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PubMed2004

Dynamic force microscopy for imaging of viruses under physiological conditions.

Dynamic force microscopy (DFM) allows imaging of the structure and the assessment of the function of biological specimens in their physiological environment. In DFM, the cantilever is oscillated at a given frequency and touches the sample only at the end of its downward movement. Accordingly, the problem of lateral forces displacing or even destroying bio-molecules is virtually inexistent as the contact time and friction forces are reduced. Here, we describe the use of DFM in studies of human rhinovirus serotype 2 (HRV2) weakly adhering to mica surfaces. The capsid of HRV2 was reproducibly imaged without any displacement of the virus. Release of the genomic RNA from the virions was initiated by exposure to low pH buffer and snapshots of the extrusion process were obtained. In the following, the technical details of previous DFM investigations of HRV2 are summarized.

Journal Article↗

PubMed2005

Evaluation of an Interactive Case-based Online Network (ICON) in a problem based learning environment.

PURPOSE: This study sought to assess the introduction of a web-based innovation in medical education that complements traditional problem-based learning curricula. Utilizing the case method as its fundamental educational approach, the Interactive Case-based Online Network (ICON) allows students to interact with each other, faculty and a virtual patient in difficult neurological cases. Given the paucity of available metrics to benchmark online systems, we complement user perceptions with data on system utilization. METHODS: We describe a case study of distinct, small group tutorials over 2 years as part of the Human Nervous System and Behavior (HNSB) course at the Harvard Medical School. Participating students and faculty were interviewed following completion of the course and their utilization of the system was recorded and examined. RESULTS: Students each spent 3.2+/-1.3 h (mean+/-SD) through 8.6+/-2.8 accessions per week using ICON outside of required tutorial time. Faculty each spent 4.8+/-3.4 h through 16.6+/-8.9 accessions per week on ICON. Students identified real-time engagement, stronger relationships with faculty, increased accountability to the tutorial group and self-selected pace as the most beneficial characteristics of the ICON-based tutorial in comparison to traditional problem based learning (PBL) tutorials. Faculty identified enhanced collaboration with students and more realistic student experiences as the most beneficial characteristics. Both students and faculty reported that limitations of ICON included increased time investment for faculty and increased reliance on good faculty mentorship. CONCLUSION: This is the first study of the ICON learning system in undergraduate medical education, a platform designed to facilitate collaboration outside of the classroom. Data on user perceptions and system utilization suggest that both faculty and students chose to adopt this online learning system as a means for collaboration. The study also outlines future avenues for research in assessing novel online technologies.

Computers↗

PubMed2004

The concept of a clinical round as a virtual, interactive web-based, e-learning model for interdisciplinary teaching.

The demonstration of patient case reports in the course of a clinical round is an essential part of teaching medicine and dentistry. However, suitable live patients with particular problems are not always available at a time when teaching is taking place. This project therefore had the objective of establishing a web-based, virtual e-learning concept for demonstrating case reports independent of time and place, with the possibility of an interactive examination, diagnosis, and interdisciplinary therapy decision making for medical and dental students. Anonymized case reports of diseases in the oral and maxillofacial region and the interdisciplinary treatment were digitized and prepared in a web-based format. The technical aspect was based on connecting flash modules with videos and animation, and monitoring through HTML and Javascript. Due to the modular concept and the programming used, the learning environment was independent of platform and open. Independent formats (.swf, .avi, .mpeg, etc.) were integrated into the individual modules. According to a hierarchic decision system, the user was guided interactively to the diagnosis through a differential diagnostic exclusion process. Sound was digitized and integrated in mp3 compressed form in the 3D models for lip-synchronous speech output. The speech output was connected with a virtual 3D tutor that acted in an advisory capacity in reaching a diagnosis and determining therapy. Further sources of information and literature with abstracts or pdf files of the subject-related publications were inserted to ensure that the teaching was objective. To conclude the virtual clinical round, a check on learning success was conducted in the form of a multimedia multiple choice test.

Computer-Assisted Instruction↗

PubMed1987

Marijuana testing--how good is it?

Testing for the use of marijuana necessitates one or more levels of assessment, depending on the clinical application of the test results. The EMIT-dau screening test with a sensitivity limit of 20 ng/ml is highly satisfactory for screening for the absence of marijuana in the urine. This test has a virtual 100% true-negative rate as long as an unadulterated urine specimen is analyzed. Positive results by the EMIT-dau procedure are presumptive because the test seems to produce false-positive results when applied to a random population of suspected drug users. In a population in a specific clinical environment such as in drug-treatment programs in which 20 of every 100 specimens will yield positive THC-COOH results by EMIT-dau screening, 3 (15%) of the 20 positive results will likely be false-positive. Our experience with the EMIT-dau suggests that of 100 test results, 3 will be false-positive, an overall 3% false-positive rate. If a positive test result will put the patient in considerable jeopardy and the screening result is the only evidence of drug use, confirmatory testing is imperative. Of the confirmatory tests, GC/MS seems to have the specificity necessary to provide a high level of confidence in the results. A combination of the EMIT procedure with a sensitivity level of 20 ng/ml and GC/MS confirmation yields virtually 100% accuracy in detection of marijuana abuse.

Cannabinoids↗

PubMed2001

[The environment and autoimmunity--from external causes to inner conflicts].

Autoimmune disorders result from a breakdown of immunologic tolerance leading to an immune response against self-molecules. In most instances the events that initiate the immune response to self-molecules are unknown, but a number of studies suggest associations with environmental and genetic factors and certain types of infections. The concordance of autoimmune diseases among identical twins is virtually always less than 50%, often in the 25-40% range. This observation, as well as epidemic clustering of some autoimmune diseases following xenobiotic exposure, reinforces the thesis that autoimmune disease is secondary to both genetic and environmental factors. In addition, because of individual genetic susceptibilities based not only on major histocompatibility complex differences but also on differences in toxin metabolism, lifestyles, and exposure rates, individuals will react differently to the same chemicals. With these comments in mind it is important to note that there have been associations of a number of xenobiotics with human autoimmune disease, including mercury, iodine, vinyl chloride, canavanine, organic solvents, silica, L-tryptophan, particulates, ultraviolet radiation, and ozone. In addition, there is discussion in the literature that raises the possibility that xenobiotics may also exacerbate an existing autoimmune disorder. In this article these issues are discussed, in particular, the evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. With the worldwide deterioration of the environment, this is a particular important subject for human health. This is best illustrated by the epidemics of eosinophilic myalgia syndrome with shared characteristics that occurred about 20 years ago. Another example is the toxic oil syndrome of Spain in 1981 involving cooking oil led to both acute and chronic disease as well as formation of auto-antibodies to collagen, DNA, and skeletal muscle. Currently the question is risen whether there is a link between environmental estrogens and autoimmune disorders, especially since these illnesses are reported possibly more frequent. Yet for the time being, an answer is not available, since the current state of science with respect to autoimmunity and environmental agents is still in the early stages of hazard identification.

Autoantibodies↗

PubMed1993

Home-based and worksite-based exercise training for patients with coronary artery disease.

In the era of thrombolysis, exercise training for patients with ischemic heart disease should be reserved for enhancement of functional capacity and psychological well-being rather than improvement of prognosis. Low to moderate intensity exercise training enhances functional capacity to the same extent that group-based exercise training does and can be performed safely at home. The physical demands of occupational work have decreased to the point where patients with ischemic heart disease who manifest neither treadmill-induced myocardial ischemia nor left ventricular dysfunction can perform virtually any occupational task.

Ambulatory Care↗

PubMed2001

Genes and environment in type 2 diabetes and atherosclerosis in aboriginal Canadians.

The incidence of coronary heart disease (CHD) among aboriginal people in northern Ontario has tripled over the past 20 years. This is inextricably linked to the remarkably high prevalence of type 2 diabetes in these native communities. Approximately 40% of the Oji-Cree of northern Ontario have typical obesity-related type 2 diabetes, which represents a drastic increase from virtually unreportable levels 50 years ago. The Oji-Cree have a private mutation in the HNF1A gene, namely G319S, which is absent from other ethnic groups and aboriginal populations. The most compelling reasons that HNF1A S319 is a diabetes-susceptibility allele are its consistent statistical association with the presence and severity of diabetes. Also, HNF1A S319 has specificity and positive predictive values of 97% and 95%, respectively, for the development of diabetes in the Oji-Cree by 50 years of age. This makes the HNF1A G319S genotype the most specific predictive genetic test for diabetes in any human population. HNF1A S319 has all the attributes of a thrifty allele in the Oji-Cree. It is possible that the recent increase in CHD in the aboriginal people of northern Ontario is the result of the expression of diabetes susceptibility due to HNF1A S319 as a consequence of rapid changes in environment and lifestyle.

American Indian or Alaska Native↗

PubMed2004

The layers of presence: a bio-cultural approach to understanding presence in natural and mediated environments.

This paper proposes a bio-cultural theory of presence based on four different positions related to the role and structure of presence, as follows. First, presence is a defining feature of self and it is related to the evolution of a key feature of any central nervous system: the embedding of sensory-referred properties into an internal functional space. Without the emergence of the sense of presence it is impossible for the nervous system to experience distal attribution: the referencing of our perception to an external space beyond the limits of the sensory organs themselves. Second, even if the experience of the sense of presence is a unitary feeling, conceptually it can be divided in three different layers, phylogenetically different and strictly related to the three levels of self identified by Damasio. In particular we can make conceptual distinctions between proto presence (self vs. non self), core presence (self vs. present external world), and extended presence (self relative to present external world). Third, given that each layer of presence solves a particular facet of the internal/external world separation, it is characterized by specific properties. Finally, in humans the sense of presence is a direct function of these three layers: the more they are integrated, the more we are present. In the experience of optimal presence, biologically and culturally determined cognitive processes are working in harmony--to focus all levels of the self on a significant situation in the external world, whether this is real or virtual.

Animals↗

PubMed2005

Lithopanspermia in star-forming clusters.

This paper considers the lithopanspermia hypothesis in star-forming groups and clusters, where the chances of biological material spreading from one solar system to another is greatly enhanced (relative to action in the field) because of the close proximity of the systems and lower relative velocities. These effects more than compensate for the reduced time spent in such crowded environments. This paper uses approximately 300,000 Monte Carlo scattering calculations to determine the cross sections for rocks to be captured by binaries and provides fitting formulae for other applications. We assess the odds of transfer as a function of the ejection speed v (eject) and number N(.) of members in the birth aggregate. The odds of any given ejected meteoroid being recaptured by another solar system are relatively low, about 1:10(3)-10(6) over the expected range of ejection speeds and cluster sizes. Because the number of ejected rocks (with mass m > 10 kg) per system can be large, N (R) approximately 10(16), virtually all solar systems are likely to share rocky ejecta with all of the other solar systems in their birth cluster. The number of ejected rocks that carry living microorganisms is much smaller and less certain, but we estimate that N (B) approximately 10(7) rocks can be ejected from a biologically active solar system. For typical birth environments, the capture of life-bearing rocks is expected to occur N (bio) asymptotically equal to 10-16,000 times (per cluster), depending on the ejection speeds. Only a small fraction (f (imp) approximately 10(4)) of the captured rocks impact the surfaces of terrestrial planets, so that N (lps) asymptotically equal to 10(3)-1.6 lithopanspermia events are expected per cluster (under favorable conditions). Finally, we discuss the question of internal versus external seeding of clusters and the possibility of Earth seeding young clusters over its biologically active lifetime.

Astronomical Phenomena↗

PubMed2003

Loss of spatial learning in a patient with topographical disorientation in new environments.

The case is described of a patient who, following cerebral hypoxia, developed severe difficulty in orienting himself in new environments in the context of a mild global amnesic syndrome. Some episodes he related suggested that his main difficulty was remembering the spatial/directional value of landmarks he recognised. A neuroradiological examination documented severe bilateral atrophy of the hippocampi associated with atrophic changes in the cerebral hemispheres, most marked in the dorsal regions. Neuropsychological and experimental evaluation showed a severe deficit of spatial learning with substantially preserved ability to learn verbal and visual-object information. He was also virtually unable to learn a route in a maze task based exclusively on spatial data, but the availability of visual cues substantially improved his learning. Finally, he performed within normal limits on various tests investigating knowledge acquired premorbidly regarding famous buildings, routes in the town he had been living in since childhood, and geography. Topographical disorientation may be subtended by a specific difficulty in storing the spatial/directional value of visual landmarks in novel environments. The hippocampus appears to be involved in the acquisition of new topographical spatial knowledge.

Adult↗

PubMed2002

Human place learning in a virtual Morris water task: some important constraints on the flexibility of place navigation.

We investigated human place learning in a computerized version of the Morris water task (VMWT) under comparable conditions to those employed by Sutherland et al. (Sutherland et al. Psychobiology, 1987;15:48-57) with rats. Participants viewed a computer-generated environment and were trained to locate a hidden goal in one half of a circular pool (region 1). The opportunity to navigate in and view cues from region 2 was systematically varied during training. Participants were then started from region 2 to assess transfer. Accurate transfer performance was dependent upon prior experience viewing distal cues from region 2 while on a trajectory to the goal, a finding we interpret as inconsistent with the automatic formation and modification of a cognitive map (O'Keefe J, Nadel L. The Hippocampus as a cognitive map. Oxford, UK: Clarendon Press, 1978). Additionally, the transfer data reported here closely match the data obtained by Sutherland et al. with rats suggesting some generality in the principles involved in place learning.

Acoustic Stimulation↗

PubMed1999

Regulation of neural crest cell populations: occurrence, distribution and underlying mechanisms.

Regulation is a significant developmental event because successful cell proliferation and migration are critical to shaping young embryos. Regulation -- the replacement of undifferentiated embryonic cells by other cells in response to signals received from the environment -- is distinct from wound healing and regeneration. Investigations on regulation of neural crest cells span all vertebrates and have revealed that regulative ability varies both among classes (even species), and spatially and temporally within individuals. In general, there is greatest regulation for cranial neural crest cells, less for trunk, and virtually none forcardiac. Regulation also appears to be more complete at early embryonic stages. Fate-mapping studies have demonstrated that large regions of neural crest cells must be removed to generate missing or morphologically reduced structures. Recent studies reveal that less extensive neural crest cell extirpations result in normal morphology of cartilaginous and neuronal elements in the head, and normal development of pigmentation in the trunk. Ablation of cardiac neural crest cells frequently generates abnormalities of the heart, great vessels and parasympathetic nerve innervation. Decreased cell death, increased division, change in fate and altered migration are possible cellular mechanisms of regulation. In mostcases, the specific mechanisms of regulation are unknown, but a major premise underlying regulation is that cell potential is greater than cell fate. This concept was born from studies which demonstrated that some cells were able to express alternative fates if transplanted to a new environment. Among the potential cellular mechanisms for regulation, cell migration has received the most attention. Following ablation of neural crest cells, replacement neural crest cells migrate into gaps, most frequently from anterior/posterior locations. Cells from surrounding epidermal and neural ectoderm may have limited regulative ability, while compensation by cells from the ventral neural tube has been demonstrated to an even lesser extent. Regulation by such non-crest cells would require their transformation into neural crest cells. The potential for regulation of neural crest by placodal cells supports a closer relationship between neural crest and placodal ectoderm than previously recognized. Decreased cell death has been discussed primarily with reference to (1) cranial ganglia that have dual contributions from neural crest and placodal cells and (2) programmed cell death in rhombomeres three and five. Increased cell division in response to neural crest ablation is likely more common than has been reported, but this mechanism is difficult to interpret without a 3-D context for viewing how patterns of division differ from normal. Lastly, changes in cell fate may be the driving factor in regulation of embryonic cells. It has been repeatedly demonstrated thatcell potential is greaterthan cell fate. Once reliable mechanisms for assessing cell potential are established, we may find that fates are commonly altered in response to environmental signals. Regulation is therefore significant both as a basic developmental mechanism and as a mechanism for evolutionary change. The more labile the fate of embryonic cells, the more potential there is for maintaining existing characters and for generating new ones. According to Ettensohn (1992, p. 50), further analysis of such systems might < >. With regard to the neural crest, studies on regulation of this vital population of cells provide insight to the origin of the neural crest, to embryonic repair, and to the source of many craniofacial malformations, heart and other embryonic defects. (ABSTRACT TRUNCATED)

Animals↗

PubMed1996

Synthetic scleral reinforcement materials. II. Collagen types in the fibrous capsule.

Attainment of a steady state in fibrous-capsule formation around a polymeric implant is indicative of minimization of the foreign-body response, and is characterized by thin capsule walls, few macrophages, and the replacement of type III collagen with type I collagen within the capsular matrix. We implanted four general types of extraocular band materials (porous, solid, composite, and patched) in rabbit eyes, and examined the proportions of types III and I collagen in the surrounding fibrous-capsule walls at intervals after surgery. Immunohistochemical analysis showed that 18 months after implantation of the band materials, the capsules adjacent to the porous-material surfaces had virtually no type III collagen remaining, while the solid-surface-material capsules still contained more than trace amounts (greater than 5%). In that the bands were implanted around the outside of the globe, which provides a dynamic environment in constant motion, it may be that the cellular ingrowth permitted by the porous materials increased the stability of the implants, thereby lessening the foreign body response and allowing the collagen replacement characteristic of the steady state to be completed. In contrast the solid-surface implants, which had little cellular ingrowth, may have continued to undergo sufficient micromovement within the capsule walls to sustain a low-level activation of the wound-healing response, resulting in thicker capsule walls and residual type III collagen a year and a half after implantation surgery.

Animals↗

PubMed2007

Characterization of a BODIPY-labeled fluorescent fatty acid analogue. Binding to fatty acid-binding proteins, intracellular localization, and metabolism.

The BODIPY-labeled fatty acid analogues are a useful addition to the tools employed to study the cellular uptake and metabolism of lipids. In this study, we show that BODIPY FL C(16) binds to purified liver and intestinal fatty acid-binding proteins with high affinity at a site similar to that for the physiological fatty acid oleic acid. Further, in human intestinal Caco-2 cells BODIPY FL C(16) co-localizes extensively with mitochondria, endoplasmic reticulum/Golgi, and L-FABP. Virtually no esterification of BODIPY FL C(16) was observed under the experimental conditions employed. We conclude that BODIPY FL C(16) may be a useful tool for studying the distribution and function of FABPs in a cellular environment.

Boron Compounds↗

PubMed2004

Acquisition of typical EEG waveforms during fMRI: SSVEP, LRP, and frontal theta.

Recent work has demonstrated the feasibility of simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Virtually no systematic comparisons between EEG recorded inside and outside the MR scanner have been conducted, and it is unknown if different kinds of frequency mix, topography, and domain-specific processing are uniformly recordable within the scanner environment. The aim of the study was to investigate several typical EEG waveforms in the same subjects inside the magnet during fMRI and outside the MR examination room. We examined whether uniform artifact subtraction allows the extraction of these different EEG waveforms inside the scanner during EPI scanning to the same extent as outside the scanner. Three well-established experiments were conducted, eliciting steady state visual evoked potentials (SSVEP), lateralized readiness potentials (LRP), and frontal theta enhancement induced by mental addition. All waveforms could be extracted from the EEG recorded during fMRI. Substantially no differences in these waveforms of interest were found between gradient-switching and intermediate epochs during fMRI (only the SSVEP-experiment was designed for a comparison of gradient-with intermediate epochs), or between waveforms recorded inside the scanner during EPI scanning and outside the MR examination room (all experiments). However, non-specific amplitude differences were found between inside and outside recorded EEG at lateral electrodes, which were not in any interaction with the effects of interest. The source of these differences requires further exploration. The high concordance of activation patterns with published results demonstrates that EPI-images could be acquired during EEG recording without significant distortion.

Adult↗

PubMed2004

Learning effect of a novel interactive basic life support CD: the JUST system.

INTRODUCTION: Electronic interactive learning environments can enhance the learning experience and may prove beneficial in basic life support (BLS) training. As part of the European Union funded project "JUST-in-time health emergency interventions-training of non-professionals by virtual reality and advanced IT tools", an innovative interactive CD-ROM on BLS and other emergency medicine topics was developed. We hypothesised that individuals without previous BLS training could learn CPR techniques from this CD. METHODS: Sixty-two students were randomised into a group studying the JUST CD in a computer class room for up to 60 min, and a control group who did not receive any training (serving as a reference). CD users also completed a satisfaction questionnaire immediately after studying the CD. The BLS skills of both groups were assessed in a mock BLS scenario on a training manikin. BLS performance was video recorded and analysed. RESULTS: After studying the CD for a mean period of 42 min, users of the CD had better assessment skills and were more likely to show a positive helping attitude, but chest compression and breathing techniques were ineffective. Most users rated the CD as very good and a positive learning tool. CONCLUSION: Individuals without prior BLS training showed improved behaviour and assessment skills after exposure to the CD, but motor skill acquisition requires alternative learning strategies.

CD-ROM↗

PubMed2002

4.1 Web-based interactive learning programmes.

In the future, the training of competent dentists will need to take advantage of up-to-date digital technologies and learning practices. In order to accomplish this, the following goals should be considered: i) the design of 'customizable' web-based curriculum matrices that accommodate the training philosophies and resources of individual dental schools; ii) the development of digital instructional modules that can be incorporated or downloaded into specific parts of a curriculum; iii) the establishment of an e-consortium, which provides peer view and guidance in the design of teaching modules, and which is responsible for the storage, maintenance, and distribution of teaching modules within the consortium; iv) the development of central human and physical resources at each dental school to enable the seamless delivery of instructional modules in a variety of learning environments; and v) the assessment and provision of ICT training to students and faculty with respect to the use of computers and related digital technologies and educational software programmes. These goals should lead to the creation of a 'virtual dental school'. Within this project summative and formative evaluations should be performed during both the production and development of teaching material (e-learning material) and the learning process. During the learning process the following aspects should be measured and evaluated: i) students' behaviour; and ii) effectiveness, retention and the transfer of e-learned material into the clinical situation. To obtain evidence of the efficacy of e-learning material a certain amount of research has to be done in the near future. It is suggested that all parameters currently known have to be implemented during the development of a learning programme. Previous workers have evaluated the following elements with e-learning: i) planning, ii) programming and technical development, iii) learning behaviours, iv) learning outcomes of both the programme and the student, v) the acquisition of knowledge, skills and attitude and vi) the transfer of e-learned skills into clinical situations.

Competency-Based Education↗

PubMed1998

Preferential adhesion of prostate cancer cells to a human bone marrow endothelial cell line.

BACKGROUND: In virtually all patients with advanced prostate cancer, the disease metastasizes to bone and causes osteoblastic growth. However, the mechanisms that contribute to bone metastasis are poorly understood. It has been hypothesized that the bone provides a favorable growth environment for prostate cancer cells, which nonselectively seed the bone marrow from the bloodstream. Alternatively, prostate cancer cells may preferentially bind to bone marrow endothelial cells. We developed an in vitro model of bone endothelium and tested the hypothesis that prostate cancer cells adhere preferentially to bone marrow endothelial cells. METHODS: We isolated and characterized a human bone marrow endothelial (HBME-1) cell line. Cells were transfected with the simian virus 40 large T antigen for immortalization. Cell surface receptors were characterized by immunohistochemistry and flow cytometry. The adhesion of cancer cells to HBME-1 and to endothelial cell lines from other organs was tested in an in vitro binding assay as were inhibitors of adhesion. RESULTS: The immortalized HBME-1 cell line demonstrated many properties characteristic of endothelial cells, including positive staining for von Willibrand factor and rapid formation of tubule structures when exposed to extracellular matrices. In an in vitro assay, prostate cancer cells adhered preferentially to human bone marrow endothelium when compared with endothelium derived from other sources. Preferential adhesion was blocked, in part, by antibodies to galectin-3 and LFA-1. IMPLICATIONS: These data suggest that the propensity of prostate cancer cells to establish themselves in bone is due, at least in part, to their preferential adhesion to human bone marrow endothelial cells.

Bone Marrow Cells↗