur chemiluminescence detectors.

Many of present day's complex analyses and challenging analytical tasks demand highly selective detection techniques for GC. Universal nitrogen/sulfur chemiluminescence detection is one of the most powerful analytical tools for gas chromatographic analysis. Its strength stems from the unique and beneficial characteristics of high selectivity, sensitivity, and equimolarity. The nitrogen/sulfur chemiluminescence detection technology has provided analytical solutions unsurpassed by any other techniques to a broad range of applications in petroleum characterization, food/beverage flavor analysis, and environmental monitoring. This paper presents a general review of this unique technology, including a brief description of operating principles, an overview of detector performance, practical discussions on instrument operation, and a sizable list of applications.

Chromatography, Gas↗

Clinical impairment of sequential finger movements in Parkinson's disease.

A retrospective analysis was performed on the records of 33 off-therapy parkinsonian patients. We analyzed the clinical score of three sequential upper limb movements: finger tapping, hand opening and closing, and forearm pronation and supination. The records showed that nearly all patients had difficulty in performing all three motor tasks, but movement scores showed that they found the sequential finger-tapping task significantly more difficult than the other two tasks. We suggest that parkinsonian patients find individual finger movements more difficult to execute than gross hand movements because--owing to their abnormal basal ganglia output--they lack the finer cortical control and greater facilitation that the finger task demands.

Aged↗

Intelligent transport systems and occupational therapy practice.

This paper explores some of the most widely available in-vehicle information technology systems (intelligent transport systems, or ITSs) and discusses their implications for occupational therapy practice. Therapists often evaluate the impact of functional impairment on driving ability and, with an ageing population, the need for such assessments is increasing. Concurrently, ITSs are becoming increasingly common and it is important that their potential effects on both driving task demand and crash risk are considered by therapists when assessing drivers. Interactions between drivers and ITSs are analysed in an information processing framework, highlighting the importance of drivers' cognitive functioning. It is evident that the ability to use an ITS while driving is influenced by a driver's sensory, perceptual, cognitive and motor capacities and skills, all of which are likely to vary with age, disability and/or driving experience. The compatibility of ITS interface design with drivers' capacities and needs is crucial in determining how effectively, and safely, a particular system will be used. Therapists need to analyse interface demands in relation to the ability of individual drivers to cope with or benefit from an ITS, and to consider the potential for calibrating particular products to the specific requirements of individual drivers. It is concluded that many ITSs are at an early stage of development and should not be recommended without critical evaluation of their utility, usability and safety for the intended users. Therapists face the challenge of understanding the parameters and implications of ITSs so that they can assist their clients to optimize their occupational performance despite functional limitations, while also protecting the safety of other road users. Standards related to interface design are still undergoing development, and there is an urgent need for further research to evaluate the impact of vehicle technologies on human behaviour and road safety.

Automobile Driving↗