Open field activity and EtOH activation of gamma-PKC null mutants.

Null mutants of the neural-specific gamma-isotype of protein kinase C (gamma-PKC) have demonstrated differential responses to acute administration of ethanol in comparison with wild-type animals. Previous studies have shown that the mutants are less sensitive to ethanol-induced loss of righting response. Null mutants also consume more ethanol and exhibit less behavioral inhibition. In order to determine if these sensitivity differences extend to ethanol activation of locomotor activity in an open-field arena, baseline activity and the effect of two low doses of ethanol were assessed in gamma-PKC null mutants and wild-type littermates. Null mutants demonstrated higher levels of baseline activity than did their wild-type counterparts. Further analysis revealed that a 1.0 g/kg dose of ethanol increased locomotor activity in males and females of both genotypes, whereas only null mutant males were activated by a 1.25 g/kg ethanol dose. The current study demonstrates that male gamma-PKC null mutants exhibit increased sensitivity to activating doses of ethanol in contrast to previous findings of decreased sensitivity to higher, depressive doses. This reflects the pleiotropic effects of the gamma-PKC null mutation on the behavioral effects of ethanol.

Working toward consensus: providers' strategies to shift patients from curative to palliative treatment choices.

End-of-life decision making is a complex phenomenon and providers, patients, and families often have different views about the appropriateness of treatment choices. The results presented here are part of a larger grounded-theory study of reconciling decisions near the end of life. In particular, we examined how providers (N = 15) worked near the end of patients' lives toward changing the treatment decisions of patients and families from those decisions that providers described as unrealistic (i.e., curative) to those that providers described as more realistic (i.e., palliative). According to providers, shifting patients' and families' choices from curative to palliative was usually accomplished by changing patients' and families' understanding of the patient's overall "big picture" to one that was consistent with the providers' understanding. Until patients and families shifted their understanding of the patient's condition-the big picture-they continued to make what providers judged as unrealistic treatment choices based on an inaccurate understanding of what was really going on. These unrealistic choices often precluded possibilities for a "good death." According to providers, the purpose of attempting to shift the patient or proxy's goals was that realistic goals lead to realistic palliative treatment choices that providers associated with a good death. In this article we review strategies used by providers when they believed a patient's death was imminent to attempt to shift patients' and families' understandings of the big picture, thus ultimately shifting their treatment decisions.

Ethanol consumption and behavioral impulsivity are increased in protein kinase Cgamma null mutant mice.

Etiological factors influencing the development of alcoholism are complex and, at a minimum, include an interaction between polygenic factors and personality and biological traits. Human and animal studies suggest that some genes may regulate both the traits associated with alcohol abuse, such as decreased sensitivity or anxiety, and vulnerability to alcoholism. The identification of these genes could elucidate neurochemical pathways that are important in the development of alcohol abuse. Results from the present study indicate that the gene encoding the neuronal-specific gamma subtype of protein kinase C (PKCgamma) influences both ethanol consumption and behavioral impulsivity, a personality characteristic associated with Type II alcoholics, in a pleiotropic manner. Mice lacking PKCgamma consume more ethanol in a two-bottle choice paradigm and also demonstrate increased behavioral impulsivity in an appetitive-signaled nosepoke task when compared with wild-type littermate control mice. Therefore, PKCgamma may be an important mechanism within the cell that mediates one or more neurochemical pathways relevant to an increased predisposition to alcoholism.

Expanding conceptualizations of culturally competent care.

AIM: The aim of the study was to gain an understanding of cultural competence from the perspectives of non-mainstream nurse educators, specifically those of Latin heritage. BACKGROUND/RATIONALE: Although the theoretical concepts of 'cultural diversity' and 'culturally competent care' have been supported and promoted by the largest professional nursing organizations, the practical application of these concepts has often created difficulties for nurse researchers, educators, and clinicians. The lack of progress in teaching and evaluating cultural competence suggested the need to 'center the margins' and explore cultural competence from the margins of one particular non-mainstream nursing group, Latina nurse educators. DESIGN/METHODS: A grounded theory research design was employed. A group of 10 doctoral, prepared, self-identified, Latina nurse educators participated in face- to-face audiotaped interviews. Data collection, analysis, and theoretical sampling decisions occurred concurrently, strengthening theory generation. Institutional review board approval was received for all steps of the study. The major limitation of the study was the omission of student voices. RESULTS/FINDINGS: The analysis suggests that the Latina participants shared the common purpose of teaching students how to think about difference. The teaching practices of this group of Latina educators was based on a belief that 'difference' is not solely about specific cultural groups. For example, content about 'Hmongs' or 'Latinos'. Rather, Latina faculty focused on teaching students how to directly connect with anyone perceived as different from oneself. CONCLUSION: Latina faculty did not distinguish between competent care and culturally competent care; for them, competence necessarily includes cultural competence. They conceptualize the provision of competent care to all persons who are perceived as different, rather than focusing only on those who are perceived as 'culturally' different. These conceptualizations have the potential to shed new light on how nurses and nurse educators think about, develop, and integrate cultural competence into nursing education, practice, and research.

Care-as-service, care-as-relating, care-as-comfort: understanding nursing home residents' definitions of quality.

PURPOSE: This study explored how nursing home residents define quality of care. DESIGN AND METHODS: Data were collected through in-depth interviews and were analyzed using grounded dimensional analysis. RESULTS: Residents defined quality in three ways: (a) Care-as-service residents focused on instrumental aspects of care. They assessed quality using the parameters of efficiency, competence, and value. (b) Care-as-relating residents emphasized the affective aspects of care, defining quality as care that demonstrated friendship and allowed them to show reciprocity with their caregivers. (c) Care-as-comfort residents defined quality as care that allowed them to maintain their physical comfort, a state that required minute and often repetitive adjustments in response to their bodily cues. IMPLICATIONS: Residents' perceptions of care quality have implications for long-term care practice. The integration of these perceptions into quality assurance instruments could improve the usefulness of tools designed to obtain resident input.

Quantitative genetics and mouse behavior.

Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.

Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKCgamma null mutant mice.

Tests of ethanol effects in PKCgamma null mutant mice have indicated that PKCgamma plays a role in initial sensitivity to ethanol-induced sedation, hypothermia, and GABA(A) receptor function and impacts neurochemical pathways mediating anxiety. The present study was undertaken to evaluate whether the decreased sensitivity to ethanol previously observed in these mice generalized to the anxiolytic effects of ethanol. PKCgamma null mutant mice and wild-type controls were tested in the elevated-plus maze, the black/white box, and the mirrored chamber after ethanol (0, 1.0, 1.25, 1.5 g/kg) or flunitrazepam (FNZ) (0, 0.015, 0.03, 0.06 mg/kg). Results indicated that although both genotypes exhibited anxiolytic responses to ethanol in the elevated plus-maze, null mutant mice were less sensitive than wild-type control mice; however, in the black/white box, PKCgamma null mutants were more sensitive than controls to the anxiolytic effects of FNZ. Neither ethanol nor FNZ produced anxiolytic responses in the mirrored chamber for either genotype. These results suggest that PKCgamma differentially mediates anxiolytic responses to ethanol and FNZ and that this relationship interacts with each drug's efficacy in reducing anxiety-related behaviors specific to each of the three mazes.

How nurses manage time and work in long-term care.

AIMS OF THE STUDY: The aim of this study was to better understand the ways in which conditions of work, including staffing, affect how nurses in long-term care (LTC) facilities do their jobs and the quality of care they provide. BACKGROUND: The research reported here was performed in the context of public policy debates about the relationship between staffing levels and quality in LTC. METHODS: In 1995 and 1996, interviews and participant observation were used to examine how 18 licensed nurses employed in two LTC facilities in the midwestern United States experience their day-to-day work. RESULTS: Time was an extremely salient work condition for the nurses interviewed. Under conditions of too little time and many interruptions, nurses compensated by developing strategies to keep up or catch up. These strategies included minimizing the time spent doing required tasks, creating new time and redefining work responsibilities. Although these strategies allowed nurses to complete the tasks for which they were accountable, there were adverse consequences for nurses and residents. Nurses realized that time demands often made it impossible to provide care of high quality. They expressed their ideas about quality care as the notion of 'should do' work. In effect, time pressures forced them to forego the 'should do' work to complete the 'must do' work. CONCLUSION: Increased staffing could improve the quality of care in LTC facilities.

Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.

Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.

GABA(A)-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol.

BACKGROUND: The gamma-aminobutyric acid type A receptors (GABARs) are involved in mediating some of the behavioral effects of beverage alcohol (ethanol). However, the unique pharmacological and behavioral responses conferred by each of the various receptor subunits are not well understood. METHODS: To address the role of the GABAR delta subunit in mediating ethanol responses, gene knockout mice that lack this subunit were tested for a variety of ethanol-induced behavioral responses. RESULTS: Our results indicate that, compared with controls, delta-deficient mice (delta-/-) have (1) reduced ethanol consumption, (2) attenuated withdrawal from chronic ethanol exposure, and (3) reduced anticonvulsant (seizure-protective) effects of ethanol. These mice demonstrate a normal anxiolytic response to ethanol and a normal hypothermic response to ethanol, and they develop both chronic and acute tolerance. CONCLUSIONS: These results further establish the link between GABARs and specific behavioral responses to ethanol and begin to reveal the role of the delta subunit in these responses.

Serotonin 5-HT(2) receptor stimulation of dopamine release in the posterior but not anterior nucleus accumbens of the rat.

The objective of the present study was to examine the involvement of serotonin 5-HT(2) receptors within the rat nucleus accumbens (Acc) in the regulation of dopamine (DA) release using in vivo microdialysis. Perfusion with the 5-HT(2) agonist (+)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), at concentrations of 25-250 microM, through microdialysis probes located in the posterior Acc increased extracellular DA levels to a maximum of 200% of baseline. DOI-induced increases in the extracellular levels of DA were Ca(2+) dependent and were inhibited by co-perfusion with the 5-HT(2) antagonist LY-53,857. DOI enhancement of the extracellular concentrations of DA was observed when probes were implanted in the Acc core and shell regions posterior to anteroposterior +1.2 mm from bregma, whereas a small reduction in the extracellular levels of DA was observed in the anterior Acc. There were no differences between core and shell subdivisions within either the anterior or the posterior Acc. These results suggest that activation of 5-HT(2) receptors within the posterior, but not anterior, Acc stimulates DA release, indicating rostral-caudal differences in the interactions of 5-HT with DA systems in the Acc.

Patient-centered care: understanding its interpretation and implementation in health care.

Providing patient-centered care (PCC) has been the focus of recent organizational restructuring and quality improvement efforts in health care. Much has been written about PCC in the past 5 years; however, there are multiple perspectives about the interpretation and implementation of this concept. Descriptions of PCC in the health care literature generally, in some way, refer to meeting patients' needs. Literature describing PCC falls into two categories. The first category interprets PCC as the reorganization of services around patients' needs. The second defines PCC as understanding patient-perceived needs, priorities, and expectations for health care. PCC, however, is still most often implemented from a traditional provider-centered, disease-focused framework that often results in patient care and outcomes that are not congruent with patients' preferences. Shifting to a model of care in which patients define their needs and priorities creates some unique issues in health care. Nursing, with its long-standing commitment to being patient focused, needs to lead the research effort to develop patient-centered models of care that consider and incorporate patients' preferences. Nurses must be mindful, however, of their socialization in the traditional model of care and the resulting underlying attitudes and assumptions they bring to their research and work with patients.

Mice lacking PKC gamma exhibit decreased anxiety.

To investigate the contribution of the PKC gamma isoform of protein kinase C (PKC) in neurochemical pathways regulating anxiety, mice lacking the gene encoding PKC gamma were tested with heterozygote and wild-type littermates in three approach-avoidance tests of anxiety. Null mutant mice consistently displayed a decrease in baseline anxiety-related behaviors in the elevated plus-maze, the black/white box, and the mirrored chamber. In the elevated plus-maze, mutant mice entered the open arms significantly more often and spent more time in the open arms of the maze. In the black/white box, transitions between the compartments were greatest in the null mutant mice, and in the mirrored chamber, mutant mice were markedly less anxious with significantly decreased latencies to enter and more time spent in the chamber. Indices of locomotor activity in the mazes and tests of activity in home cages indicated that the reduced anxiety observed in the mutant mice was not due to baseline locomotor activity differences among the genotypes. These results suggest that PKC gamma be considered as one factor in the etiology of anxiety, perhaps via its post-synaptic regulation of GABAA and 5-HT2 receptors, two receptors implicated in the neurobiology of anxiety.

Behavioural changes produced by transgenic overexpression of gamma2L and gamma2S subunits of the GABAA receptor.

Transgenic mice overexpressing either the mouse gamma2L or gamma2S subunit of the GABAA receptor were generated in a C57BL/6 J x DBA/2 J mixed background and expanded into transgenic lines. Transgenic mice and littermate controls were analysed with respect to altered behaviour indicative of anxiety, motor activity and acute effects of benzodiazepines and alcohol, as well as with regard to altered responses to alcohol withdrawal and acute functional tolerance to alcohol. Biochemical tests assessed flunitrazepam- and ethanol-enhanced 36Cl- flux stimulated by muscimol in cerebellar and cortical microsacs and [3H]-flunitrazepam binding to cerebellar membranes. There were no significant differences in any of these measures between the transgenic and control mice, except in tests of acute functional tolerance to acute injection of ethanol. Compared to controls, mice carrying either the gamma2L or gamma2S transgene developed significantly less tolerance to the ataxic effects of ethanol. We conclude that acute functional tolerance to ethanol is very sensitive to the amount of GABAA receptor gamma2 subunit available (regardless of whether it is gamma2L or gamma2S) but overexpression of neither subunit isoform alters other behavioural and biochemical phenotypes.

The relationship between staffing and quality in long-term care facilities: exploring the views of nurse aides.

Research on staffing and quality of care in long-term care facilities confirms that adequate staffing levels are important to ensuring quality but few studies have examined how the two are linked. The research reported in this article used participant observation and indepth interviewing to explore how nurse aides (NAs) understand the link between staffing and quality. The findings show that NAs deem their relationships with residents to be the central determinant of quality of care as well as an important outcome in itself. Adequate staffing is essential to allowing NAs to nurture these relationships.

Applications of transgenic and knockout mice in alcohol research.

Multiple genetic and environmental factors contribute to the development of alcoholism. Researchers attempting to elucidate the roles of specific genes in alcoholism risk have benefited from advances in genetic engineering. Two important tools used by researchers include transgenic mice, in which a foreign gene is integrated into an animal's genetic material, and knockout/knock-in mice, in which targeted genes either are rendered nonfunctional or are altered. Both of these animal models are currently used in alcohol research to determine how genes may influence the development of alcoholism in humans.

Background genotype modulates the effects of γ-PKC on the development of rapid tolerance to ethanol-induced hypothermia.

The role of γ-PKC in initial sensitivity and in the development of rapid tolerance to the hypothermic effects of ethanol were investigated in γ-PKC null mutant mice. Effects of the single gene mutation were evaluated on three different genetic backgrounds. Null mutants from a C57BL/6J X 129/SvJ mixed genetic background failed to develop rapid tolerance after 4 days of i.p. ethanol injections. However, when the null mutation was introgressed onto a C57BL/6J background for six generations to create a congenic line, the expression of rapid tolerance unexpectedly reoccurred in the null mutant mice. Subsequent outcrossing of the γ-PKC null mutation to a C57BL/6J X 129/SvEvTac mixed background did not restore the no tolerance phenotype. These observations, taken together with similar results reported previously concerning the development of chronic tolerance to ethanol in these same genotypes, ¹ indicate that the gene coding for gamma-PKC has pleiotropic effects in the expression of both rapid and chronic tolerance to ethanol-induced hypothermia. However, the impact of γ-PKC is modulated by the background genotype. These results stress the necessity of understanding interactions with genetic background when interpreting the effects of single gene mutations on complex behavioral traits.

Decreased ethanol sensitivity and tolerance development in gamma-protein kinase C null mutant mice is dependent on genetic background.

Initial sensitivity and tolerance development to the sedative-hypnotic and hypothermic effects of ethanol were investigated in gamma-protein kinase C (PKC) null mutant mice. Null mutants from a C57BL/6J x 129/SvJ mixed genetic background demonstrated decreased ethanol sensitivity and failed to develop chronic tolerance after 10 days of ethanol liquid diet. However, when the null mutation was introgressed onto a C57BL/6J background for six generations, the "no tolerance" phenotype for sedative-hypnotic and hypothermic effects of ethanol was no longer apparent Outcrossing the gamma-PKC null mutation to a C57BL/6J x 129/SvEvTac mixed background restored the "no tolerance" phenotype to ethanol-induced sedation after chronic ethanol diet; however, as measured by hypothermia, tolerance was still evident in the null mutant mice. These observations and the results of tests of chronic tolerance in the C57BL/6J, 129/SvJ, and 129/SvEvTac background inbred strains indicate that gamma-PKC plays an important role in initial sensitivity and tolerance to ethanol. However, the impact of gamma-PKC is modulated by the background genotype. These results stress the importance of including the effect of genetic background when evaluating the effects of single gene mutations on quantitative behavioral traits.

The use of null mutant mice to study complex learning and memory processes.

A number of neural substrates have been proposed to mediate complex learning and memory processes in mammalian organisms. One strategy for testing the involvement of a particular gene in learning and memory is to create a mouse line with a null mutation in that gene. Recently, embryonic stem cell-based gene-targeted homologous recombination techniques have been employed to create a number of such mutant mouse lines that do not express interesting candidate genes. These animals have been examined for impairments in several complex learning paradigms which are known to depend on the integrity of the hippocampus. In this review several complex learning and memory paradigms are described, the techniques to create null mutants are reviewed, and the results of recent studies with null mutants are described. Finally, the limitations for interpretation of behavioral data using null mutants are discussed.

Use of transgenics, null mutants, and antisense approaches to study ethanol's actions.

Behavioral and biochemical responses mediating ethanol's actions have been difficult to study in humans and animals because of their complex polygenic nature. Recent progress in the creation of new animal models using recombinant DNA technology has provided a set of genetic tools by which the role of specific candidate genes in ethanol's actions can be examined. These techniques include the creation of transgenic and null mutant mice, as well as manipulation of protein synthesis with antisense treatments. These techniques are reviewed, and their potential applications to alcohol research are discussed.