Supramolecular Architecture of the Coronavirus Particle.

Coronavirus particles serve three fundamentally important functions in infection. The virion provides the means to deliver the viral genome across the plasma membrane of a host cell. The virion is also a means of escape for newly synthesized genomes. Lastly, the virion is a durable vessel that protects the genome on its journey between cells. This review summarizes the available X-ray crystallography, NMR, and cryoelectron microscopy structural data for coronavirus structural proteins, and looks at the role of each of the major structural proteins in virus entry and assembly. The potential wider conservation of the nucleoprotein fold identified in the Arteriviridae and Coronaviridae families and a speculative model for the evolution of corona-like virus architecture are discussed.

Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.

Feasibility of commercial interferon-gamma-based methods for the diagnosis of latent Mycobacterium tuberculosis infection in Finland, a country of low incidence and high bacille Calmette-Guérin vaccination coverage.

The performances of the QuantiFERON-TB Gold in Tubes (QFGT), T SPOT-TB (ELISPOT) and the Mantoux test were compared for the diagnosis of latent tuberculosis infection in Finland, a country of low tuberculosis incidence. In Cohort A (16 students), freshly isolated peripheral blood mononuclear cells (PBMCs), and in Cohort B (21 school children), cryopreserved PBMCs, were used for the ELISPOT assay. Cryopreservation of cells in fetal calf serum, but not in serum-free medium, produced false-positive results. Discrepancies between the results of the assays were observed. It was concluded that the accuracy of these ex-vivo methods needs additional evaluation.

On nursing theories and evidence.

PURPOSE: To expand the understanding of what constitutes evidence for theory-guided, evidence-based nursing practice from a narrow focus on empirics to a more comprehensive focus on diverse patterns of knowing. ORGANIZING CONSTRUCT: Carper's four fundamental patterns of knowing in nursing--empirical, ethical, personal, and aesthetic--are required for nursing practice. A different mode of inquiry is required to develop knowledge about and evidence for each pattern. CONCLUSIONS: Theory, inquiry, and evidence are inextricably linked. Each pattern of knowing can be considered a type of theory, and the modes of inquiry appropriate to the generation and testing of each type of theory provide diverse sources of data for evidence-based nursing practice. Different kinds of nursing theories provide different lenses for critiquing and interpreting the different kinds of evidence essential for theory-guided, evidence-based holistic nursing practice.

A theory of dependent-care: a corollary theory to Orem's theory of self-care.

Dependent-care has its origins in people's requirements for regulatory care. The foundations for dependent-care are found in the ability of individuals to provide their required care. First introduced as a corollary to self-care, this work emerged through a process of reading and discussion. Models that support the theory of dependent-care are identified. Premises are stated. There is elaboration of the conceptualizations representing the work that has been done. There are still elements that need further development, such as specifying the enabling abilities of dependent-care agency and verifying and formalizing the various elements presented.

Leadership-scholarship integration: using the Neuman systems model for 21st-century professional nursing practice.

This article describes leadership and scholarship from the Neuman systems model as requisite for a true practice model necessary for 21st-century scientific professional nursing. A rationale for the integration of leadership and scholarship is provided along with markers to guide the leadership-scholarship protocol, which can be viewed as a scholarly research process. An example from a community nursing center demonstrating the application of the integration of leadership-scholarship is presented to support the proposed integration.

The Neuman systems model in research and practice.

The major focus of this article is on utilization of the Neuman systems model for nursing practice and research. The directives given will accommodate cultural variations and also serve the needs of interdisciplinary groups. The author shares views of global values for using the Neuman systems model for relevant nursing education, practice, administration, research, and international and interdisciplinary functions.

[Fatalities in drug-dependent patients. A critical analysis]. / Todesfälle von Drogensüchtigen. Eine kritische Analyse.

The disquieting increase in the mortality of drug addicts observed in recent years cannot be ascribed to only one or a few well defined causes, such as the spread of the HI virus or AIDS, changes in drug consumption habits of multiple dependents or ineffective therapeutic measures. Primarily, an interaction of medical, social and psychological causes is emerging. In a well-defined addict population, 35 deaths of intravenous drug users were registered in the period 1987-1990. By comparison, 7 deaths were recorded in the same geographical area between 1983 and 1986. A report of the UN Commission on Narcotic Drugs shows that in Western Europe, mortality in this high-risk group has doubled annually in the past few years.

Air transport.

Air transport has become an integral element of pediatric transport programs. The use of both fixed-wing (airplane) and rotorwing (helicopter) aircraft has increased. Appropriate vehicles configured for the safe and effective transfer of pediatric and neonatal patients are available. As the acuity of patients requiring air transport has increased, more sophisticated and specialized training in the areas of flight physiology and transport medicine is required. The limitations of air transport and air transport vehicles must be understood to assure that the optimal modality is selected for a specific transport.

Transport of the critically ill patient with upper airway obstruction.

Upper airway obstruction is a life-threatening emergency requiring prompt evaluation and careful intervention. The pathophysiology of upper airway obstruction is reviewed. Assessment techniques and stabilization are discussed with specific attention to intervention and stabilization prior to transport.

Nursing actions to prevent and alleviate pain in hospitalized children.

Nurses are confronted daily with the responsibility to care for hospitalized children in pain, yet the substantive knowledge base about that care and how effective it is remains extremely limited. Although there is initial evidence of effectiveness of several pharmacologic and nonpharmacologic pain relief approaches, little evidence of use or effectiveness in clinical nursing practice exists. To begin to address this knowledge deficit, two studies conceptualized within Orem's (1991) general theory of nursing were undertaken: one involving ethnographic interviews to determine what pain relief actions are taken by nurses with recognized expertise in caring for children in pain and another, follow-up survey to examine the frequency with which these actions are used by general nursing staff. Data about perceived effectiveness of the actions were also obtained. The results of these two studies of nursing actions to prevent and alleviate pain in hospitalized children document that nurses use a wide variety of creative methods to relieve pain. From interviews with the nurse experts both specific actions and action patterns and themes were identified. Furthermore, these patterns were congruent with methods of helping used by nurses as described by Orem. Results of this research currently serve as the basis for development and testing of nursing action protocols for alleviation of pain in hospitalized children.

Health as a continuum based on the Neuman systems model.

The following presentation, "Health as a Continuum," is based on the Neuman systems model. New relationships are made with the created-environment and energy as concepts in viewing and defining health on a continuum. Two case studies illustrate these views. An in-depth consideration of environment has important implications for wholistic nursing care and research.

Teen sexuality in a rural community.

A survey of adolescents and adults was conducted to assess the causes of the teen pregnancy problem in one rural community. Thirty teens and 34 adults were interviewed and asked to respond to questions related to teen sexuality/pregnancy. The goal of the analysis was to determine differences between and similarities among adults' and teens' perceptions of teen sexuality. Results showed few significant differences between the two groups. Nonsignificance, therefore, was significant.

Biochemical and functional properties of large and small dense-core vesicles in sympathetic nerves of rat and ox vas deferens.

A comparative study of the noradrenaline storing vesicles in vas deferens from ox and rat was performed. Microsomal fractions were subjected to density gradient centrifugation. In rat, noradrenaline and dopamine beta-hydroxylase were mainly present in the upper fractions of the gradient, which is consistent with the predominance of light (small dense-core) vesicles in this species. In ox, noradrenaline, dopamine and dopamine beta-hydroxylase were found in the gradient in a bimodal distribution. This is consistent with the presence of about equal numbers of small and large dense-core vesicles in this species. On the other hand, chromogranin A, immunologically related proteins and enkephalin-like immunoreactivity were only present in the dense (large dense-core) vesicle population. In order to study the capability of light and dense vesicles to synthesize noradrenaline we "pulse-labelled" ox vasa deferentia with [3H]tyrosine. Already 3.5 min after the pulse both types of vesicles contained [3H]noradrenaline and [3H]dopamine. During longer "chase" periods the amount of [3H]dopamine gradually declined. We conclude that dense (large dense-core) vesicles contain chromogranin A, immunologically related proteins and enkephalin-like immunoreactivity whereas light (small dense-core) vesicles are devoid of these components. Both types of vesicles contain dopamine beta-hydroxylase and can synthesize noradrenaline from dopamine under in vivo conditions.

Managing rate adjustments by health care providers.

Health care managers must be prepared to assess the impact of changes in the environment that differ from the planning scenario used in developing the budget. Even though rate adjustments cannot now be made at frequent intervals for a variety of reasons like administrative actions, board policies and legal prohibitions, the effective administrator will be aware of the impact of infrequent adjustments. What we imply in this paper is that administrators must be able to assess the impact of cost and volume changes on the rate structure more frequently than once a year if timely decisions on rate adjustments are to be made. The model developed here offers a tool to aid decision makers in this task.