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Research from afar: considerations for conducting an off-site research project.

An off-site research project is defined as a research study having a conduction location and data-collection site from which the principal investigator is geographically separated. Off-site research projects will likely increase because they afford greater access to larger research subject pools relevant to research questions and allow participation research at a site from which research would otherwise not be conducted. The critical elements proposed to make an off-site study successful include system negotiations, attending to personnel issues, fostering communication, encouraging subject participation, optimizing data collection and management, considering privacy issues, and ensuring optimal research team performance. An example of a specific off-site study involving a major midwest research university in one state and a large United States Navy training center in another state is discussed, and essential elements in establishing off-site research are highlighted.

Communication↗

Reflections on clinician leadership and management in mental health.

OBJECTIVE: To review the role of clinician leadership in the management of mental health services. CONCLUSIONS: The literature suggests that clinician leadership is increasingly regarded as an essential element in the effective introduction of innovation and improved quality of clinical care by those who manage mental health services. Psychiatrist leaders have a role to play in ensuring that service change and innovation is based on sound clinical values, is developed in partnership with clinicians and is understood and supported by psychiatrist colleagues. Clinician leaders require clear vision, commitment and courage. The support of their colleagues is essential if the psychiatric profession is to have influence on future development of mental health services.

Australia↗

Education needs for integrated care: a literature review.

AIM: This paper reports a systematic review to identify the education needs of the workforce within primary care to promote the effective delivery of integrated health and social care services. BACKGROUND: The need for different professionals to work more closely dominates global health policy. The drive to develop a workforce prepared for the future is crucial to the success of integrated services. However, some have argued that nurses are ill-equipped to meet the challenges of integrated service provision. The ability to work interprofessionally is an important skill which needs to be developed to support integrated working. METHODS: Structured searches were undertaken on organizational websites and the Caredata, CINAHL, Cochrane Library, MEDLINE, Sociofile databases between December 2002 and April 2004 to identify policy documents and primary research studies. The robustness of identified research studies were appraised using recognized appraisal tools. FINDINGS: Six themes were identified which indicate essential elements needed for integrated care. The need for effective communication between professional groups within teams and an emphasis on role awareness are central to the success of integrated services. In addition, education about the importance of partnership working and the need for professionals to develop skills in relation to practice development and leadership through professional and personal development is needed to support integrated working. CONCLUSION: Education which embeds essential attributes to integrated working is needed to advance nursing practice for interprofessional working. Further research exploring this and its impact on integrated provision is essential to ensure that evidence-based services are provided. The reinforcement of partnerships between higher education institutions and health and social care organizations should ensure that the workforce is educated to manage continuous change in service delivery. Innovative ways of teaching and learning which promote inter-professional working need to be explored.

Attitude of Health Personnel↗

Cell type-specific expression of the mouse peripherin gene requires both upstream and intragenic sequences in transgenic mouse embryos.

Peripherin is a neuron-specific type III intermediate filament protein expressed in well-defined populations of neurons projecting towards peripheral targets. To investigate the molecular mechanisms by which a gene is expressed in a specific subset of neurons, we used a transgenic approach in order to define peripherin gene sequences that are necessary for cell-type specific expression. Transgenic mice carrying different various genomic regions of the mouse peripherin gene fused to the Escherichia coli lacZ reporter gene were generated. We used three different peripherin/lacZ constructs containing either 5.8 kb upstream sequences, or both 5.8 kb upstream and 1.1 kb intragenic sequences, or 1.1 kb intragenic sequences associated with an heterologous promoter. Analysis of lacZ gene expression in transgenic mouse embryos showed that cell type-specific expression of the mouse peripherin gene requires both upstream and intragenic sequences. Analysis of transgenic mouse lines expressing the construct containing both upstream and intragenic sequences showed that this transgene contains all regulatory elements essential for both spatial and temporal expression of the mouse peripherin gene during embryogenesis. Furthermore, lacZ+ positive cells isolated from these transgenic lines by fluorescence-activated cell sorting (FACS) can be stained with a peripherin antibody, demonstrating that the transgene containing both upstream and intragenic sequences is expressed in peripherin neurons. These mouse peripherin upstream and intragenic sequences can now be used to identify cis-acting regulatory elements and transcription factors involved in peripherin gene regulation.

Animals↗

Selenium speciation analysis using inductively coupled plasma-mass spectrometry.

Selenium exists in several oxidation states and a variety of inorganic and organic compounds, and the chemistry of selenium is complex in both the environment and living systems. Selenium is an essential element at trace levels and toxic at greater levels. Interest in speciation analysis for selenium has grown rapidly in this last decade, especially in the use of chromatographic separation coupled with inductively coupled plasma-mass spectrometry (ICP-MS). Complete characterization of selenium compounds is necessary to understand selenium's significance in metabolic processes, clinical chemistry, biology, toxicology, nutrition and the environment. This review describes some of the essential background of selenium, and more importantly, some of the currently used separation methodologies, both chromatographic and electrophoretic, with emphasis on applications of selenium speciation analysis using ICP-MS detection.

Chromatography, Gas↗

Transcriptional regulation in endoderm development: characterization of an enhancer controlling Hnf3g expression by transgenesis and targeted mutagenesis.

The hepatic nuclear factor 3gamma (Hnf3g) is a member of the winged helix gene family of transcription factors and is thought to be involved in anterior-posterior regionalization of the primitive gut. In this study, cis-regulatory elements essential for the expression of Hnf3g in vivo have been characterized. To this end, a 170 kb yeast artificial chromosome (YAC) carrying the entire Hnf3g locus was isolated and modified with a lacZ reporter gene. The two mouse lines carrying the unfragmented Hnf3g-lacZ YAC showed tissue-specific, copy number-dependent and position-independent expression, proving that 170 kb of the Hnf3g locus contain all elements important in the regulation of Hnf3g. Cis-regulatory elements necessary for expression of Hnf3g were identified in a three-step procedure. First, DNase I hypersensitive site mapping was used to delineate important chromatin regions around the gene required for tissue-specific activation of Hnf3g. Second, plasmid-derived transgenes and gene targeting of the endogenous Hnf3g gene locus were used to demonstrate that the 3'-flanking region of the gene is necessary and sufficient to direct reporter gene expression in liver, pancreas, stomach and small intestine. Third, a binding site for HNF-1alpha and beta, factors expressed in organs derived from the endoderm such as liver, gut and pancreas, was identified in this 3'-enhancer and shown to be crucial for enhancer function in vitro. Based on its expression pattern we inferred that HNF-1beta is a likely candidate for directly activating Hnf3g gene expression during development.

Animals↗

Alterations of bone marrow sinus endothelium induced by ionizing irradiation: implications in the homing of intravenously transplanted marrow cells.

The endothelium of bone marrow sinuses is a continuous layer which is selective in its cellular transport. It is not known how selective and massive seeding of hemopoietic progenitor cells after intravenous transplantation of marrow cells occurs. We postulate that the conditioning irradiation could disrupt the endothelial barrier, thus permitting the "homing" of progenitor cells to occur. To demonstrate this phenomenon, we irradiated mice with doses ranging from 100-2000 cGy-total body and studied perfusion-fixed marrow by transmission electron microscopy. The major finding was sloughing and denudation of plasma membrane, particularly on the luminal side of endothelium. Membrane vesiculation was also frequently seen in this border. Moreover, dilatation of the perinuclear space and rough endoplasmic reticulum was commonplace and testified to instability and fragility of the membrane system. Focal cytoplasmic swelling of endothelium was seen reflecting increased permissiveness of the endothelial barrier. Endocytosis and phagocytosis were increased in the marrow; and the endothelium, normally quiescent with regard to phagocytosis, was now overtly phagocytic. A dipogenecity of the adventitial layer was increased as hemopoietic function of marrow decreased. The end result of membrane alterations in the endothelium was the appearance of discontinuities in these cells, which form the essential element of bone marrow-blood barrier. Consequent to these discontinuities, the permissiveness of the endothelial barrier was enhanced and those cellular elements, such as mature, nonreticulated erythrocytes that are normally confined to the vascular space, now appeared in large number in the hemopoietic compartment. With low doses, these findings were transient and repair set in by 1-2 weeks. With higher doses, total disruption of marrow-blood barrier occurred and the process did not seem to be repairable. We conclude that the conditioning irradiation before bone marrow transplantation is essential in disrupting the endothelial barrier and permitting large-scale entry of transplanted cells into the hemopoietic compartment.

Animals↗

Elevated concentrations of trace elements in Caspian seals (Phoca caspica) found stranded during the mass mortality events in 2000.

Concentrations of V, Mn, Fe, Cr, Co, Cu, Zn, As, Se, Mo, Ag, Cd, Tl, Hg, Pb, and organic mercury (Org-Hg) were determined in liver, kidney, and muscle of healthy Caspian seals ( Phoca caspica) collected in 1998. These concentrations were compared with those of seals infected with canine distemper virus (CDV) found stranded along the coastal areas in 2000. Concentrations of toxic elements (As, Ag, Cd, Tl, Hg, Pb, and Org-Hg) in Caspian seals stranded in 2000 were comparable or lower than those of samples collected in 1998 and in other pinnipeds. Thus it may be inferred that these elements were not the causative agents in the deaths of the seals. In contrast, concentrations of Zn and Fe were much higher in diseased Caspian seals than those in other pinnipeds. Zinc concentrations in all tissues of Caspian seals also increased during 1993-2000. Furthermore, negative correlations were found between blubber thickness and hepatic and renal Zn concentrations. These results imply the disturbance in homeostatic control and nutritional status of essential elements in Caspian seals stranded in 2000.

Animals↗

Enriched stable isotopes of elements used as tracers: methods of presenting high-performance liquid chromatographic-inductively coupled argon plasma mass spectrometric data.

High-performance liquid chromatography (HPLC) of biological fluids and tissue cytosolic preparations was employed in conjunction with argon-induced inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of stable isotopes as tracers. The common way of presenting the data from the ICP-MS is by plotting the count rates versus the retention time of HPLC fractions. Additional information can be derived, e.g., the composite peaks can be further resolved, and the level of enrichment in various biological components can be expressed by alternative ways of presenting these data. The two additional approaches described here involve presenting the ratios of enriched tracer with a suitable naturally abundant mass number of the same element, and by expressing the extent of enrichment by the tracer isotope in a given fraction to that of the same mass number in the fraction derived from an untreated source. Each method of presentation has different merits and drawbacks. The data therefore may be best presented in more than one way to emphasize the conclusions from a given experiment. Observations are presented after simultaneously injecting stable isotopes of three essential elements, copper, selenium and zinc, into mice. Plasma and liver cytosolic fractions were analysed and data represented in different ways as indicated above.

Animals↗

Cadmium--influence on biochemical processes of the human organism.

Heavy metals are too well-known environmental pollutants of particularly dangerous effect to human health. Because of their wide usage in many industrial branches they are present everywhere in the air, water and soils. Food contamination by heavy elements is hard to avoid and it is a result of environmental contamination by dusts, industrial gases, sewage, waste and coal burning processes. One of the most harmful heavy metals, widely spread in nature is cadmium. Toxic cadmium action involves free oxygen generation and inactivation of protein containing cysteine residues with -SH groups. It influences many metabolic processes causing great damage in many organs. Cadmium can also interact with some essential elements leading to their homeostasis disorders.

Cadmium↗

[Appropriate technologies in food: conceptual framework for their generation and transfer in Central America and Panama].

A conceptual framework is presented, expressing the relationship between food availability and the food and nutritional status of a population. As element of the model, the generation and transfer of appropriate food technologies were included. Based on the conceptual framework, three successful cases of food technology transfer in the Central American area were analyzed. The most important aspects of each case were identified, and a critical review of the characteristics and conditions required to generate and transfer appropriate technologies, was carried out. An inventory was made of those factors which are essential for a food technology to be appropriate; this analysis resulted in the postulation of a model describing the life cycle of appropriate food technologies. On these bases, several guidelines are postulated, which could constitute a conceptual framework to help guide actions in the generation and transference of appropriate food technologies in Central America and Panama. Essential elements of the proposed framework are: identification and characterization of the problem of the group of "users" of the technology; problem solution by a multidisciplinary group; test of the technology and evaluation of its feasibility (technical, economical, political, social and cultural), and controlled transference to the group of "users".

Central America↗

Gene expression and gene therapy imaging.

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters.

Animals↗

Erythropoietin, iron metabolism, and red blood cell production.

Erythropoietin (EPO) plays a central role in the regulation of red blood cell (RBC) production. Since iron is an essential element for erythropoiesis and hemoglobin (Hb) synthesis, its importance is heightened in patients treated with epoetin alfa. Stimulation of erythropoiesis following the administration of epoetin alfa is associated with several changes in iron metabolism; indeed, plasma ferritin levels fall as a result of increased utilization of iron by the expanding erythroid marrow. The administration of epoetin alfa can therefore lead to a state of relative iron deficiency. Thus, iron supplementation is essential to maximize the effect of epoetin alfa-induced erythropoiesis.

Adult↗

Planning for the future: advanced nursing practice in critical care.

The subject of advanced nursing practice has become a topic of great interest and considerable debate in recent years. It has as a concept, however, been increasingly obscured by the plethora of terms used to denote its particular role and function. The purpose of this paper is to suggest how a consensus may be achieved in terms of role clarification, educational preparation, intellectual skill, level of performance and remuneration. Fundamental elements of the current debate are seen to be the need for advanced nursing practice, how it will be recognized in practice, the parameters of the expanding role and the centrality of the patient rather than professional boundaries in delineating advanced nursing practice for critical care. The debate will no doubt continue. It is not the aim of this paper to reach a definitive understanding, but to provide a platform so that essential elements can be confronted and the development of the role carefully considered.

Clinical Competence↗

Supportive and inhibitory elements of a putative PrfA-dependent promoter in Listeria monocytogenes.

Elements essential for PrfA-dependent transcription were analysed on two promoters of Listeria monocytogenes, the PrfA-dependent promoter of the phospholipase gene plcA (PplcA) and a putative promoter of the aroA gene (ParoA2) which contains a similar PrfA-binding site and a similar -10 box as PplcA but does not function as PrfA-dependent promoter. We constructed a series of hybrid plcA-aroA promoters by exchanging corresponding sequence elements of these two 'promoters'. The results showed that the two critical elements of PrfA-dependent promoters, the PrfA-box and the -10 box, can be functionally exchanged as long as the distance in between is maintained to 22 or 23 bp. However, the interspace sequence and the sequence downstream of the -10 box of ParoA2 were strongly inhibitory for PrfA-dependent transcription. A detailed analysis of these two sequences revealed that the RNA polymerase binding site being part of the actual in vivo and in vitro used aroA promoter (ParoA1) and a sequence immediately downstream of the putative -10 site, possibly blocking the formation of the open complex, were responsible for the inhibition of PrfA-dependent transcription from ParoA2. Taking into consideration the lessons learned from this study we were able to construct a functional PrfA-dependent aroA promoter.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

Gang violence.

During childhood and adolescence, the formation of groups or gangs is a normal part of the growing process. Playmates, school friends, Boy and Girl Scout troops are each examples of the natural inclination to form group attachments that provide a stable social outlet. However, gangs, as we now know them, are part of the pathological process brought on by the inability to disassociate from adolescent groupings, and more frightening, the result of infiltration by criminal elements, such as drug dealers, who exert violent influence on impressionable youngsters, particularly in major urban areas. The transition of gangs from innocent to deadly is due in large part to society's failure to respond to the environment that causes their pathology. In order to reverse the process, society must engage in programs that reinforce the gang or group experience as a positive one by incorporating adult supervision and mentoring as essential elements.

Adolescent↗

Role of zinc in regulating the levels of hepatic elements following nickel toxicity in rats.

This study was designed to determine the protective effects of zinc on the hepatotoxicity induced by nickel in rats. Female Sprague-Dawley (SD) rats received either nickel sulfate alone in the dose of 800 mg/L nickel in drinking water, zinc sulfate alone in the dose of 227 mg/L zinc in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. The effects of different treatments were studied on activities of rat liver marker enzymes like alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferases (AST) and on the status of essential elements in rat liver. The study revealed a significant increase in the activities of enzymes ALP and ALT in rats subjected to nickel treatment. Interestingly, zinc supplementation to rats treated with nickel brought back the raised activities of these enzymes to within normal limits. Further, the levels of elements in liver that include zinc, copper, selenium, and potassium were found to be significantly suppressed following nickel treatment, whereas the levels of iron and sulfur were elevated. However, zinc treatment alone did not cause any appreciable change in the concentration of these elements. To the contrary, when zinc was given to nickel-treated rats, the concentrations of zinc, copper, potassium, and phosphorus were not significantly different from that of normal controls, whereas the levels of iron, selenium, and sulfur were improved in comparison to nickel-treated rats but were not within the normal limits. The present study concludes that zinc has the ability to maintain the levels of hepatic elements and has bearing in regulating the liver functions by maintaining the activities of marker enzymes in conditions of nickel toxicity.

Alanine Transaminase↗

Sloppier copier DNA polymerases involved in genome repair.

When chromosomal replication is impeded in the presence of DNA damage, members of a newly discovered UmuC/DinB/Rev1/Rad30 superfamily of procaryotic and eucaryotic DNA polymerases catalyze translesion synthesis at blocked replication forks. Although these polymerases share sequence elements essentially unrelated to the standard replication and repair enzymes, some of them (such as the SOS-induced Escherichia coli pol V) catalyze 'error-prone' translesion synthesis leading to large increases in mutation, whereas others (an example being the Xeroderma pigmentosum variant gene product XPV pol eta) carry out aberrant, yet nonmutagenic translesion synthesis. Ongoing studies of these low fidelity polymerases could provide new insights into the mechanism of somatic hypermutation, a key element in the immune response.

Animals↗