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PubMed2004

Neurological and cognitive impairment associated with leaded gasoline encephalopathy.

BACKGROUND: A toxic encephalopathy (or 'lead encephalopathy') may arise from leaded gasoline abuse that is characterised by tremor, hallucinations, nystagmus, ataxia, seizures and death. This syndrome requires emergency and intensive hospital treatment. METHODS: We compared neurological and cognitive function between chronic gasoline abusers with (n=15) and without (n=15) a history of leaded gasoline encephalopathy, and with controls who had never abused gasoline (n=15). RESULTS: Both groups of chronic gasoline abusers had abused gasoline for the same length of time and compared to controls, showed equivalently elevated blood lead levels and cognitive abnormalities in the areas of visuo-spatial attention, recognition memory and paired associate learning. However, where gasoline abusers with no history of leaded gasoline encephalopathy showed only mild movement abnormalities, gasoline abusers with a history of leaded gasoline encephalopathy showed severe neurological impairment that manifest as higher rates of gait ataxia, abnormal rapid finger tapping, finger to nose movements, dysdiadochokinesia and heel to knee movements, increased deep tendon reflexes and presence of a palmomental reflex. CONCLUSIONS: While neurological and cognitive functions are disrupted by chronic gasoline abuse, leaded gasoline encephalopathy is associated with additional and long-lasting damage to cortical and cerebellar functions.

Administration, Inhalation↗

PubMed2026

Large language models in bioinformatics: a comprehensive survey.

The emergence of foundation models with trillion-level parameters has redefined the landscape of artificial intelligence. Various fields are developing their own large-scale models, which can solve many problems within the field and improve work efficiency. Biological large-scale models are a cross-disciplinary research field that combines mathematics, computer science, and biology, aiming to simulate and understand the structure, function, and dynamic changes of biological systems through the establishment of complex computational models. This field covers multiple levels such as biological pathways, population dynamics, protein folding, etc., providing us with tools for deep exploration of the mysteries of life and applications in medicine, ecology, and other fields. This article reviews the background and research status of biological large-scale models, and discusses future directions. Large language models (LLMs) and other large-scale foundation models have rapidly advanced in recent years, enabling powerful representation learning and generation across text, sequences, and multimodal data. In bioinformatics and biomedicine, these models are increasingly used to analyze genomic sequences, infer protein properties and structures, support drug discovery, and integrate heterogeneous biomedical evidence. This survey reviews the basic principles of LLMs and summarizes representative applications in (i) gene and genome sequence analysis, (ii) protein structure and function prediction, and (iii) drug design, including virtual screening and personalized medicine. We also discuss emerging multi-model modeling approaches, as well as key challenges such as data quality and privacy, interpretability, generalization to new organisms and tasks, and responsible deployment in health-related settings. Finally, we outline future directions for developing reliable, scalable, and explainable bioinformatics foundation models.

bioinformatics↗

PubMedDate not supplied

Information systems and human error in the lab.

Health system costs in clinical laboratories are incurred daily due to human error. Indeed, a major impetus for automating clinical laboratories has always been the opportunity it presents to simultaneously reduce cost and improve quality of operations by decreasing human error. But merely automating these processes is not enough. To the extent that introduction of these systems results in operators having less practice in dealing with unexpected events or becoming deskilled in problemsolving, however new kinds of error will likely appear. Clinical laboratories could potentially benefit by integrating findings on human error from modern behavioral science into their operations. Fully understanding human error requires a deep understanding of human information processing and cognition. Predicting and preventing negative consequences requires application of this understanding to laboratory operations. Although the occurrence of a particular error at a particular instant cannot be absolutely prevented, human error rates can be reduced. The following principles are key: an understanding of the process of learning in relation to error; understanding the origin of errors since this knowledge can be used to reduce their occurrence; optimal systems should be forgiving to the operator by absorbing errors, at least for a time; although much is known by industrial psychologists about how to write operating procedures and instructions in ways that reduce the probability of error, this expertise is hardly ever put to use in the laboratory; and a feedback mechanism must be designed into the system that enables the operator to recognize in real time that an error has occurred.

Clinical Laboratory Information Systems↗

PubMed1997

Adding value: what healthcare can learn from industry.

How can superior outcomes be provided to satisfied patients using the appropriate amount of resources? That's the $64,000 question that healthcare organizations are striving to answer--indeed, must answer--to survive in the managed care marketplace, says Stephen Shortell, Ph.D., A.C. Buehler Distinguished Professor of Health Services Management of Northwestern University. The business world can teach healthcare leaders how to increase their organizations' competitive edge, he says, in four areas: having a deep knowledge of the customer, looking for ways to add value, using innovation as a key to adding value and defining value in economic terms.

Consumer Behavior↗

PubMed2002

A clinical focus on feeling in dreams.

This article, a posthumous presentation of a work in progress of Walter Bonime, one of the maverick thinkers of psychoanalysis of the 20th century, gives us a clear picture of a step-by-step use of feelings in dreams to facilitate the working through process in psychoanalysis. Through a series of dreams occurring during a finite period of the working through process the author shows us how he utilizes the feelings in the dreams to facilitate associations. By connecting past dreams with the actual one being discussed plus writing about his own associations to present and past dreams, while using confrontation and clarification Bonime gives us a clear picture of his day-to-day creative process of collaboration with his patient. As an incomplete work, still in its draft form, this article has the richness of a work in progress. It allows us a clear view of the work of a seasoned, innovative, engaged, and committed analyst with a patient through time, work mainly anchored in his deep understanding of the human psyche, his creative use of dreams, and his commitment to helping the other evolve into his/ her best sense of self.

Adult↗

PubMedDate not supplied

Influence of sports background on leg muscle coordination in vertical jumps.

This study was planned to investigate the influence of sports background on leg muscle coordination during vertical jumps (concentric and drop jumps). Five different athlete groups were chosen as subjects: jumpers in athletics, swimmers, soccer players and poor and good vertical jumpers. Motor versatility was used as an additional inclusion criterion. Interest centred on the comparison of two different movement models: the jumping model (jumpers) and the kicking model (swimmers). The jumpers performed the most powerful vertical jumps. Proportional IEMG activity showed that their catapult innervation did not follow the proximo-distal model. The jumpers exemplified the stiffness innervation typical of power athletes. The swimmers turned out to be the poorest jumping group. Their agonist muscle coordination resembled more the simultaneous than sequential proximo-distal model. Furthermore, the agonist and antagonist muscles of both the thigh and shank showed co-contraction instead of reciprocal innervation. The simultaneous model adopted by all the leg muscles and a tendency to produce a new burst of activity at the end of the contact phase seem to be associated with the posture and stiffness demands of swimming performance. The soccer players showed an intermediate innervation, including a sequential flow of activity, but also a poor reciprocal function and a tendency to produce a new burst of activity at the end of the contact phase. The DDJ-type activity coordination of the poor and good vertical jumpers (Deep Drop Jump, Eloranta 1997b) most resembled the stereotypical proximo-distal flow of activity of the vertical jump (Bobbert and van Ingen Schenau 1988). The results suggest that prolonged training in a specific sport will cause the central nervous system (CNS) to program muscle coordination according to the demands of that sport. That learned skill-reflex (automatic skill program, Eloranta 1997b) of the CNS seems to interfere hierarchically in the performance program of another task. Therefore, it is reasonable to believe that human movement behavior is characterized by previously learned skill-reflexes.

Adult↗

PubMedDate not supplied

Semantic paralexias facilitated by tachistoscopic reading in a patient with impairment of phonological recoding.

This study of a dyslexic patient supports the view that the level of impairment of the phonological route plays a role in the production of semantic paralexias. The patient's reading was based on a defective phoneme-to-grapheme transcoding, in spite of evidence that semantic information was available through non phonological routes. The hypothesis that the residual ability to carry out phonological recoding could block the production of semantic paralexias was confirmed by tachistoscopic reading, assumed to interfere with phonological recoding in this patient, that provoked a definite rise of this type of error. The relationship between the degree of damage of phonological route and the clinical expression of the syndromes of phonological dyslexia and deep dyslexia is also discussed.

Adaptation, Psychological↗

PubMed2006

Chronic deep brain stimulation of the subthalamic nucleus for Parkinson's disease: effects on cognition, mood, anxiety and personality traits.

OBJECTIVE: To evaluate modifications occurring in cognitive functions and behavioural aspects in a group of 72 consecutive patients with Parkinson's disease (PD) 15 months after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). METHODS: 72 consecutive PD patients bilaterally implanted for DBS of the STN were evaluated before and after surgery with a mean follow-up of 15 months. A neuropsychological assessment was performed to evaluate reasoning (Raven Colour Matrices), memory (Bisyllabic Word Repetition Test, Corsi's Block-Tapping Test, Paired-Associate Learning) and frontal executive functions (Trail Making Test Part B, Nelson Modified Card Sorting Test, phonemic and category verbal fluency tasks). Mood and suicidal ideation were evaluated using the Beck Depression Inventory (BDI). Anxiety was measured by means of the State-Trait Anxiety Inventory and personality traits were evaluated with the Structured Clinical Interview for the DSM-III-R Axis II Disorders (SCID-II). Assessment of thought disorders and apathy was based on subitems of the Unified Parkinson's Disease Rating Scale. RESULTS: The comparisons between pre- and postoperative neuropsychological test scores showed a significant worsening only in phonemic and semantic verbal fluency tasks, while fewer errors were found in the Nelson Modified Card Sorting Test. Globally, behavioural assessment evidenced a small improvement in mood, as assessed by the BDI, in obsessive-compulsive and paranoid personality traits (SCID-II). Thought disorders worsened while suicidal ideation, anxiety and apathy showed no postoperative modifications. The analysis of individual outcomes (+/-1 SD criterion) evidenced a relevant postoperative cognitive decline in 3 patients out of 65 (4.5%). Moreover, following implantation, 1 patients exhibited psychosis (1.5%), 2 patients experienced a clinically relevant worsening of depressive symptoms (3%), 7 patients showed an increase in anxiety (12%) and 3 patients a worsening in depression and anxiety symptoms (3%). On the contrary, 12 patients (20%) showed a relevant improvement in mood and 14 patients (23%) a relevant reduction of anxiety symptoms after the surgery. CONCLUSIONS: The present study confirms that STN DBS is cognitively safe since the only relevant change observed was a mild decrease in verbal fluency tasks. Globally, a small postoperative improvement was found in the BDI, and in two SCID-II subscales concerning obsessive-compulsive and paranoid personality traits, even though postoperative behavioural disturbances can occur in individual patients.

Affect↗

PubMed1986

Spontaneous alternation and habituation in a t-maze in nervous mutant mice.

Nervous mutant mice have a selective degeneration of Purkinje cells and deep cerebellar nuclei. In comparison with littermate controls, nervous mutant mice did not alternate spontaneously in a successive trial procedure (six consecutive trials per day) and did not habituate in a restricted part of a t-maze in a 4-min session. These data indicate that the cerebellum may have a role in spatial learning.

Animals↗

PubMed1993

Robust detection of below-lesion, non-invasive electromyographic signals.

In the majority of people experiencing "complete" spinal cord injury (total or near total para or quadraplegic) some small percentage of axons survive across the site of injury (lesion). Although the response from this small population of neurons is insufficient to facilitate active motor functions, neural impulses are potentially transmitted, under volitional control, below the level of the spinal cord injury. The ability to use these impulses to augment residual muscle functions, control the environment, or to reinforce the learning of new actions, would have profound implications on the rehabilitation and social reintegration of people with spinal cord or other neurological injuries. This investigation develops signal processing techniques for subthreshold electromyographic (EMG) signals, collected non-invasively (without breaking the skin) and below-lesion (below the spinal cord injury). Such signals are buried deep in noise, but the signal (motor unit action potential trains) and noise (spurious neuronal firings and biological interference) are shown to be separable using nonlinear techniques for which the usual signal to noise ratio is irrelevant. Then, controllers based on these techniques will enable the use of weak neural impulses to perform functions necessary for self reliant existance, and will lead to development of prosthetic/orthotic control methodologies.

Adult↗

PubMed2001

Generalization, similarity, and Bayesian inference.

Shepard has argued that a universal law should govern generalization across different domains of perception and cognition, as well as across organisms from different species or even different planets. Starting with some basic assumptions about natural kinds, he derived an exponential decay function as the form of the universal generalization gradient, which accords strikingly well with a wide range of empirical data. However, his original formulation applied only to the ideal case of generalization from a single encountered stimulus to a single novel stimulus, and for stimuli that can be represented as points in a continuous metric psychological space. Here we recast Shepard's theory in a more general Bayesian framework and show how this naturally extends his approach to the more realistic situation of generalizing from multiple consequential stimuli with arbitrary representational structure. Our framework also subsumes a version of Tversky's set-theoretic model of similarity, which is conventionally thought of as the primary alternative to Shepard's continuous metric space model of similarity and generalization. This unification allows us not only to draw deep parallels between the set-theoretic and spatial approaches, but also to significantly advance the explanatory power of set-theoretic models.

Bayes Theorem↗

PubMed2000

Neural circuits and topographic organization of the basal ganglia and related regions.

The present review was attempted to analyze the multiple channels of basal ganglia-thalamocortical connections, and the connections of their related nuclei. The prefrontal and motor areas consist of a number of modules, which seem to provide multiple subloops of the basal ganglia-thalamocortical connections in subhuman primates. There may be a great degree of convergence of the limbic, associative and motor loops at the level of the striatum, substantia nigra, pallidum, and the subthalamic nucleus as well as the pedunculopontine nucleus. Nigral dopaminergic neurons receive limbic input directly as well as indirectly through the striosomes in the striatum. Dopamine contributes to behavioral learning by signaling motivation and reinforcement. The pedunculopontine nucleus might be involved in behavioral state control, learning and reinforcement processes, locomotion and autonomic functions. Each subdivision of the motor areas receives a mixed and weighted transthalamic input from both the cerebellum and basal ganglia. In particular, based on the author's data, the hand/arm motor area and adjacent premotor area receive strong superficial basal ganglia-thalamocortical projections as well as the deep cerebello-thalamocortical projections. These areas, have very dense corticocotrical connections with other cortical areas, receive polymodal afferents from the parietal and temporal cortices, and integrated information, via multiple routes, from the prefrontal cortex. The author suggests that the ventrolateral part of the caudal medial pallidal segment (GPi) and the ventromedial part of the GPi are linked directly to these areas by ways of the oral part of ventral lateral nucleus (VLo) and the ventral part of the parvicellular part of ventral anterior nucleus (VApc), respectively. These connections are thought to be involved in the acquisition and coordination of motor sequences.

Animals↗

PubMed1982

Thalamic inputs to cytochrome oxidase-rich regions in monkey visual cortex.

In primate primary visual cortex, staining for cytochrome oxidase reveals a regular array of blob-like structures, most prominent in layers II and III but also present in layers V and VI. In an attempt to learn more about the input to these blobs, we injected the lateral geniculate bodies of macaques and squirrel monkeys with [3H]proline or horseradish peroxidase and looked in the cortex for transported label. As expected, label was present in layers IVa, IVc alpha, IVc beta, and VI. In addition, both methods revealed an array of puffs deep in layer III. Seen in tangential sections, the puffs precisely matched the cytochrome blobs. These results indicate a projection from the lateral geniculate body to the blob regions deep in layer II/III, either indirect via layer IV or more likely direct. In area 18 stained for cytochrome oxidase, we also observed complex banding patterns; these were remarkably similar to the pattern found after [3H]proline or horseradish peroxidase injection and were also similar to the pattern produced with 2-deoxyglucose labeling after stimulation with vertical or horizontal stripes; the proline and peroxidase labels probably represent a projection from the pulvinar to area 18.

Animals↗

PubMed2001

What we can learn from heavy ion therapy for radioprotection in space.

A major problem in manned space flight is the impact of cosmic radiation, especially that of heavy charged particles since they have an elevated biological efficiency (RBE). The RBE estimation determines the potential exposure for man. It is one of the limiting factors for space flight and should be known very precisely. The same is true for heavy-ion tumor therapy where beams of carbon ions are used to treat deep-seated tumors. There, RBE values determine the dose distribution and are estimated using the Local Effect Model (LEM). The clinical results confirm the correctness of LEM and suggest to use the same theoretical approach to assess the impact of cosmic rays.

Carbon↗

PubMed1991

Writing with the right hemisphere.

We studied writing abilities in a strongly right-handed man following a massive stroke that resulted in virtually complete destruction of the language-dominant left hemisphere. Writing was characterized by sensitivity to lexical-semantic variables (i.e., word frequency, imageability, and part of speech), semantic errors in writing to dictation and written naming, total inability to use the nonlexical phonological spelling route, and agrammatism in spontaneous writing. The reliance on a lexical-semantic strategy in spelling, semantic errors, and impaired phonology and syntax were all highly consistent with the general characteristics of right hemisphere language, as revealed by studies of split-brain patients and adults with dominant hemispherectomy. In addition, this pattern of writing closely resembled the syndrome of deep agraphia. These observations provide strong support for the hypothesis that deep agraphia reflects right hemisphere writing.

Agraphia↗

PubMed2003

New perspectives on dystonia.

Dystonia is a syndrome of sustained muscular contractions with numerous underlying etiologies. This review examines the varied phenomenology of dystonias, its evolving classification including recent genetic data as well as its clinical investigation and treatment. Although age of onset, anatomical distribution and family history are key elements of the investigation of dystonia, classification increasingly relies on etiologic and genetic criteria. Physiological abnormalities in striato-cortical circuits are common in dystonia but the pathophysiology is still unclear. In recent years, a great deal has been learned on the more common primary dystonias such as primary torsion dystonia and on dystonia-plus syndromes such as dopamine responsive dystonia. Treatment of dystonia has also evolved and there are now a number of therapeutic agents with clear beneficial effects including anticholinergics, benzodiazepines, and botulinum toxin and there is growing interest in neurofunctional surgery including deep brain stimulation.

Blepharospasm↗

PubMed2005

Atypical neuropsychological profile in a boy with 22q11.2 Deletion Syndrome.

In this article the general and specific cognitive impairments of the boy R.H. with a de novo deletion 22q11.2 are described. His full-scale IQ was 73, and he obtained only slightly better verbal than non-verbal subtest scores. Neuropsychological assessment revealed specific impairments in perceptual categorization of objects presented suboptimal, matching of unfamiliar faces, and verbal learning and memory. In contrast, he performed in accordance with his intelligence level on other visual perceptual tasks, on non-verbal learning and memory tasks, and on attention tasks. Voxel-wise statistical comparison of a high-resolution T1-weighted magnetic resonance image of R.H's brain with similar images obtained from 14 normal control children revealed as major abnormalities a reduction of the right inferior parietal and superior occipital lobe, and a bilateral reduction of deep white matter behind the inferior frontal gyrus. These cognitive impairments and MRI abnormalities are not commonly described in 22q11.2 Deletion Syndrome and may indicate a larger heterogeneity in the neurocognitive phenotype than currently evidenced. At least in this boy the microdeletion seems to have interfered with the development and functioning of particular neural subsystems, while the structure and functioning of other subsystems was left intact.

Attention Deficit Disorder with Hyperactivity↗

PubMed1996

[The influence of psychological factors on the patient's management of diabetes. Critical survey of psychodynamic models on personal management of diabetes].

The authors have examined the currently accepted methods to face a chronic disease like diabetes. The person affected by this illness should learn to accept his/her limits and find a new identity. The aim of technical and scientific medicine is to teach the patient how to cope with the disease. However, in spite of the progress of the scientific research in this field, diabetes remains a poorly treated disease. A review of the literature shows that there is a deep interaction between diabetes and psychological states. Psychological disorders like depression and anxiety might be associated with the origin of diabetes and can affect its course. It seems that emotional factors have a more important role than education in diabetes care. The psychological aspect becomes even more important during adolescence, as the chronic illness can affect the normal development of the teen-ager who will deny it to protect himself. If the patient does not collaborate, his behaviour may be unconsciously aggressive and destructive. Some patients can use diabetes as a tool to act out aggressive feelings against themselves or the environment. Diabetes bad management becomes then the expression of their destructive narcissism which prevents them from finding a new identity. The collaboration of medical and psychological operators should help these patients to find a new identity which includes diabetes as an integrating part of their personality and enables them to cope with it under the guidance of the diabetes team.

Adaptation, Psychological↗