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At least 217 records · Page 12Linked to original sources
PubMed1979

Lead poisoning without encephalopathy. Effect of early diagnosis on neurologic and psychologic salvage.

Medical and psychological status of 166 patients previously treated for lead poisoning and of 22 sibling controls were evaluated. Maximum blood lead levels ranged from 40 to 471 microgram/dL. Eighteen patients had definite symptoms, 32 had questionable symptoms, and 116 were asymptomatic. No patients developed seizures, other neurological sequelae, or abnormal nerve conduction velocity. No statistically significant relationship was found between blood lead concentration (PbB) and subsequent intellectual function. The mean IQ of the patient cohort was 87, approximately at the 50th percentile for inner-city schoolchildren in Chicago. Detection prior to encephalopathy and prompt detoxification were effective in preventing or minimizing sequelae despite high PbBs.

Brain Diseases↗
PubMed1996

Combination therapy in rheumatoid arthritis: the animal model perspective.

Attempts to improve antirheumatic agent efficacy have resulted in exploration of treatment protocols with combinations of 2 or more agents. Hypothetically, an ideal combination therapy would have greater efficacy and less toxicity than any of its component agents used individually. However, even a limited number of available drugs can produce a daunting number of possible combination protocols, each requiring clinical evaluation. Intelligent selection of combination protocols, based on a firm understanding of each agent's specific mechanism(s) of action, may help identify potentially useful regimens. Autoimmune animal models of inflammatory synovitis provide a unique opportunity to study the etiology, pathophysiology, and treatment of rheumatoid arthritis (RA). Induction of chronic inflammatory synovitis in susceptible inbred strains can allow for in vivo study under reproducible controlled conditions, using experimental protocols not possible in humans. Although animal models can only approximate human rheumatic disease in its complete form, they are nonetheless important for developing new therapeutic strategies. We review the 3 most common animal models of RA, the streptococcal cell wall, adjuvant, and collagen arthritis rat models. Surprisingly, few published studies evaluate combination therapy in RA animal models. We discuss these investigations, which use interventions aimed at angiogenesis, microtubule function, and immune regulation, as examples of animal models to assess and develop effective therapeutic combinations of antirheumatic agents.

Animals↗
PubMed1996

Aspirin and other nonsteroidal anti-inflammatory agents in the prevention of colorectal cancer.

Chemoprevention refers to the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent the progression to invasive cancer. The ideal chemopreventive agent is safe and nontoxic over the long term. It should be easy to take and demonstrated to be effective in randomized trials in humans. Aspirin and NSAIDs meet many of the criteria for an ideal agent. The literature on aspirin and NSAIDs makes it clear that these agents can prevent colorectal cancer and precursor adenomas. That does not mean that we should make general recommendations for their use. First, we do not know the proper dose or duration. More important, these medications are accompanied by adverse effects that can be considerable. Indeed, the Medical Letter, an authoritative, unbiased publication on drugs and therapeutics, concluded that "for primary prevention in low-risk patients, more studies are required to establish whether the beneficial effect of aspirin is great enough to compensate for the possible increased risk of hemorrhagic stroke." These recommendations were directed at the use of these medications for prevention of myocardial infarction, but the same conclusions apply to colorectal cancer: although aspirin may prevent the disease, it may increase the risk of hemorrhagic strokes or cause other adverse effects. We must accurately balance the benefits and risks of these drugs, based on the results of ongoing randomized studies, before recommending aspirin for prevention of colorectal cancer. Is there anything that we can recommend to our patients for prevention of colorectal cancer? Based on observational epidemiologic studies, it is clear that individuals who consume a diet high in vegetables and natural fibers and low in fat have a reduced risk of colon cancer and polyps. Optimal nutrient intakes for the prevention of cancer might be more readily achieved via food fortification or supplementation, but this requires more research. Regular physical exercise and maintenance of normal body weight are also protective. Until the results of definitive studies of chemopreventive agents are available, we can recommend that our patients eat a sensible diet, exercise, and avoid obesity. Such an approach should protect them from cardiovascular disease, an even deadlier condition than colorectal cancer. In the future, we need randomized prevention trials that, for logistic reasons, may need to focus on the occurrence and progression of colorectal adenomas rather than carcinoma itself. Studies that test more than one compound at a time, using factorial designs, will be more efficient. We will need better information about duration and dose, adverse side effects, molecular mechanisms, and cellular sites of NSAID activity. Ultimately, we will need to know more about the biology and molecular biology of colorectal cancer and its precursors. That information will, perhaps, permit us to design agents to interrupt the pathway to cancer and to use intermediate markers more intelligently.

Adenocarcinoma↗
PubMed2004

[How bacteria resist antibiotics: a primary form of collective intelligence?].

Bacteria produce inhibitory enzymes (beta-lactamases, etc), block antibiotic attachment to target molecules (MRSA, etc.), extrude antibiotics from the cell by active efflux systems (multidrug resistant pseudomonas, etc) or limit antibiotic penetration through the outer membrane in Gram negatives. Genetically, resistance occurs after mutation or horizontal transfers (transformation, transduction, conjugation) of mobile genetic elements (integrons, transposons, phages, plasmids), associated with a risk of epidemic spread. Recent data stress the importance pheromones for facilitating inter-bacterial genetic exchanges. Activated by quinolones and penicillins the SOS response augments the mutation rate (by about 10,000 fold) and liberates mobile genetic elements offering more opportunities to select resistance. These highly pertinent non-darwinian systems raise the hypothesis of a primary form of intelligence developed already 3.8 billions years ago.

Anti-Bacterial Agents↗
PubMed1998

Medical affective computing: medical informatics meets affective computing.

"The need to cope with a changing and partly unpredictable world makes it very likely that any intelligent system with multiple motives and limited powers will have emotions." [1] From advisory systems that understand emotional attitudes toward medical outcomes, to wearable computers that compensate for communication disability, to computer simulations of emotions and their disorders, the research agendas of medical informatics and affective computing--how and why to create computers that detect, convey, and even have emotions--increasingly overlap. Some psychiatric and neurological researchers state their theories in terms of actual or hypothetical computer programs. Adaptive intelligent systems will increasingly rely on emotions to compensate for their own conflicting goals and limited resources--emotional reactions about which psychiatrists and neurologists have special insights. DEP2 (Depression Emulation Program 2) is a computer simulation of adaptive depression--learning from explainable patterns of failure in autobiographical memory--that simulates many depressive behaviors. In the terminology of fault-tolerant computing, adaptive depression involves fault detection (triggered by failure), fault location (strategic retreat and failure diagnosis), and fault recovery (return to on-line operation). DEP2 relies on subsystems whose structures and behaviors are based on popular hypotheses about left and right brain hemispheric function during depression and emotion. DEP2 and its predecessors, DEP and DEPlanner, are relevant to psychiatric and neurological informatics, and to the design of adaptive autonomous robots and software agents.

Adaptation, Psychological↗
PubMed2004

An intelligence ink for oxygen.

A generic ink formulation is described, comprising semiconductor photocatalyst particles, a brightly-coloured redox dye, a mild reducing agent, a polymer and a solvent, that creates an irreversible, reusable, UV-light-activated, colorimetric indicator or intelligence ink for oxygen.

Journal Article↗
PubMed2001

Intelligent systems in the context of surrounding environment.

We investigate the behavioral patterns of a population of agents, each controlled by a simple biologically motivated neural network model, when they are set in competition against each other in the minority model of Challet and Zhang. We explore the effects of changing agent characteristics, demonstrating that crowding behavior takes place among agents of similar memory, and show how this allows unique "rogue" agents with higher memory values to take advantage of a majority population. We also show that agents' analytic capability is largely determined by the size of the intermediary layer of neurons. In the context of these results, we discuss the general nature of natural and artificial intelligence systems, and suggest intelligence only exists in the context of the surrounding environment (embodiment).

Artificial Intelligence↗
PubMed2006

The dual-use dilemma for the life sciences: perspectives, conundrums, and global solutions.

The term "dual-use" traditionally has been used to describe technologies that could have both civilian and military usage, but this term has at least three different dimensions that pose a dilemma for modern biology and its possible misuse for hostile purposes: (1) ostensibly civilian facilities that are in fact intended for military or terrorist bioweapons development and production; (2) equipment and agents that could be misappropriated and misused for biological weapons development and production; and (3) the generation and dissemination of scientific knowledge that could be misapplied for biological weapons development and production. These three different aspects of the "dual-use dilemma" are frequently confused--each demands a distinct approach within a "web of prevention" in order to reduce the future risk of bioterrorism and biowarfare. This article discusses the nature of the different perspectives and divergent approaches as a contribution to finding a scientifically acceptable global solution to the problem posed by the dual-use dilemma. We propose that: (1) facilities that are intended for bioweapons development and production should be primarily prevented by a strengthened Biological and Toxin Weapons Convention (BTWC) effectively implemented in all nation states, one that includes provisions for adequate transparency to improve confidence and a mechanism for thorough inspections when there is sufficient cause, and enhanced law enforcement activities involving international cooperation and sharing of critical intelligence information; (2) potentially dual-use equipment and agents should be available to legitimate users for peaceful purposes, but strengthened national biosafety and physical and personnel biosecurity controls in all nations together with effective export controls should be implemented to limit the potential for the misappropriation of such equipment and materials; and (3) information should be openly accessible by the global scientific community, but a culture of responsible conduct involving the breadth of the international life sciences communities should be adopted to protect the ongoing revolution in the life sciences from being hijacked for hostile misuse of the knowledge generated and communicated by life scientists.

Access to Information↗
PubMed2026

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository.

Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.

Single-Cell Analysis↗
PubMed1990

Medication monitoring in the workplace: toward improving our system of epidemiologic intelligence.

There is a great deal we do not know about the safety of pharmaceutical agents, especially regarding their safe use in the workplace. Economic and scientific imperatives can lead to a new drug's approval and marketing even though testing is limited; therefore, much of the knowledge about drug toxicities must be developed in the postapproval period, through pharmacoepidemiologic methods. The system of epidemiologic intelligence depends on spontaneous, voluntary reports of adverse drug reactions and, as applied to the work force, it is fraught with problems of ascertainment, accountability, and application. Structured epidemiologic studies of these issues have been difficult to perform because of high costs, long time frames, and methodologic problems and biases. Nevertheless, large automated data bases, with the right input, hold great promise for making it easier to accumulate and analyze the data necessary for monitoring drug safety in the workplace.

Drug Evaluation↗
PubMed1996

Computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents.

The computer-automated structure evaluation programs MultiCASE and CASE were used to perform a quantitative structure-activity relationship study on tubulin polymerization inhibitors. A learning set of 536 chemicals (202 active. 27 marginal, and 307 inactive), built using IC50 values for inhibition of tubulin polymerization or mitosis from this and previous studies, was used for artificial intelligence self-teaching. The algorithms successfully predicted the activity of agents in the learning set with > 90% accuracy. Seventeen MultiCASE and twelve CASE (mostly included in the MultiCASE set) biophores (substructures significantly correlated with activity) were identified with a probability > 0.95. Here we present the biophores of podophyllotoxins, colchicinoids, and certain combretastatins, each examined for structure-activity relationships. For the podophyllotoxins and colchicinoids in the learning set, the correlations between observed and predicted potencies were > 0.85. The algorithms recognized the importance of several known site, electronic, and steric effects in the two classes. A predictive QSAR (R2 = 0.98) was developed for combretastain A-2 and dihydrocombretastatin analogues. The MultiCASE/CASE analyzes were used in combination with molecular models to study relative orientations of colchicine, podophyllotoxin, combretastatin A-4, and steganacin at the colchicine site. This resulted in a new hypothesis, consistent with extensive published experimental data, in which the C-ring and part of the B-ring of colchicine overlap with the A- and B-rings of podophyllotoxin. Consequently, the trimethoxyphenyl rings of colchicine and podophyllotoxin occupied different regions of space, each pointing out from a hydrophobic 'core' occupied by the overlapping biophores. The molecular model of the highly potent combretastatin A-4 could fit into the model binding site in at least three different ways. The developed QSARs were used to identify the potent microtubule stabilizer discodermolide. Its identification, in concert with recently reported findings, suggest potential overlap in the colchicine and paclitaxel binding sites on tubulin.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Speech intelligibility in severe adductor spasmodic dysphonia.

This study compared speech intelligibility in nondisabled speakers and speakers with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (Botox) injection. Standard speech samples were obtained from 10 speakers diagnosed with severe ADSD prior to and 1 month following Botox injection, as well as from 10 age- and gender-matched healthy adults. This yielded 3 speaking conditions: pre-Botox injection, post-Botox injection, and normal control. Thirty phrases were extracted from the speech samples and arranged in a counterbalanced listening experiment. Thirty students, reporting little experience with distorted speech, served as listeners. Each listener's response was scored for words correctly identified using a liberal scoring criterion yielding a percentage of words correctly identified for each speaker. The results indicated that the speakers with ADSD were significantly more intelligible in the post-Botox condition than in the pre-Botox condition. The results also indicated that healthy speakers were significantly more intelligible than the speakers in both the pre- and post-Botox conditions. In general, these results indicated that intelligibility is affected in severe ADSD and that the use of Botox injection in ADSD improves intelligibility scores. However, the results also indicated that the use of Botox injection does not result in speech intelligibility similar to that of normal, non-ADSD speakers.

Acoustic Stimulation↗
PubMed2006

Pattern detection in forensic case data using graph theory: application to heroin cutting agents.

Pattern recognition techniques can be very useful in forensic sciences to point out to relevant sets of events and potentially encourage an intelligence-led style of policing. In this study, these techniques have been applied to categorical data corresponding to cutting agents found in heroin seizures. An application of graph theoretic methods has been performed, in order to highlight the possible relationships between the location of seizures and co-occurrences of particular heroin cutting agents. An analysis of the co-occurrences to establish several main combinations has been done. Results illustrate the practical potential of mathematical models in forensic data analysis.

Journal Article↗
PubMed2000

Molecular mimicry and the role of B lymphocytes in the processing of autoantigens.

The immune system has evolved several mechanisms that provide lymphocytes with the intelligence to ignore self proteins while attacking foreign pathogenic agents. Notably, B and T lymphocytes that encounter self antigen at either the inappropriate levels or affinity are usually instructed to perish or become anergized. However, the presence of autoimmune disease suggests that the induction of self tolerance is not foolproof. In fact, autoreactive cells are now found to be normal inhabitants of the B and T lymphocyte repertoire. This review examines how foreign peptides which resemble self proteins can elicit autoimmunity that is amplified to many sites on a target autoantigen. In particular, B lymphocytes initiated by foreign molecular mimics can process and present self peptides in the shaping of autoimmune T cell responses.

Animals↗
PubMed2006

Goal-based action selection and utility-based action bias.

According to artificial intelligence studies, goal-based and utility-based agents can select an action to attain a desired outcome. The goal-based agent sets a specific goal regardless of its utility at first, and selects the action that leads to that goal (goal-based action selection). The utility-based agent compares the utilities of different possible outcomes, and selects the action that causes the outcome with the highest utility (utility-based action bias). The medial prefrontal cortex is involved in implementing the goal-based action selection and the striatum is involved in implementing the utility-based action bias. Goal-based action selection may be temporarily dominant over the utility-based action bias in a new environment, whereas the utility-based action bias becomes dominant after acquisition of action utilities in the environment. This transition of dominance between the two decision systems may be enhanced by a reference-point shift based on the goal-setting process during goal-based action selection.

Animals↗
PubMed2000

Antipyretic Therapy's future.

There is little doubt that clinicians will continue to seek new and, one hopes, more intelligent ways to suppress fever. In the process, new agents will be developed, new uses will be identified for existing antipyretic agents, new measures will be designed to maximize the benefits of antipyretic therapy while minimizing its adverse effects, and a concerted effort will be made to define more clearly and to promote appropriate indications for such therapy.

Analgesics, Non-Narcotic↗