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PubMed1995

Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT.

Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

Animals↗

PubMed2005

An exploration of nurse-patient relationships in accident and emergency.

This paper explores the nature of nurse-patient relationships in accident and emergency (A&E) drawing from nursing theory and research, and with reflection on three episodes of practice from the author's experience. First the case for nurse-patient relationships is presented with reference to nursing theory, statutory and professional literature. The benefits of positive nurse-patient relationships in A&E are then explored, followed by a discussion of the barriers to nurse-patient relationships forming in A&E. How relationships are formed is then considered, highlighting the short space of time available, and the importance of first impressions. The first practice episode analysed is a situation where the author felt she had not formed a relationship with the patient at all. In the second, the author questions whether the relationship had been over-involved and this is discussed in relation to the nature of involvement and what constitutes over-involvement. In the final practice episode the author felt that a positive relationship was formed with benefits to the patient concerned. The paper concludes by highlighting the importance of nurse-patient relationships in A&E, and how they can be formed in light of the barriers discussed previously.

Emergency Nursing↗

PubMed2004

Exploring options for improving healthcare.

New medical technologies generally must receive clearance or approval for marketing by the US Food and Drug Administration and be covered by an insurer, such as the Centers for Medicare and Medicaid Services, before becoming available for widespread clinical use. These 2 approval processes are discrete and usually occur sequentially rather than collaboratively and simultaneously. To explore potential mechanisms for increasing regulatory collaboration between these 2 key health care agencies, the Duke Clinical Research Institute and Health Strategies Consultancy convened an informal meeting of agency, academic, and industry leaders on December 8 and 9, 2002, titled "Registration/Approval and Coverage/Payment: Exploring Options for Improving Healthcare." This article arises from the discussion at this conference; it does not represent the official views of any person or institution involved. Although the group did not attempt to reach a consensus, it examined several important issues surrounding this regulatory debate. Herein are proposed options for enhancing regulatory efficiency through greater coordination between the FDA and CMS, and discussion of these proposals from the perspectives of members of both agencies, members of stakeholder organizations, and academic observers.

Biomedical Technology↗

PubMed2006

Exploring racial and ethnic disparities in prescription drug spending and use among Medicare beneficiaries.

BACKGROUND: Little is known about why minority Medicare beneficiaries spend less on and use fewer prescription drugs than white Medicare beneficiaries. OBJECTIVE: We explored whether population differences in demographic characteristics, socioeconomic status, and health status were associated with observed disparities by race and ethnicity in the prescription drug spending and use of noninstitutionalized elderly Medicare beneficiaries. METHODS: We used a nationally representative sample of 8101 white, 816 black, and 642 Hispanic Medicare beneficiaries from the 1999 Medicare Current Beneficiary Survey Cost and Use files. For each of these groups, we calculated total prescription drug spending, out-of-pocket spending, and number of prescriptions. We then used the Oaxaca-Blinder decomposition method to separate the impact of race and ethnicity on disparities in spending and use from the impact of differences in population characteristics across racial and ethnic groups. RESULTS: Much of the disparity in spending between whites and blacks and some of the disparity between whites and Hispanics can be attributed to race/ethnicity. Because of race/ethnicity, total spending for whites was 8.9% more than for blacks and 5.4% more than for Hispanics. Similarly, total out-of pocket spending for whites was 28.8% more than for blacks and 10.7% more than for Hispanics. Race/ethnicity also influenced the amount of prescription drug use. Whites used 2.3 more prescriptions than blacks and 1.6 more than Hispanics. However, these differences in use were offset by the impact of differences in population characteristics. CONCLUSIONS: Differences in factors identified in the Andersen model of access to care do not fully explain observed disparities in prescription drug use and spending. The portion of the disparities due to race and ethnicity may reflect patients' skepticism about medicine and medical care in general, patients' adherence to medical advice, patient-physician communication, physicians' prescribing habits, and usual source of care. Future research should explore whether these and other unobserved factors associated with race and ethnicity are responsible for disparities in drug spending and use.

Black or African American↗

PubMed2005

Distributed, intelligent, interactive visualization and exploration of time-oriented clinical data and their abstractions.

OBJECTIVES: We present KNAVE-II, an intelligent interface to a distributed architecture specific to the tasks of query, knowledge-based interpretation, summarization, visualization, interactive exploration of large numbers of distributed time-oriented clinical data, and dynamic sensitivity analysis of these data. KNAVE-II main contributions to the fields of temporal reasoning and intelligent user interfaces are: (1) the capability for interactive computation and visualization of domain specific temporal abstractions, supported by ALMA--a computational engine that applies the domain knowledge base to the clinical time-oriented database. (2) Semantic (ontology-based) navigation and exploration of the data, knowledge, and temporal abstractions, supported by the IDAN mediator, a distributed architecture that enables runtime access to domain-specific knowledge bases that are maintained by expert physicians. METHODS AND MATERIALS: KNAVE-II was designed according to 12 requirements that were defined through iterative cycles of design and user-centered evaluation. The complete architecture has been implemented and evaluated in a cross-over study design that compared the KNAVE-II module versus two existing methods: paper charts and an Excel electronic spreadsheet. A small group of clinicians answered the same queries, using the domain of oncology and a set of 1000 patients followed after bone-marrow transplantation. RESULTS: The results show that users are able to perform medium to hard difficulty level queries faster and more accurately by using KNAVE-II than paper charts and Excel. Moreover, KNAVE-II was ranked first in preference by all users, along all usability dimensions. CONCLUSIONS: Initial evaluation of KNAVE-II and its supporting knowledge based temporal-mediation architecture, by applying it to a large data base of patients monitored several years after bone marrow transplantation (BMT), has produced highly encouraging results.

Artificial Intelligence↗

PubMed2004

Deep space environments for human exploration.

Mission scenarios outside the Earth's protective magnetic shield are being studied. Included are high usage assets in the near-Earth environment for casual trips, for research, and for commercial/operational platforms, in which career exposures will be multi-mission determined over the astronaut's lifetime. The operational platforms will serve as launching points for deep space exploration missions, characterized by a single long-duration mission during the astronaut's career. The exploration beyond these operational platforms will include missions to planets, asteroids, and planetary satellites. The interplanetary environment is evaluated using convective diffusion theory. Local environments for each celestial body are modeled by using results from the most recent targeted spacecraft, and integrated into the design environments. Design scenarios are then evaluated for these missions. The underlying assumptions in arriving at the model environments and their impact on mission exposures within various shield materials will be discussed.

Aerospace Medicine↗

PubMed2004

The effects of heavy particle irradiation on exploration and response to environmental change.

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.

Aging↗

PubMed2005

Applied superconductivity and superfluidity for the exploration of the Moon and Mars.

We discuss how superconductivity and superfluidity can be applied to solve the challenges in the exploration of the Moon and Mars. High sensitivity instruments using phenomena of superconductivity and superfluidity can potentially make significant contributions to the fields of navigation, automation, habitation, and resource location. Using the quantum nature of superconductivity, lightweight and very sensitive diagnostic tools can be made to monitor the health of astronauts. Moreover, the Moon and Mars offer a unique environment for scientific exploration. We also discuss how powerful superconducting instruments may enable scientists to seek answers to several profound questions about nature. These answers will not only deepen our appreciation of the universe, they may also open the door to paradigm-shifting technologies.

Aerospace Medicine↗

PubMed2004

Infralimbic D1 receptor agonist effects on spontaneous novelty exploration and anxiety-like defensive responding in CD-1 mice.

Mesocortical dopamine (DA) terminals in the ventromedial prefrontal cortex (vmPFC) integrate cognitive/emotional processing functions underlying adaptive and appropriate behavioral responding to stressful environmental events. Results from several studies have also shown that stressor-enhanced prefrontal DA activation exerts detrimental effects on cognitive performance. However, questions have arisen as to whether stressor-enhanced vmPFC DA transmission exerts direct control over conditioned or unconditioned responses to threatening events, or whether enhanced prefrontal DA transmission gates cognitive processing to facilitate adaptive responding in threatening situations. We have previously shown that infralimbic (IL) vmPFC dopamine D2 agonist and antagonist drug infusions reduced anxiety-like responding in the elevated plus-maze (EPM) and disrupted spontaneous exploration in the Y-maze in CD-1 mice. In the present study, the effects of IL vmPFC infusions of the specific D1 receptor agonist, SKF-81297, in CD-1 mice were evaluated on spontaneous exploration in the Y-maze, anxiety-like responding in a 2-trial elevated plus-maze procedure, and anti-predator defensive responding in the Mouse Defense Test Battery (MDTB). SKF-81297 infusions disrupted spontaneous alternation performance along with potentiated repetitive 2-arm responding in the Y-maze. In the elevated plus-maze, pre-trial 1 IL SKF-81297 infusions reduced anxiety-like responding (enhanced open arm entries and time ratio, unprotected stretch attends and head dips), and reduced closed arm time ratio and protected risk assessment activity (protected stretch attends). In trial 2, 24h later (no drug infusions), open arm entries, open time ratio, and unprotected head dips remained enhanced relative to trial 2 vehicle controls. In the MDTB, avoidance distance was enhanced in the approach test; risk assessment (approach) was enhanced in the closed alley test; and defensive threat (upright postures) was enhanced in the forced contact test. Results are discussed with respect to possible influences of IL vmPFC DA receptors on cognitively mediated responding to differing levels of threat in mice.

Aggression↗

PubMed2004

'Looping'-an exploration mechanism in a dark open field.

The behavior of Tristram's jird (a species of gerbil) in an illuminated open field resembled that of other rodents, comprising round trips to a home base and alternating between periods of progression (locomoting) and of stopping. In this study, we compared the characteristics of exploration in a dark arena with exploration by the same individuals in a lit arena. In the dark arena, stopping episodes were brief and fewer, suggesting almost continuous locomotion by the rodents. The clear distinction between progression and stopping that had characterized locomotion in an illuminated arena, thus diminished in the dark. There was also no apparent home base in the dark and traveling consisted in moving in a circular path, closing a loop to a recently traveled place that varied from one loop to the next. Locomotion in the dark may thus be regarded as a set of loops (round trips) to a continuously shifting home base, whereas with lights on the round trips converge to a home base using visible environmental landmarks. We suggest that a similar looping mechanism may be applicable to the behavior of hippocampal rats displaying hyperactivity and diversified locomotion, reminiscent of that seen in jirds in a dark arena.

Animals↗

PubMed2026

Exploration of the antibacterial function of the Eutherian LEG1s.

Liver-enriched gene 1 (LEG1) encodes a novel protein family whose functions are not fully explored. LEG1 was first reported and characterized in zebrafish, where it encodes secreted proteins involved in liver development. In contrast, mammalian LEG1s exhibit a different expression pattern. The platypus monotreme lactation protein (platMLP) was uncovered in milk with antibacterial function. Studies in mouse and pig have shown that LEG1s are specifically expressed in the salivary glands; however, their function remains unclear. Evolutionarily, LEG1s are present in vertebrates and form three major clades, LEG1a, LEG1b, and LEG1c. Only a few invertebrates, protists, and bacteria retain LEG1 homologs, making the evolutionary origin of LEG1 obscure. In the current study, we conducted a thorough exploration of prokaryotic reference genomes and found that LEG1 predominantly exists in Actinomycetota. Given that Actinomycetota are well known for producing antibacterial compounds, and that platMLP can inhibit the growth of certain bacteria, we hypothesized that LEG1 is a conserved antibacterial protein. Recombinant LEG1s from each of the three clades were then purified and subjected to antibacterial tests, which showed that pig LEG1c and platMLP have divergent antibacterial activities. These findings support the hypothesis that the antibacterial function of LEG1 is conserved in eutherians but has undergone functional diversification following gene duplication events.

Animals↗

PubMed2004

Exploring QSAR of melatonin receptor ligand benzofuran derivatives using E-state index.

Considering the recent challenge to the medicinal chemists for the development of selective melatonin receptor ligands, an attempt has been made to explore physicochemical requirements of benzofuran derivatives for binding with human MT1 and MT2 receptor subtypes and also to explore selectivity requirements. In this study, E-states of different common atoms of the molecules (calculated according to Kier and Hall) and physicochemical parameters (partition coefficient and molar refractivity) were used as independent variables along with suitable dummy parameters. The best equation describing MT1 binding affinity [n = 34, Q2 = 0.670, Ra2 = 0.790, R2 = 0.822, R = 0.907, s = 0.609, F = 25.8 (df 5, 28)] suggests that the binding affinity decreases as the value of n (number of CH2 spacer beside R2) increases while it increases with rise in electrotopological state values of different atoms of the benzofuran ring. Again, presence of methoxy group at R1 and hydrogen, unsubstituted phenyl or fluoro-substituted phenyl group at R2 is conducive to the MT1 binding affinity. The binding affinity decreases if furyl substitution at R3 position is present. The best equation describing MT2 binding affinity [n = 34, Q2 = 0.602, Ra2 = 0.755, R2 = 0.792, R = 0.890, s = 0.584, F = 213 (df 5, 28)] shows that the MT2 binding affinity depends on the similar factors as described for MT1 binding affinity; however, the contributions of the factors for the two affinities are different to some extent as evidenced from the regression coefficients. Among the selectivity relations, the best equation [n = 33, Q2 = 0.496 Ra2 = 0.681, R2 = 0.721, R = 0.849, s = 0.458, F = 18.1(df 4, 28)] suggests that MT2 binding increases with increase in value of n, presence of methoxy group at R1, and E-state values of different atoms of the benzofuran ring, while it decreases in presence of furyl group at R3 position.

Benzofurans↗

PubMed2004

QSAR of adenosine receptor antagonists. Part 3: Exploring physicochemical requirements for selective binding of 1,2,4-triazolo[5,1-i]purine derivatives with human adenosine A3 receptor subtype.

Considering potential of selective adenosine A3 receptor antagonists in the development of prospective therapeutic agents, an attempt has been made to explore selectivity requirements of 1,2,4-triazolo[5,1-i]purine derivatives for binding with cloned human adenosine A3 receptor subtype. In this study, partition coefficient (logP) values of the molecules (calculated by Crippen's fragmentation method) and Wang-Ford charges of the common atoms of the triazolopurine nucleus (calculated from molecular electrostatic potential surface of energy minimized geometry using AM1 technique) were used as independent variables along with suitable dummy parameters. The best equation describing A3 binding affinity [n=29, Q2=0.796, Ra2=0.853, R2=0.874, R=0.935, s=0.342, F=41.5 (df 4,24), SDEP=0.396] showed parabolic relation with logP (optimum value being 4.134). Further, it was found that an aromatic substituent conjugated with the triazole nucleus should be present at R2 position for A3 binding affinity. Again, high negative charges on N2 and N4 are conducive to the binding affinity. While exploring selectivity requirements of the compounds for binding with A3 receptor over that with A2A receptor, the selectivity relation [n=23, Q2=0.909, Ra2=0.918, R2=0.933, R=0.966, s=0.401, F=62.4 (df 4,18), SDEP=0.412] showed that an aromatic R2 substituent conjugated with the triazole nucleus contributes significantly to the selectivity. Again, presence of a 4-substituted-phenyl ring (except 4-OH-phenyl and 4-CH3-phenyl) at R2 position also increases selectivity. Further, charge difference between N2 and N11 (negative charge on the former should be higher and that on the latter should be less) contributes significantly to the selectivity. In addition, negative charge on N7 is conducive while presence of substituents like propyl, butyl, pentyl or phenyl at R1 position is detrimental for the A3 selectivity.

Adenosine A3 Receptor Antagonists↗

PubMed2005

6-Acylamino-2-amino-4-methylquinolines as potent melanin-concentrating hormone 1 receptor antagonists: structure-activity exploration of eastern and western parts.

SAR explorations of the eastern and western parts of recently disclosed 2-aminoquinoline MCH1R-antagonists are reported. Eastern part investigations confirmed a high degree of structural freedom, and a number of additional single digit nanomolar antagonists were identified. Investigations of the western part also confirmed the initial SAR analysis, requiring a para-substituted phenyl ring spaced from the 6-amide by two connecting atoms. The exploration led to the discovery of a novel sub-series with a 4-biphenylcarboxamide western part, also exhibiting single digit nanomolar affinity.

Molecular Structure↗

PubMed2005

The Swedish epidemic of coeliac disease explored using an epidemiological approach--some lessons to be learnt.

Sweden has experienced an epidemic of symptomatic coeliac disease that has no likeness anywhere else in the world. This is quite unique for a disease that is genetically dependent, immune-mediated and chronic, and suggests an abrupt increase and decrease, respectively, of one or a few causal factors influencing a large proportion of Swedish infants during the period in question. We have shown that half of the epidemic was explained by an increase in the proportion of infants introduced to gluten in comparatively large amounts after breast-feeding had been ended. This was partly an effect of societal changes in national dietary recommendations and the food content of industrially produced infant foods. Thus, these changes over time in infant feeding practices had a large public health impact. In fact, when the Swedish epidemic began, the increase in incidence rate was larger in girls than in boys, as was the decrease during the post-epidemic period. Moreover, children born during summer had an increased risk for coeliac disease, possibly as they were mostly introduced to dietary gluten during winter when infections are more common. Notably, birth cohorts of the epidemic and post-epidemic periods differ considerably regarding coeliac disease occurrence at comparable ages, even when followed up to school age. A longer follow-up will reveal to what extent new cases develop later in life, and to what extent this difference in cumulative incidence remains. However, mass screening studies of both the epidemic and post-epidemic cohorts at comparable ages are also planned to determine to what extent 'silent' disease cases develop. Continuing to explore the Swedish epidemic of coeliac disease by means of an epidemiological approach provides a unique opportunity. This may include increasing our understanding of what determines the clinical expression of the disease, exploring the potentially causal role of environmental exposures, and possibly also identifying strategies for primary prevention.

Age Distribution↗

PubMed2006

Spirituality and clinical care: exploring developmental changes in nursing and medical students.

OBJECTIVE: This study identifies and assesses changes in spiritual experiences and the perceived importance of spiritual issues in nursing and medical students participating in a Spirituality and Clinical Care course. Students participated in the study by completing two survey instruments: the Spiritual Experience Index-Revised (SEI-R) and the Spiritual Importance (SI) scales. Differences from pretest to posttest by sex and by discipline (medicine vs nursing) and changes in spiritual maturity are assessed and analyzed. RESULTS: Data analyses explored discipline differences, sex differences, and changes in levels of spiritual maturity one year after the two-week course. Students (N = 416) participating in the course reflected a significant increase in perceived importance of spirituality in practice, with females of both disciplines showing greater increases than males, and students in nursing showing greater increases than students in medicine. Female students were more trusting than male students in spiritual measures for support. An interesting finding revealed that both male and female students evidenced reduced dogmatic perceptions over time, with medical students declining more sharply than nursing students. Finally, changes in the levels of spiritual maturity of the students were measured. Students in contrasting developmental groups (n = 127) regressed over time to more dogmatic and underdeveloped levels of spiritual maturity. CONCLUSIONS: Maintenance or advancement of spiritual development was the expected outcome as students began to develop the art of their practice. It was unexpected that students would regress to a more dogmatic or underdeveloped spiritual level. Several explanations for these findings are explored.

Adult↗

PubMed2003

Exploring General Practitioners' attitudes to homeopathy in Dumfries and Galloway.

This comparative quantitative study explored General Practitioners' (GPs) attitudes to homeopathy in Dumfries and Galloway, a predominantly rural area in South West Scotland where there is a local British Homeopathic Association Funded Homeopathic Clinic. It aimed to determine whether there was an association between expressed attitudes to homeopathy and a number of variables. Issues arising from the House of Lords Report on CAM were also explored. A self-administered questionnaire was addressed to all 135 GPs within Dumfries and Galloway. Descriptive statistics were used in the data analysis. The response rate was 75%. The NHS GP clinic accounted for 47% of total referrals for homeopathy. A total of 86.1% of GPs within Dumfries and Galloway were in favour of a local NHS Homeopathic Specialist Clinic. Forms of evidence most influential to GPs regarding homeopathy were: randomised controlled trials; audit data on patient outcomes; safety and patient satisfaction.

Attitude of Health Personnel↗

PubMed2004

An exploration of the support available to children who may wish to visit a critically adult in ITU.

There has been growing evidence to suggest that by not actively supporting children who have a critically ill loved one in an Intensive Therapy Unit (ITU), we may be doing them a great disservice. Decreased understanding and feelings of abandonment and helplessness can prevail. The primary purpose of this research was to explore the resources currently available to support a child with a critically ill adult member of their family (or significant other) in ITU, whom they may wish to visit. Available support for nursing staff that enables them to do this has also been explored. A descriptive postal survey was used in 2003 to collect data from 46 adult general and cardiothoracic ITUs nationally. The findings illustrated that there was a lack of written policy and very little written information for adult visitors regarding the needs of children who have a loved one in ITU. There was also a dearth of resources for nursing staff pertaining to children and their needs (when visiting a critically ill adult), including a lack of any formal or informal education on the subject. Clearly, restrictions were still being imposed on children visiting a loved one either by the well parent/carer or by the nursing staff, mainly for reasons unsubstantiated by research.

Adult↗