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Effect of cyclic loading and environmental aging on the fracture toughness of dental resin composite.

OBJECTIVE: The main purpose of this study was (1) to investigate the effects of cyclic loading and environmental aging on three dental resin composites with different filler compositions: a fiber filler, a hybrid filler, and a microfill; and (2) to predict fracture in dental resin composite under mixed-mode loading conditions. METHODS: Diametral disk specimens 25 mm in diameter and 2 mm in thickness were used in this study. Two methods were used for generating initial cracks in the specimen. The first method involved machining a 3-mm notch in the center of the disk specimens, and then the notch tips were sharpened with a 0.2-mm-diameter jeweler's saw blade. In the second method for obtaining sharper crack tips, a three-way wedge was forced into a 3.175-mm hole drilled in the center of the specimen, resulting in sharp cracks emanating from the notch tips. CYCLIC TESTS: The specimens were aged for 4 months in air, water, artificial saliva, and a 50/50 (by volume) mixture of ethanol and water at room temperature in sealed polyethylene containers. Both unaged and aged specimens (5 specimens for each variable) were subjected to cyclic loading at a frequency of 5 Hz with sinusoidal loads cycling for 1, 1000, and 100,000 cycles at a load level approximately 60% of the fracture load for noncycled specimens. Following load cycling, the specimens were tested in compression in a displacement-controlled loading mode at a loading rate of 1.27 mm/min. RESULTS: Test results show that aging in a 50/50 alcohol-water mixture lowered the fracture toughness of dental resin composite, which was further reduced by cyclic loading. MIXED-MODE TESTS: The maximum tensile stress (MTS) criterion was used to predict fracture in dental resin composite under mixed-mode loading conditions. The loads at failure were used as input into a finite element model. After obtaining the stress field in the specimens by the finite element method, the mixed-mode stress intensity factors were calculated using an interaction energy integral method. RESULTS: Good agreement was obtained between the fracture envelope predicted by the MTS criterion and the experimental fracture toughness data. Hence, it can be concluded that it is only necessary to characterize the mode I fracture toughness to fully characterize the mixed-mode behavior of the dental resin composites that were considered in the present study.

Composite Resins↗

Development of the supraorbital and mandibular lateral line canals in the cichlid, Archocentrus nigrofasciatus.

The development of two of the cranial lateral line canals is described in the cichlid, Archocentrus nigrofasciatus. Four stages of canal morphogenesis are defined based on histological analysis of the supraorbital and mandibular canals. "Canal enclosure" and "canal ossification" are defined as two discrete stages in lateral line canal development, which differ in duration, an observation that has interesting implications for the ontogeny of lateral line function. Canal diameter in the vicinity of individual neuromasts begins to increase before ossification of the canal roof in each canal segment; this increase in canal diameter is accompanied by an increase in canal neuromast size. The mandibular canal generally develops later than the supraorbital canal in this species, but in both of these canals development of the different canal segments contained within a single dermal bone is asynchronous. These observations suggest that a dynamic process requiring integration and interaction among different tissues, in both space and time, underlies the development of the cranial lateral line canal system. The supraorbital and mandibular canals appear to demonstrate a "one-component" pattern of development in Archocentrus nigrofasciatus, where the walls of each canal segment grow up from the underlying dermal bone and then fuse to form the bony canal roof. This is contrary to numerous published reports that describe a "two-component" pattern of development in teleosts where the bony canal ossifies separately and then fuses with an underlying dermal bone. A survey of the literature in which lateral line canal development is described using histological analysis suggests that the occurrence of two different patterns of canal morphogenesis ("one-component" and "two-component") may be due to phylogenetic variation in the pattern of the development of the lateral line canals.

Animals↗

A stochastic model of cell replicative senescence based on telomere shortening, oxidative stress, and somatic mutations in nuclear and mitochondrial DNA.

Human diploid fibroblast cells can divide for only a limited number of times in vitro, a phenomenon known as replicative senescence or the Hayflick limit. Variability in doubling potential is observed within a clone of cells, and between two sister cells arising from a single mitotic division. This strongly suggests that the process by which cells become senescent is intrinsically stochastic. Among the various biochemical mechanisms that have been proposed to explain replicative senescence, particular interest has been focussed on the role of telomere reduction. In the absence of telomerase--an enzyme switched off in normal diploid fibro-blasts-cells lose telomeric DNA at each cell division. According to the telomere hypothesis of cell senescence, cells eventually reach a critically short telomere length and cell cycle arrest follows. In support of this concept, forced expression of telomerase in normal fibroblasts appears to prevent cell senescence. Nevertheless, the telomere hypothesis in its basic form has some difficulty in explaining the marked stochastic variations seen in the replicative lifespans of individual cells within a culture, and there is strong empirical and theoretical support for the concept that other kinds of damage may contribute to cellular ageing. We describe a stochastic network model of cell senescence in which a primary role is played by telomere reduction but in which other mechanisms (oxidative stress linked particularly to mitochondrial damage, and nuclear somatic mutations) also contribute. The model gives simulation results that are in good agreement with published data on intra-clonal variability in cell doubling potential and permits an analysis of how the various elements of the stochastic network interact. Such integrative models may aid in developing new experimental approaches aimed at unravelling the intrinsic complexity of the mechanisms contributing to human cell ageing.

Cell Culture Techniques↗

Anatomy of the ocellar interneurons of acridid grasshoppers. II. The small interneurons.

The anatomy of the small ocellar interneurons in the brain of the acridid grasshopper Schistocerca vaga was revealed by cobalt-filling the three ocellar nerves and subsequent reconstructions from silver-intensified (Timm's method) serial sections. In total, 61 small ocellar interneurons were repeatedly identified with arborizations in many areas of the brain and optic lobe, including in particular the posterior neuropil, ocellar tracts, protocerebral bridge, lobula, ventral bridge and tritocerebral crotch, calyces, and antenno-glomerular tracts. Each ocellar nerve contains the axons of small cells that arborize in the other two ocellar tracts; these tracts are sites of ocellar integration. Direct interactions between the ocelli and compound eyes are suggested by the projections of small ocellar interneurons into the proximal lobula. Small cell arborizations from all three ocelli are distributed actoss much of the protocerebral bridge, implying a role for the bridge as an ocellar neuropil within the brain. Four of the small interneurons could be seen in whole-mount preparations and are demonstrated to be identical in five species of acridid grasshoppers of two different subfamilies: Schistocera vaga, S. gregaria, Gastrimargus africanus, Trimerotropis pallidipennis, and Arphia conspersa.

Animals↗

Ion channel are sensitive to gravity changes.

The effects of gravity on alamethicin doped planar lipid bilayers and on reconstituted porins of Escherichia coli outer membrane, respectively, have been investigated in this paper. The aim of the study was to find out whether and how gravity influences the highly stratified system: membrane-ion channel, in order to provide a novel approach to the explanation of gravity effects on living systems. This is necessary, as even single cells can react to gravity changes without having perceptive organelles. The mechanism of this detection is not clear yet. One possibility might be the detection of gravity by the membrane itself, or by the interaction of integral membrane proteins with gravity. Here we show for the first time that gravity directly influences the integral open state probability of native ion channels (porins) incorporated into planar lipid bilayers. Under hypergravity, especially the open state probability of porins is increased, whereas it is decreased in the microgravity case. The dependency is sigmoidal with the steepest region at 1 to 1.3 g. In the light of these experiments, a general effect of gravity on ion channels and membranes seems to be reasonable, possibly providing an explanation for several impacts of gravity on living systems.

Alamethicin↗

[Pain syndromes with causal participation of the sympathetic nervous system].

The efferent sympathetic nervous system is organized into subsystems that innervate and regulate via separate peripheral sympathic pathways the different autonomic target organs. This review discusses mechanisms through which this efferent system may be causally involved in the generation of pain. Clinical pain syndromes in which this may be the case are "complex regional pain syndromes" (CRPS) type I (previously reflex sympathetic dystrophy) and type II (recently causalgia). The "sympathetically maintained pain" (SMP) is a symptom (and not a clinical entity) that can principally also be present in other pain syndromes. An explanatory hypothesis, which may explain the clinical phenomenology of CRPS (different types of pain, swelling, autonomic, motor and trophic changes) and the mechanisms involved, is described and discussed. This hypothesis consists of different components that either have been tested and verified experimentally or which are still hypothetical. The hypothesis consists of changes in the primary afferent (nociceptive and non-nociceptive) neurones (sensitization, ectopic impulse generation) and of the neurones in the spinal cord (preferentially in the dorsal horn) which are secondary consequences of the changes in the primary afferent neurones ("central sensitization"). These changes are not specific for SMP. The centerpiece of the hypothesis is a positive feedback circuit that consists of the primary afferent neurones, spinal cord neurones, sympathic neurones and the pathologic sympathetic-afferent coupling. This coupling can occur directly via noradrenaline (or possibly another substance) at different sites of the afferent neurone (at the lesion site, remote from the lesion site in the periphery and in the spinal ganglion). The direct coupling requires that the afferent neurone expresses adrenoceptors. Indirect coupling can occur via the vascular bed or otherwise, e.g. by changes of the neurovascular transmission. The activity in the sympathetic neurones to the affected extremity can change. This change does not consist of a generalized increase of sympathetic activity but of a change of the reflexes (e.g., thermoregulatory and nociceptive reflexes). From this follows that the pathophysiologal processes operating in CRPS may occur at four levels of integration that interact with each other: effector organ, peripheral afferent and sympathetic neurone, spinal cord, supraspinal centres. Recent experimental investigations on rats show that the sympathetic nervous system is possibly also causally involved in the generation of inflammation and inflammatory pain. The mechanisms by which this occurs are different from those operating in SMP during CRPS.

Animals↗

Which role can arbuscular mycorrhizal fungi play in the facilitation of Ambrosia artemisiifolia L. invasion in France?

Ambrosia artemisiifolia L. (common ragweed), an annual invasive plant, was introduced more than 100 years ago from North America to Europe. Like the majority of other invasive plants in Europe, it develops in open, disturbed areas such as fields, wastelands, roadsides, and riverbanks. Recently, arbuscular mycorrhizal fungi (AMF) have been suspected to play a role in some plant invasion processes. As the common ragweed is known to be colonized by AMF in its native range, the intensity of mycorrhizal root colonization was studied in 35 natural populations in eastern France. About 94% of the A. artemisiifolia populations sampled were mycorrhizal. Root colonization levels varied from 1 to 40% depending on the ecological sites, with lower levels for agricultural habitats and higher levels in disturbed sites, such as wastelands or roadsides. A subsequent greenhouse experiment showed positive impacts of AMF on the growth and development of A. artemisiifolia. It is proposed that the spread of this invasive plant species could be facilitated by AMF, underlining the need to integrate symbiotic interactions in future work on invasive plant processes.

Ambrosia↗

Strategies to design pyrazolyl urea derivatives for p38 kinase inhibition: a molecular modeling study.

The p38 protein kinase is a serine-threonine mitogen activated protein kinase, which plays an important role in inflammation and arthritis. A combined study of 3D-QSAR and molecular docking has been undertaken to explore the structural insights of pyrazolyl urea p38 kinase inhibitors. The 3D-QSAR studies involved comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The best CoMFA model was derived from the atom fit alignment with a cross-validated r (2 )(q (2)) value of 0.516 and conventional r (2) of 0.950, while the best CoMSIA model yielded a q (2) of 0.455 and r (2) of 0.979 (39 molecules in training set, 9 molecules in test set). The CoMFA and CoMSIA contour maps generated from these models provided inklings about the influence of interactive molecular fields in the space on the activity. GOLD, Sybyl (FlexX) and AutoDock docking protocols were exercised to explore the protein-inhibitor interactions. The integration of 3D-QSAR and molecular docking has proffered essential structural features of pyrazolyl urea inhibitors and also strategies to design new potent analogues with enhanced activity.

Drug Design↗

Oral absorption enhancement of cromolyn sodium through noncovalent complexation.

PURPOSE: To determine the effect of Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on the permeation of cromolyn across Caco-2 cell monolayers and explore the molecular basis for the enhanced absorption. METHODS: Transport studies of cromolyn across Caco-2 cell monolayers were conducted in the presence of various SNAC concentrations. Permeation of cellular transport markers and lactate dehydrogenase (LDH) release were measured to evaluate cell integrity. Molecular interactions betweent the two compounds were investigated using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR), and Fourier-transfrom infrared (FTIR) spectroscopies and molecular dynamics simulations. RESULTS: The absorption of cromolyn across Caco-2 monolayers was enhanced markedly by SNAC. SNAC did not cause significant LDH leakage and changes in the permeation of transport markers. ITC, spectroscopies, and molecular dynamic simulations indicated the existence of intermolecular interactions between cromolyn and SNAC that involve the 2-hydroxybenzamide moiety on SNAC and weaken the hydrogen bonding between cromolyn and surrounding water molecules. CONCLUSIONS: SNAC increases the permeability of Caco-2 monolayers to cromolyn without measurable cell damage. SNAC interacts with cromolyn mainly via ring stacking. One major mode of interaction appears to involve the insertion of the aromatic ring of SNAC between cromolyn's rings. Such interaction appears to reduce the hydration of cromolyn and thus optimize its hydrophobicity for oral absorption.

Absorption↗

Long-term potentiation as synaptic dialogue.

We have proposed a testable model of the physiological and biochemical events underlying LTP that offers the following novel features. (1) The focus is not on a single mechanism or synaptic site, but rather on the integration and interaction of mechanisms occurring on both sides of the synapse, (2) beta PKC plays a critical presynaptic role in LTP, while gamma PKC functions postsynaptically. (3) These stages can be ordered in a time-delimited sequence of post- then presynaptic molecular events based on the period of effectiveness of inhibitor compounds. (4) The distinction is made between the time when kinase activation occurs and the time when the potentiated response requiring this kinase activation is observed.

Animals↗

The alpha-helix to beta-sheet transition in poly(L-lysine): effects of anesthetics and high pressure.

Poly(L-lysine) exists in a random-coil formation at a low pH, alpha-helix at a pH above 10.6, and transforms into beta-sheet when the alpha-helix polylysine is heated. Each conformation is clearly distinguishable in the amide-I band of the infrared spectrum. The thermotropic alpha-to-beta transition was studied by using differential scanning calorimetry. At pH 10.6, the transition temperature was 43.5 degrees C and the transition enthalpy was 170 cal/mol residue. At pH 11.85, the measurements were 36.7 degrees C and 910 cal/mol residue, respectively. Volatile anesthetics (chloroform, halothane, isoflurane and enflurane) partially transformed alpha-helix polylysine into beta-sheet. The transformation was reversed by the application of hydrostatic pressure in the range of 100-350 atm. Apparently, the alpha-to-beta transition was induced by anesthetics through partial dehydration of the peptide side-chains (beta-sheet surface is less hydrated than alpha-helix). High pressure reversed this process by re-hydrating the peptide. Because the membrane spanning domains of channel and receptor proteins are predominantly in the alpha-helix conformation, anesthetics may suppress the activity of excitable cells by transforming them into a less than optimal structure for electrogenic ion transport and neurotransmission. Proteins and lipid membranes maintain their structural integrity by interaction with water. That which attenuates the interaction will destabilize the structure. These data suggest that anesthetics alter macromolecular conformations essentially by a solvent effect, thereby destroying the solvation water shell surrounding macromolecules.

Anesthetics↗

Excision and integration of a self-transmissible replicon of Streptomyces ambofaciens.

When Streptomyces ambofaciens OSF was crossed with the plasmid-free Streptomyces lividans TK24, almost all S. lividans exconjugants contained the free 11.1-kb plasmid pOS1. Southern hybridizations showed that pOS1 was derived from the integrated copy of previously recognized plasmid pSAM2 present in strain OSF. A shorter derivative of pOS1 was constructed carrying the tsr gene in a non-essential region, and this pOS7 plasmid was used in transformation experiments with protoplasts of S. ambofaciens ATCC23877 (containing pSAM2 only as an integrated sequence) and S. ambofaciens DSM40697 (devoid of pSAM2-related forms). In both cases, some clones carrying pOS7 in an integrated state were found. Integration into strain ATCC23877 was into the pre-existing integrated copy of pSAM2. In contrast, plasmid pOS7 integrated through specific plasmidic and chromosomal sites into strain DSM40697. Thus it is probable that pSAM2 integrates by interaction between preferred regions of the plasmid and host genomes.

Animals↗

Altered responsiveness to alcohol after exposure to organic lead.

Ethyl alcohol is known to effect the functional integrity of the limbic system, particularly the hippocampus, and to alter behaviors which are thought to be mediated through limbic function. Organometals also compromise the limbic system and result in deficits in learning and memory. Since both alcohol and organoleads are present in the environment and seem to influence limbic integration, the interaction of these two compounds was assessed in the present experiment. Thirty male rats of the Fischer-344 strain were divided into three equal groups and were given injections of trimethyl lead (TML) (8.0 or 17.0 mg/kg/ml SC) or the saline vehicle. Fourteen days later, all animals were challenged with a single hypnotic dose of ethanol (3.5 g/kg IP). The 20% v/v solution of alcohol was prepared in water from a stock solution of 95% ethanol. The latency to loss of the righting reflex and duration of sleep time were recorded while the rats were kept in sound-attenuating chambers. The rats treated with the highest dose of TML manifested significantly longer latencies to lose the righting reflex and shorter durations of sleep than did controls. These results suggest that exposure to environmental lead may alter the biological and behavioral responsiveness of an animal to alcohol.

Animals↗

An online interactive simulation system for medical imaging education.

This report presents a recently developed web-based medical imaging simulation system for teaching students or other trainees who plan to work in the medical imaging field. The increased importance of computer and information technology widely applied to different imaging techniques in clinics and medical research necessitates a comprehensive medical imaging education program. A complete tutorial of simulations introducing popular imaging modalities, such as X-ray, MRI, CT, ultrasound and PET, forms an essential component of such an education. Internet technologies provide a vehicle to carry medical imaging education online. There exist a number of internet-based medical imaging hyper-books or online documentations. However, there are few providing interactive computational simulations. We focus on delivering knowledge of the physical principles and engineering implementation of medical imaging techniques through an interactive website environment. The online medical imaging simulation system presented in this report outlines basic principles underlying different imaging techniques and image processing algorithms and offers trainees an interactive virtual laboratory. For education purposes, this system aims to provide general understanding of each imaging modality with comprehensive explanations, ample illustrations and copious references as its thrust, rather than complex physics or detailed math. This report specifically describes the development of the tutorial for commonly used medical imaging modalities. An internet-accessible interface is used to simulate various imaging algorithms with user-adjustable parameters. The tutorial is under the MATLAB Web Server environment. Macromedia Director MX is used to develop interactive animations integrating theory with graphic-oriented simulations. HTML and JavaScript are used to enable a user to explore these modules online in a web browser. Numerous multiple choice questions, links and references for advanced study are provided in the tutorial for trainees to verify their understanding of each unit. It is expected that this tutorial will enhance medical imaging education, help trainees in subsequent analysis of image data, and form the basis for the development of more advanced technologies in the future.

Computer Simulation↗

Ubiquitous computing to support co-located clinical teams: using the semiotics of physical objects in system design.

OBJECTIVES: Co-located teams often use material objects to communicate messages in collaboration. Modern desktop computing systems with abstract graphical user interface (GUIs) fail to support this material dimension of inter-personal communication. The aim of this study is to investigate how tangible user interfaces can be used in computer systems to better support collaborative routines among co-located clinical teams. METHODS: The semiotics of physical objects used in team collaboration was analyzed from data collected during 1 month of observations at an emergency room. The resulting set of communication patterns was used as a framework when designing an experimental system. Following the principles of augmented reality, physical objects were mapped into a physical user interface with the goal of maintaining the symbolic value of those objects. RESULTS: NOSTOS is an experimental ubiquitous computing environment that takes advantage of interaction devices integrated into the traditional clinical environment, including digital pens, walk-up displays, and a digital desk. The design uses familiar workplace tools to function as user interfaces to the computer in order to exploit established cognitive and collaborative routines. CONCLUSION: Paper-based tangible user interfaces and digital desks are promising technologies for co-located clinical teams. A key issue that needs to be solved before employing such solutions in practice is associated with limited feedback from the passive paper interfaces.

Computer Peripherals↗

How do we selectively activate skin nociceptors with a high power infrared laser? Physiology and biophysics of laser stimulation.

This review presents and discusses the leading arguments justifying the use of high power laser stimulators to explore the nociceptive system. To grasp the particularity of such stimulators, fundamentals concerning the interaction of low-energy radiation with the skin will be recalled and focused on the optimal match between the wavelength of the emitting source and the thermophysical properties of the skin. This knowledge shall allow us to discuss critical characteristics of laser stimulators. Study of the cutaneous spectrum of receptors showed that laser stimulators allow the selective activation of A(delta) and C-fiber nociceptors. We will present different methods, which increase the selectivity of the laser stimulation, restricting the activation to isolated C-fiber nociceptors. These methods open new perspectives in the study of the cerebral processing of signals ascending through A(delta) and/or C nociceptors and should contribute to a better understanding of their central interaction and integration in normal and pathological states.

Biophysical Phenomena↗

Dexras1 potentiates photic and suppresses nonphotic responses of the circadian clock.

Circadian rhythms of physiology and behavior are generated by biological clocks that are synchronized to the cyclic environment by photic or nonphotic cues. The interactions and integration of various entrainment pathways to the clock are poorly understood. Here, we show that the Ras-like G protein Dexras1 is a critical modulator of the responsiveness of the master clock to photic and nonphotic inputs. Genetic deletion of Dexras1 reduces photic entrainment by eliminating a pertussis-sensitive circadian response to NMDA. Mechanistically, Dexras1 couples NMDA and light input to Gi/o and ERK activation. In addition, the mutation greatly potentiates nonphotic responses to neuropeptide Y and unmasks a nonphotic response to arousal. Thus, Dexras1 modulates the responses of the master clock to photic and nonphotic stimuli in opposite directions. These results identify a signaling molecule that serves as a differential modulator of the gated photic and nonphotic input pathways to the circadian timekeeping system.

Animals↗

Biomechanical assessment and treatment in lower extremity prosthetics and orthotics: a clinical perspective.

Biomechanical treatment is like a jigsaw puzzle with two complex counterparts having many pieces. The physical and mechanical components are equally important and cannot be separated from each other. The patient with a prosthesis or an orthosis represents a biomechanical system; total treatment is essential. All of the pieces to the puzzle must be used to complete the picture. Given the present structure of the educational system, there is a separation of disciplines necessary to provide one truly biomechanical treatment. Physical therapists are educated in the bio aspect of treatment, whereas prosthetists/orthotists are educated in the mechanical aspect. Biomechanical treatment requires the direct interaction and integration of the two disciplines. Physical therapists and prosthetists/orthotists need each other. One without the other can provide only half of the treatment necessary for optimal outcomes. The patient needs both. Physical therapists need to become more familiar with mechanical treatment and learn how to integrate this into their physical treatment program. Prosthetists/orthotists must become more familiar with the importance of physical treatment and the internal corrective forces necessary for efficient ambulation. The traditional label of orthotics and prosthetics and related technology as products must be replaced with biomechanical treatment that includes orthotics and prosthetics services. Professionals working with each other is a positive step, but they need to be working together as a team toward a common goal. They need to be in the same place at the same time and work together consistently to provide total treatment. This is more than a multidisciplinary approach. It is one treatment. In this way, each benefits the other as they teach and learn simultaneously. At present, this teaching and learning can be done only on an individual basis. It is the author's hope that experienced prosthetists/orthotists and physical therapists reading this article will see the need to combine their efforts to provide truly biomechanical treatment. By working together, they can expand their present knowledge and skills. In this way, treatment and outcomes can improve and serve as the guiding force for a new generation of rehabilitation specialists. This process can be expedited through the educational system by offering advanced clinical degrees specializing in biomechanical treatment specifically designed for clinical practice rather than research, administrative, or academic positions. For this idea to become reality, educational institutions representing the physical and mechanical aspects of biomechanical treatment also must work together; this would expedite the learning curve so that it would not take so long to put the pieces of the puzzle together.

Amputation, Surgical↗