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Characterization of the receptor for heat-stable enterotoxin from Escherichia coli in rat intestine.

The receptor for the heat-stable enterotoxin (ST) from Escherichia coli was solubilized with Lubrol-PX from rat intestinal brush-border membranes and characterized. The binding kinetics and analog specificity of the solubilized receptor were virtually identical to those obtained with the membrane-bound receptor. Furthermore, the regulation of the receptor's affinity by cations was also maintained after solubilization, indicating a conservation of the toxin-binding site after removal of the receptor from its membrane environment. Gel filtration and sucrose density gradient sedimentation studies gave a Stokes radius of 5.5 nm and a sedimentation coefficient of 7.0 S for the solubilized receptor. The isoelectric point of the receptor was determined as 5.5 using Sephadex isoelectric focusing electrophoresis. In all of these separation techniques, the ST receptor showed a single peak of activity that was clearly separated from that of guanylate cyclase. When 125I-ST was cross-linked to brush-border membranes with disuccinimidyl suberate, the affinity-labeled receptor solubilized with 0.1% Lubrol-PX eluted at a similar position as the native receptor on gel filtration chromatography. Analysis of the affinity-labeled receptor by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of reducing agent and by autoradiography revealed the presence of three specifically labeled polypeptides with apparent molecular weights of 80,000, 68,000, and 60,000. These results suggest that the ST receptor is solubilized by Lubrol-PX in an active form with preservation of its regulation by cations. Also, the ST receptor is separable from particulate guanylate cyclase indicating that the receptor is coupled to the activation of guanylate cyclase by an as yet undefined mechanism. Three subunit peptides may constitute a binding region of the receptor.

Animals↗

[What differentiates and what connects psychotherapy and psychiatric somatotherapy? On the epistemology of therapeutic procedures].

In opposition to a dualistic conception of psychosomatic medicine which implies a determination of the psychical by the physical or vice versa we emphasize a circular relationship between a biological individuum on the one hand, comprising the psychical and the physical and its environment on the other. From this, every therapy appears as an interactional process between individuum and environment, the latter being represented by the respective therapeutic agent. Basing upon a biperspectivistic epistemology the following can be stated: In a case of psychiatric somatotherapy the therapeutic agent is of a physico-chemical, in the case of psychotherapy of a verbal-semantic or nonverbal-informative nature. Because psychiatric somatotherapy as well as psychotherapy is directed at a wholly individuum, comprising the psychical and the physical, one may postulate that any therapeutic effect is describable also from the two logically distinct but correlative points of view, the one corresponding to the psychical and the other to the physical. The virtual character of both kinds of therapy results from a different accentuation with respect to both the logically given perspectives. Concluding we try to specify differentially the possibilities and limitations inherent in psychiatric somatotherapy and in psychotherapy.

Adaptation, Psychological↗

Genotoxicity of industrial wastes and effluents.

In excess of several million pounds of genotoxic and/or carcinogenic industrial wastes are released into the U.S. environment each year. Chemical characterization of these waste materials can rarely provide an adequate assessment of their genotoxicity and potential hazard. Bioassays do not require prior information about chemical composition and can effectively assess the genotoxicity of complex waste materials. The most commonly used genotoxicity assay has been the Salmonella mutagenicity assay. Results with this system have shown that the genotoxic potency of industrial wastes can vary over 10 orders of magnitude, from virtually nondetectable to highly potent. Industries employing similar industrial processes generally release wastes of similar potency. Extremely high potency wastes include those from furazolidone and nitrofurfural production. Pulp and paper mills, steel foundries, and organic chemical manufacturing facilities also discharge wastes of noteworthy potency. Treatment and remediation of some wastes, such as pulp and paper mill effluents, have been shown to reduce or eliminate genotoxicity. However, in other cases, treatment and remediation have been shown to enhance genotoxicity, such as for fungal treatment of oils. Analyses of samples collected from areas known to receive industrial wastes and effluents have shown that genotoxins can accumulate in the receiving environment and have adverse effects on indigenous biota. The evaluation of hazardous wastes and effluents by genotoxicity assays may provide data useful not only for hazard identification but for comparative risk assessment.

Animals↗

Cosolvent-buffer mixtures as models for the cytoplasmic mileu: the enzymology of adenosine aminohydrolase.

Adenosine aminohydrolase from calf intestinal mucosa is sensitive to changes in its environment produced by small mole fractions of dimethylsulfoxide (DMSO). At a mole fraction of 0.1 where the dielectric constant is lowered from that of 78 of neat water to about 76.5, Vmax was reduced by 65% and affinity for substrate (adenosine) and the two competitive inhibitors, insine and N6-benzyladenosine, was decreased markedly. However, this decreased affinity was such that Ki/Km remained virtually constant for both inhibitors. DMSO itself showed the kinetics of a mixed inhibitor with Ki decreasing with increasing mole fraction. This cosolvent also decreased the heat stability of the enzyme which suggests that enzyme conformation is altered by DMSO. Comparison of data in the presence of DMSO with previously obtained data with dioxane shows that heat stability as well as Vmax, at a given value of dielectric constant, is independent of the amount or nature of cosolvent used to achieve that dielectric constant. However, cosolvent induced changes in Ki indicate that colligative as well as dielectric constant effects contribute to the observed changes in kinetic behavior. These experiments may be considered as models for the behavior of enzymes in the medium of lowered dielectric constant expected in the vicinity of cytoplasmic membranes. The results indicate that in such an environment, adenosine aminohydrolase would be expected to be less efficient a catalyst, but equally susceptible to product inhibition, as compared to media of dielectric constant approaching that of water.

Adenosine Deaminase↗

The environmental impact of diagnosis and therapy in obstructive sleep Apnea: A systematic review.

Healthcare contributes significantly to global greenhouse gas (GHG) emissions, yet the environmental impact of sleep medicine, particularly the diagnosis and therapy of obstructive sleep apnea (OSA), remains poorly characterized. We systematically searched PubMed, Scopus, and Embase (2015-2025) for studies on OSA care reporting environmental metrics (carbon footprint, energy use, resource consumption) or healthcare resource utilization. Supplementary searches identified additional non-peer-reviewed sustainability-focused studies that have been presented at conferences. Of 19 primary peer-reviewed studies on OSA care and utilization, only one reported environmental metrics (telemedicine CO2 savings related to reduction in travel-related emissions). Supplementary sources revealed that OSA care has a measurable carbon footprint driven by disposable equipment, device electricity, and travel and that OSA diagnostics create significant solid waste with opportunities for waste reduction through the use of reusable equipment. This review shows that while the environmental impact of sleep medicine has been rarely studied to this date, available evidence suggests significant opportunities for sustainability through virtual care, home testing, and equipment optimization. Future research should incorporate environmental impact into the assessment of clinical pathways.

Humans↗

The potential relevance of attachment theory in assessing relatedness with virtual humans.

Primary efforts to create virtual humans have been in the production of computer generated ergonomically correct objects that look like humans. Although there has been concern with essential human factors, absent are the metrics of human relatedness, or the ability to assess the degree to which a virtual human elicits human emotions. We discuss the potential application of attachment theory as a context for the development of such an assessment paradigm, and specifically the application of the Ainsworth Strange Situation in the evaluation of a "Virtual Mom". Virtual relatedness fidelity is discussed as a macrometric to define relatedness that would occur with virtual humans. Potential lessons learned are discussed as they apply to the selection of those to develop the model, and its impact on the introduction of virtual humans into clinical psychiatry and psychology.

Adult↗

Molecular mimicry in channel-protein structure.

The approach to probing the sequence-structure relationship of ion-channel proteins using small peptides stems from the abundance of sequence information and the virtual absence of structures at atomic resolution. It is anticipated that model peptides may fold predictably into stable structures and reproduce functional properties of specific proteins. Model peptides are well suited to the application of NMR methods to determine protein structure in a membrane environment or to high-resolution X-ray diffraction analysis. It is timely to ask what we have learned through this strategy and where it may lead in our quest to understand the sequence-structure determinism.

Amino Acid Sequence↗

Adhesion molecules on the plasma membrane of epidermal cells. III. Keratinocytes and Langerhans cells constitutively express the lymphocyte function-associated antigen 3.

It is now becoming clear that a collection of adhesion molecules is required on the surface of epidermal cells (EC) to establish the cell interactions that are necessary for skin immunologic reactions. In previous studies, we showed that human resting Langerhans cells (LC) express at least two members of the "integrins" family of adhesive molecules, as well as the intercellular adhesion molecule-1, which is a member of the immunoglobulin-related superfamily of molecules. This latter family includes another adhesive moiety, namely, the lymphocyte function-associated antigen-3 (LFA-3), which is the ligand for the T-lymphocyte-associated CD2 molecule, and has a broad tissue and organ distribution. In the present investigation the colloidal gold-immunoelectronmicroscopy immunostaining system and a quantitative analysis of the labeling provided decisive evidence for the weak but clear LFA-3 expression on virtually all keratinocytes (KC) and LC freshly isolated from normal human skin. Such constitutive expression of LFA-3 molecule on EC may be relevant for a number of functional interactions between LFA-3-positive EC and CD2-positive T lymphocytes within the cutaneous environment.

Antigens, Surface↗

Control of flea populations in a simulated home environment model using lufenuron, imidacloprid or fipronil.

Control strategies were evaluated over a 6-month period in a home simulation model comprising a series of similar carpeted pens, housing matched groups of six cats, in which the life-cycle of the flea Ctenocephalides felis felis Bouche (Siphonaptera: Pulicidae) had been established. Additional adult fleas were placed on the cats at intervals to mimic acquisition of extraneous fleas from outside the home. Treatment strategies included a single subcutaneous deposition of injectable lufenuron supported by initial treatments with a short-acting insecticidal spray, or monthly topical applications of imidacloprid or fipronil. An untreated control group indicated that conditions were suitable for flea replication and development. Controls had to be combed on 18 occasions to remove excessive flea burdens and two developed allergic reactions. Lufenuron cats were combed once and required two insecticidal treatments in the first month to achieve control. Even so, small flea burdens were constantly present thereafter. Imidacloprid and fipronil treatments appeared to give virtually complete control throughout. Single fleas were found on imidacloprid cats on two occasions, whereas none were recovered from fipronil cats at any time after the first treatment. Tracer cats were used to monitor re-infestation rates at the end of the trial period. Small numbers of host-seeking fleas were demonstrated in all treatment pens, indicating that total eradication had not been accomplished. It is concluded that the home environment simulation model incorporating tracer animals could provide a powerful tool for studying flea population dynamics under controlled conditions but improved techniques are needed for quantifying other off-host life-cycle stages.

Animals↗

Coevolution in variable mutualisms.

Many mutualistic interactions are probably not mutualistic across all populations and years. This article explores consequences of this observation with a series of genetic models that consider how variable mutualisms coevolve. The first models, previously introduced in a general coevolutionary context, consider two coevolving species whose fitness interactions change between beneficial and antagonistic in response to independent spatial or temporal variation in the abiotic or biotic environment. The results demonstrate that both temporal and spatial variability in fitness interactions can cause partner species with tightly matched traits favored by unconditional mutualisms to be vulnerable to evolutionary invasion by alternative types. A new model presented here shows that an additional mutualistic species can have a similar effect and can even cause fitness interactions between the other two species to evolve. Under some conditions, the pairwise interactions can change unidirectionally from mutualistic to antagonistic, with virtually no evolutionary change in either partner species. In other cases, fitness interactions between the species pair can oscillate between mutualism and antagonism as a result of coevolution in the third species. Taken as a whole, these theoretical results suggest that many features of mutualistic coevolution can best be understood by considering spatial, temporal, and community-dependent patterns of fitness interactions.

Biological Evolution↗

Emerging patterns in tumor systems: simulating the dynamics of multicellular clusters with an agent-based spatial agglomeration model.

Brain cancer cells invade early on surrounding parenchyma, which makes it impossible to surgically remove all tumor cells and thus significantly worsens the prognosis of the patient. Specific structural elements such as multicellular clusters have been seen in experimental settings to emerge within the invasive cell system and are believed to express the systems' guidance toward nutritive sites in a heterogeneous environment. Based on these observations, we developed a novel agent-based model of spatio-temporal search and agglomeration to investigate the dynamics of cell motility and aggregation with the assumption that tumors behave as complex dynamic self-organizing biosystems. In this model, virtual cells migrate because they are attracted by higher nutrient concentrations and to avoid overpopulated areas with high levels of toxic metabolites. A specific feature of our model is the capability of cells to search both globally and locally. This concept is applied to simulate cell-surface receptor-mediated information processing of tumor cells such that a cell searching for a more growth-permissive place "learns" the information content of a brain tissue region within a two-dimensional lattice in two stages, processing first the global and then the local input. In both stages, differences in microenvironment characteristics define distinctions in energy expenditure for a moving cell and thus influence cell migration, proliferation, agglomeration, and cell death. Numerical results of our model show a phase transition leading to the emergence of two distinct spatio-temporal patterns depending on the dominant search mechanism. If global search is dominant, the result is a small number of large clusters exhibiting rapid spatial expansion but shorter lifetime of the tumor system. By contrast, if local search is dominant, the trade-off is many small clusters with longer lifetime but much slower velocity of expansion. Furthermore, in the case of such dominant local search, the model reveals an expansive advantage for tumor cell populations with a lower nutrient-depletion rate. Important implications of these results for cancer research are discussed.

Algorithms↗

The effect of a history of conduct disorder in adult major depression.

This paper examines the impact of a history of conduct disorder on major depression in adulthood, including its symptomatology, comorbidity and response to tricyclic antidepressants. 103 subjects with DSM-III-R major depression were assessed for DSM-III-R axis I and II comorbidity, severity of depression, social functioning, general psychiatric symptomatology, early familial environment and family psychiatric history. 18 patients (17%) had a history of conduct disorder, 32 (31%) were subthreshold, and 53 (51%) had no childhood symptoms of conduct disorder. Depressed adults with a history of conduct disorder had significantly higher lifetime alcohol and drug dependence and virtually all (17/18, 94%) met criteria for a personality disorder. Despite this, the current episode of depression did not differ in severity, symptoms or response to treatment except that those with a history of conduct disorder were more likely to be agitated when depressed. The authors conclude that a history of conduct disorder is depressed patients predicts the presence of adult personality disorders and psychoactive substance dependence. In most other ways, depressed subjects with a history of conduct disorder were similar to other subjects.

Adolescent↗

The telecommunication revolution in the medical field: present applications and future perspective.

In the present review, we analyze the achievements of telecommunication innovations in the medical field focusing on patient care and medical-education aspects. In this regard, the telecommunication revolution has offered medical professionals the possibility to transmit information of any sort zeroing transmission time latency and annihilating spatial distances. Although telemedicine is still in its infancy, multiple applications of this science have already been successfully tested. As an example, robotically mediated telesurgery has it made possible for surgeons to operate standing at a considerable distance from the operating table without even touching or directly seeing the surgical field. Moreover, medical education and medical consulting have acquired new and wider ranges of applicability thanks to the introduction of teleproctoring, telementoring, and teleconsulting. Finally, in the very near future, telepresence surgery will permit "virtual" operations on patients where surgeons can project their manual dexterity, psychomotor skills, and problem-solving ability to remote locations. In this context, telemedicine will support a more equal distribution of medical knowledge and promote excellence in patients' care even in the most disadvantaged environments.

Humans↗

Technology-enhanced interactive surgical education.

BACKGROUND: Our goal was to create surgical resident centered, interactive teaching modules rich in basic science and clinical content directly pertinent to patient care and surgical techniques that would facilitate education in the 80-h work week environment. METHODS: A systematic evaluation of available instructional tools determined that a technology-enhanced approach can effectively and efficiently address the new requirements for resident learning. An extensive evaluation of available technology determined the technology best suited to teaching the adult surgical learner. RESULTS: An on-line, multimedia-based surgical education environment using WebCT Vista (WebCT, Inc., Lynnfield, MA) and Macromedia Breeze (Adobe Systems, Inc., San Jose, CA) software packages was implemented. The concept was constructed on tenets of adult learning theory and based on the APDS curriculum and ACGME core competencies. WebCT Vista serves as virtual scaffolding, and Macromedia Breeze functions to deliver content rich multimedia audio and visual presentations. Core subdiscipline teaching modules were created, comprised of individual lecture packets developed by faculty. Components for testing pre/post module knowledge, feedback and evaluations are built-in. The online nature allows for 24-h access at locations that are convenient to the resident. CONCLUSIONS: Teaching modules enable maximal trainee and instructor flexibility, which translates into optimal adult learning and teaching. Lecture packets can be conveyed to all residents with unlimited availability in the virtual domain. Further refinement and continued implementation will help fill the void in direct didactic teaching left by mandated work hour restrictions, allowing for more efficient learning and teaching. There is great potential for broad application of the concept and technology to other training programs.

Adult↗

Monitoring the species of arsenic, chromium and nickel in milled coal, bottom ash and fly ash from a pulverized coal-fired power plant in western Canada.

The concentration of As, Cr and Ni and their speciation (As3+;5+, Cr3+;6+ and Ni0;2+) in milled coal, bottom ash and ash collected by electrostatic precipitator (ESP) from a coal fired-power plant in western Canada were determined using HGAAS, ICP-AES and XANES. The chemical fractionation of these elements was also determined by a sequential leaching procedure, using deionized water, NH4OAC and HCI as extracting agents. The leachate was analyzed by ICP-AES. Arsenic in the milled coal is mostly associated with organic matter, and 67% of this arsenic is removed by ammonium acetate. This element is totally removed from milled coal after extraction with HCI. Arsenic occurs in both the As3+ and the As5+ oxidation states in the milled coal, while virtually all (>90%) of the arsenic in bottom ash and fly ash appears to be in the less toxic arsenate (As5+) form. Both Ni and Cr in the milled coal are extracted by HCI, indicating that water can mobilize Ni and Cr in an acidic environment. The chromium is leached by water from fly ash as a result of the high pH of the water, which is induced during the leaching. Ammonium acetate removes Ni from bottom ash through an ion exchange process. Chromium in milled coal is present entirely as Cr3+, which is an essential human trace nutrient. The Cr speciation in bottom ash is a more accentuated version of the milled coal and consists mostly of the Cr3+ species. Chromium in fly ash is mostly Cr3+, with significant contamination by stainless-steel from the installation itself.

Air Pollution↗

Fostering a culture of support in mental health settings: alternatives to traditional models of clinical supervision.

Clinical supervision [CS] for mental health nurses in inpatient settings in Sydney, Australia, is virtually nonexistent despite over a decade of discussion regarding its benefits to staff, patients, and organisations. Whilst there is general agreement about the merit of CS, its ad-hoc implementation and the use of models that do not correspond to the realities of the environment have led to its adoption being somewhat half-hearted. It is unsurprising then that there is an absence of achievable policy regarding CS making its integration into modern inpatient units even harder to attain. In this paper, we outline some pragmatic issues concerning CS and advocate for facility-specific professional development and support processes that incorporate succession planning opportunities. This we believe has the potential to promote professional behaviour, continuous learning and development, cohesive teamwork, and ultimately a change in culture regarding CS.

Culture↗

Circadian rhythms and time course of adaptive sodium and potassium excretion in rats after uninephrectomy.

The relationship between renal circadian cyclic excretion and renal compensatory adaptation after uninephrectomy for K, Na, and water was studied. Rats in a 12:12-h light-dark environment were given a liquid diet, and urine was collected for 16 days with consecutive 90-min periods. Days 1-4 were control, 5-10 followed a sham operation, and 11-16 followed uninephrectomy. The major findings were 1) the circadian cycles in excretion were virtually unchanged after sham and uninephrectomy; 2) an adaptive increase in excretion of Na, K, and water by the remaining kidney occurred within 90 min after uninephrectomy; 3) after uninephrectomy the distribution of the 24-h increment in excretion for the remaining kidney closely followed the preexisting pattern of circadian excretion for Na but was evenly distributed between light and dark phases for K; and 4) after uninephrectomy the ratio of excretion to intake was unchanged. This is the first study to document the time course of adaptation to uninephrectomy using consecutive brief collections over several days in unanesthetized and undisturbed rats. Adaptation after uninephrectomy occurred essentially immediately; was maintained unchanged; and preserved Na, K, and water homeostasis. Uninephrectomy did not alter the circadian control of excretion.

Animals↗

Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion.

Hindbrain norepinephrine (NE) and epinephrine (E) neurons play a pivotal role in the central distribution of sensory signals derived from the internal environment. Their projections influence the various secretory patterns of the hypothalamo-pituitary-adrenal axis and are essential for feeding and adrenal medullary responses to glucoprivation. NE and E terminals in the paraventricular nucleus of the hypothalamus (PVH) and associated hindbrain cell bodies can be virtually eliminated by PVH microinjection of a retrogradely transported conjugate of saporin (SAP, a ribosomal toxin) and a monoclonal antibody against dopamine beta-hydroxylase (dbetah), i.e. dbetah mouse monoclonal antibody conjugated to SAP (DSAP). To examine the effects of selective elimination of NE/E afferents on hypothalamo-pituitary-adrenal activation, we injected DSAP into the PVH and measured corticosterone secretion under basal circadian conditions and in response to two distinct challenges: glucoprivation and forced swim. DSAP lesions profoundly impaired glucoprivation-induced corticosterone secretion and induction of CRH heteronuclear RNA and Fos mRNA in the PVH, without impairing basal CRH mRNA expression, circadian corticosterone release, or the corticosterone response to swim stress. Thus, NE/E projections influence corticosterone secretion only in certain circumstances. They are required for the response to glucoprivation, but are dispensable for circadian activation and for the response to swim stress.

Animals↗