GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus.

Development of the neuronal circuitry involves both Hebbian and homeostatic plasticity mechanisms that orchestrate activity-dependent refinement of the synaptic connectivity. AMPA receptor subunit GluA4 is expressed in hippocampal pyramidal neurons during early postnatal period and is critical for neonatal long-term potentiation; however, its role in homeostatic plasticity is unknown. Here we show that GluA4-dependent plasticity mechanisms allow immature synapses to promptly respond to alterations in network activity. In the neonatal CA3, the threshold for homeostatic plasticity is low, and a 15-h activity blockage with tetrodotoxin triggers homeostatic upregulation of glutamatergic transmission. On the other hand, attenuation of the correlated high-frequency bursting in the CA3-CA1 circuitry leads to weakening of AMPA transmission in CA1, thus reflecting a critical role for Hebbian synapse induction in the developing CA3-CA1. Both of these developmentally restricted forms of plasticity were absent in GluA4(-/-) mice. These data suggest that GluA4 enables efficient homeostatic upscaling and responsiveness to temporal activity patterns during the critical period of activity-dependent refinement of the circuitry.

Identifying Critically Ill Veterans Who Require Nutrition Intervention: A Quality Improvement Study Comparing Nutrition Risk Tools.

BACKGROUND: Identification of intensive care unit (ICU) patients who require nutrition intervention is crucial to initiating nutrition therapy. This prospective quality improvement study evaluated the Nutritional Risk Screening (NRS) 2002, Malnutrition Universal Screening Tool (MUST), and Nutrition Risk in Critically Ill (NUTRIC) score in comparison with the Veterans Administration Nutrition Status Classification (VANSC) tool to determine which best identified the need for nutrition intervention. METHODS: A convenience sample of 150 ICU patients was evaluated using the VANSC, NRS 2002, MUST, and the NUTRIC score. The resultant score, need for nutrition intervention, and presence of malnutrition were recorded for patients. Interventions were defined as need for enteral or parenteral nutrition, nutritional supplements, or diet change. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Matthews Correlation Coefficient (MCC), F1 score, and accuracy to predict need for nutrition intervention were calculated for each screening tool. RESULTS: Of the 150 patients, 49 (33%) required 1 or more nutrition interventions. The NRS 2002 (0.878) and VANSC (0.816) had the highest sensitivity. The NUTRIC (0.921) and VANSC (0.911) had the highest specificity. The VANSC (0.816) and MUST (0.687) had the highest PPV. The VANSC (0.911) and NRS 2002 (0.872) had the highest NPV. The VANSC (0.727) and MUST (0.528) had the highest MCC. The VANSC (0.816) and MUST (0.680) had the highest F1 score. CONCLUSIONS: Trialing several tools to identify their efficacy and reliability individual setting may help determine the most appropriate tool to utilize for your patient population and specific goals.

A critical role of a facilitatory presynaptic kainate receptor in mossy fiber LTP.

The mechanisms involved in mossy fiber LTP in the hippocampus are not well established. In the present study, we show that the kainate receptor antagonist LY382884 (10 microM) is selective for presynaptic kainate receptors in the CA3 region of the hippocampus. At a concentration at which it blocks mossy fiber LTP, LY382884 selectively blocks the synaptic activation of a presynaptic kainate receptor that facilitates AMPA receptor-mediated synaptic transmission. Following the induction of mossy fiber LTP, there is a complete loss of the presynaptic kainate receptor-mediated facilitation of synaptic transmission. These results identify a central role for the presynaptic kainate receptor in the induction of mossy fiber LTP. In addition, these results suggest that the pathway by which kainate receptors facilitate glutamate release is utilized for the expression of mossy fiber LTP.

Fast network oscillations in the newborn rat hippocampus in vitro.

Spontaneous neural activity is crucial for the formation of the intricate patterns of cortical connectivity during development. In particular, temporal correlations in presynaptic and postsynaptic activity have been hypothesized to be a critical determinant in the selection of neurons that are to become wired together. To date, however, temporally correlated activity in the neonatal brain has been believed to take place with a precision of tens of milliseconds to seconds. Here we describe a novel type of a fast network oscillation associated with millisecond synchronization of pyramidal cell firing in newborn rat hippocampus in vitro. Individual pyramidal neurons fired mainly at lower gamma frequencies (20-40 Hz) but were synchronized into a high-frequency (100-400 Hz) population oscillation that was reflected in field potential spikes and intracellular AMPA-kainate receptor-mediated currents. The high-frequency population oscillation was patterned by a gamma-frequency modulatory oscillation. The gamma modulation was imposed by GABAergic currents, which exerted an inhibitory action on pyramidal neurons. Patterned activity based on GABAergic inhibition and glutamatergic excitation thus occurs already in newborn hippocampus. The network oscillations described here may be a mechanism for selective coincidence detection with a millisecond range temporal precision to shape the patterns of connectivity within the emerging hippocampal synaptic circuitry.

A novel beta-N-acetylglucosaminidase activity in hog gastric mucosal microsomes: preferential hydrolysis of terminal GlcNAc beta 1-3 linkages in GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc, but GlcNAc beta 1-6 linkages in GlcNAc beta 1-3(GlcNAc beta 1-6)Gal.

Hog gastric mucosal microsomes contain beta-N-acetylglucosaminidase activity which cleaves GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc at the terminal GlcNAc beta 1-3Gal linkage faster than at the GlcNAc beta 1-6Gal bond, producing mainly GlcNAc beta 1-6Gal beta 1-4GlcNAc. In a marked contrast, GlcNAc beta 1-3(GlcNAc beta 1-6)Gal is cleaved primarily at the GlcNAc beta 1-6Gal bond, while partial hydrolysis of GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4Glc reveals similar rates of cleavage for the (1-3) and (1-6) linkages. Our data support the notion that the terminal beta 1,6-linked GlcNAc unit of GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc may interact with the reducing end GlcNAc unit intramolecularly in water solution.

The beta 1,6-GlcNAc transferase activity present in hog gastric mucosal microsomes catalyses site-specific branch formation on a long polylactosamine backbone.

We find that the beta 1,6-GlcNAc transferase activity present in hog gastric mucosal microsomes converts the linear pentasaccharide GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc (1) in a site-specific way to the branch-bearing hexasaccharide GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc (2). The product is a positional isomer of GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc (3), reportedly formed from 1 by another polylactosamine beta 1,6-GlcNAc transferase activity present in human serum (Leppänen et al., Biochemistry, 30 (1991) 9287). Combined use of the two kinds of activities gave in the present experiments the heptasaccharide GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc (4), in which one of the branches occupies the position of the branch in 2 and the other the position of the branch in 3.

Synaptic activation of a presynaptic kainate receptor facilitates AMPA receptor-mediated synaptic transmission at hippocampal mossy fibre synapses.

The development of GluR5-selective kainate receptor ligands is helping to elucidate the functions of kainate receptors in the CNS. Here we have further characterised the actions of a GluR5 selective agonist, ATPA, and a GluR5 selective antagonist, LY382884, in the CA3 region of rat hippocampal slices. In addition, we have used LY382884 to study a novel synaptic mechanism. This antagonist substantially reduces frequency facilitation of mossy fibre synaptic transmission, monitored as either AMPA or NMDA receptor-mediated EPSCs. This suggests that GluR5-containing kainate receptors on mossy fibres function as autoreceptors to facilitate the synaptic release of L-glutamate, in a frequency-dependent manner.

Post-insult activity is a major cause of delayed neuronal death in organotypic hippocampal slices exposed to glutamate.

We investigated the pathophysiological mechanisms of glutamate-induced delayed neuronal damage in rat hippocampal slice cultures [Stoppini et al. (1991) J. Neurosci. Methods 37, 173-182], with propidium iodide as a marker of cell death. Exposure of the cultures to growth medium containing 10 mM glutamate for 30 min resulted in a slowly developing degeneration of hippocampal principal cells, starting from the medial end of the CA1 region and reaching the dentate gyrus by 48 h. By 24 h, most pyramidal cells in CA1 were damaged. An acute phase of degeneration preceded the delayed damage at 2-6 h, affecting cells in a spatially diffuse manner. When tetrodotoxin (0.5 microM) was present during the glutamate insult, a marked protection (mean 57%, P<0.001) of the CA1 damage was observed. Rather strikingly, when tetrodotoxin was applied immediately following or even with a delay of 30 min after the insult, a similar amount of protection was achieved. In field recordings carried out after the insult, the glutamate-treated slices exhibited spontaneously occurring negative shifts with a duration of 1-10 s and an amplitude of up to 400 microV in the CA3 region, whereas the control slices were always quiescent. Taken together, the results suggest that post-insult neuronal network activity, rather than the direct action of exogenous glutamate, is a major cause of delayed CA1 pyramidal cell death in the organotypic slices. These observations may have implications in the design of neuroprotective strategies for the treatment of brain traumas which are accompanied by delayed and/or distal neuronal damage.

High-frequency synaptic stimulation induces association of fyn and c-src to distinct phosphorylated components.

Signaling via tyrosine kinases appears necessary for regulation of synaptic efficacy. Interactions of the src-family kinases with phosphorylated proteins were studied in area CAI of rat hippocampal slices 10 min after induction of long-term potentiation (LTP) by 100 Hz/l s stimulation (HFS). HFS enhanced association of the src-family kinases fyn and c-src with an approximately 120 kDa tyrosine phosphorylated component containing the focal adhesion kinase (FAK) and its homologue PYK2. Association of fyn with FAK and of c-src with PYK2 was increased following the HFS. Further, increase in tyrosine phosphorylation of PYK2 was detected following the HFS. These results suggest that fyn and c-src are involved in distinct signaling pathways and provide evidence for activation of FAK and PYK2 following synaptic stimulation inducing LTP in vitro.

Activity-induced enhancement of HB-GAM expression in rat hippocampal slices.

Heparin-binding growth-associated molecule (HB-GAM) is a developmentally regulated secretory protein with neurite outgrowth-promoting activity. High-frequency stimulation leading to induction of long-term potentiation (LTP) resulted in increased expression of HB-GAM in rat hippocampal area CA1. When tetanization was given in the presence of antagonists of the N-methyl-D-aspartate (NMDA) receptor and postsynaptic voltage-gated calcium channels, the mRNA level was comparable to control levels. The results indicate that high frequency stimulation inducing LTP results in calcium-dependent enhancement in HB-GAM expression, and imply a role for this extracellular protein in the modulation of synaptic function in the hippocampus.

Nurses' knowledge about pharmacological and nonpharmacological pain management in children.

The purpose of this study was to investigate the knowledge base and practices of Finnish nurses in the area of children in pain. The convenience sample consisted of 265 nurses working on children's wards in university hospitals. Data were collected using an instrument designed for the study. The results showed that there remain gaps in the knowledge base of nurses with regard to both pharmacological and nonpharmacological pain management in children. The education and the area of expertise were significant influences on knowledge scores. Nurses used a fairly wide range of nonpharmacological pain alleviation methods but most of these were such that the nurse was in an active role and the child was passive. There is a clear need for further education. Nurses should take a more active role in seeking new information and also should be encouraged to use nonpharmacological methods that let the children be active participants in their own care.

Security associated with pregnancy and childbirth--experiences of pregnant women.

The aim of this study was to describe security associated with pregnancy and childbirth. Security was described as a human need and as human value. Data were collected in semi-structured interviews in two maternity health care clinics. Data interpretation was based on the method of content analysis. A convenience sample of 20 volunteer Finnish women was interviewed during pregnancy. The elements creating security associated with pregnancy and childbirth were maternity health care, social support, sense of control, and attitudes. The feeling of security was manifested in different resources, feelings and behavior. If the feeling of security associated with pregnancy and childbirth was impaired, the participants would resort to their network of social support, contact health care or social welfare services, or try to achieve a sense of security by their own resources. Feeling secure during pregnancy influences the pregnant woman's resources, feelings and behavior. It is important that professionals in maternity health care talk with the client about issues that influence her individually-experienced security associated with pregnancy and childbirth. These include examination of the client's network of social support and informing the client about the health care and social welfare services available.

Cancer patients' reported experiences of suffering.

This study describes the nature and content of experiences of suffering by patients with incurable cancer. The main body of data was collected in interviews. A structured questionnaire was administered for additional information. Three different dimensions were identified in patient experiences of suffering: physical, psychologic, and social. Suffering has a physical foundation, which was divided into two categories: that caused by the illness itself and that caused by treatment of the illness. The primary sources of physical suffering were fatigue, pain, and the side effects of chemotherapy. The causes of psychologic suffering lie in the physiologic changes associated with the disease and in the imminence of death. Psychologic suffering was most typically manifested in depression, which most of the patients suffered during the initial stages of the disease, when the disease metastasized, and when they were in a particularly poor condition. General deterioration and fear of infections very much restrict the social life of cancer patients, causing them to withdraw into their home or the hospital.

How relatives adjust after the death of a patient with cancer in hospice.

This study aims to discover (1) how relatives adjust to their new life situations following the death of a patient with cancer in hospice and (2) how those relatives have been supported by healthcare professionals both before and after the patient's death. The data were collected with a structured questionnaire administered to relatives of patients with cancer who died in a Finnish hospice in 1998 and 1999. The questionnaires were administered by the hospice staff to all family members who met the criteria specified (n = 589). The final sample comprised 258 family members, most of whom were the deceased patients' spouses. The Mann-Whitney U-test and the Kruskal-Wallis test were used to analyze the data. Instrument reliability was ascertained by the Cronbach alpha coefficient. The relatives had little difficulty accepting their new life situation and adjusting to their new role. The main factors affecting adjustment were being the patient's spouse and the age of both patient and relative. Relatives believed that they received a moderate amount of support from healthcare professionals, both before and after the patient's death. Most of the information they received concerned the patient's illness and treatment and daily condition. Communication was honest and based upon the relatives' needs. Emotional support before the patient's death consisted mainly of accepting the relative and listening to what relatives had to say.

Patient participation in decision making about care.

The purpose of this study was to find out how cancer patients perceive patient participation in decision-making and to see which factors in their view facilitate and restrict participation. Data were collected in focus group interviews with 25 patients, most of whom had breast cancer. Data interpretation was based on the method of qualitative content analysis. The results showed that patients, nurses and physicians all play a part in terms of how patients participate in decision-making. Patients defined participation in decision-making in terms of asking questions, obtaining/providing information and choosing from/presenting different alternatives. Among the factors that were thought to promote participation in decision-making were the patient's activity, the presence of a primary nurse/physician, the encouragement of nurses and physicians to participate, the treatment of patients as equals, and nurses and physicians having enough time for patients. As for factors hindering participation in decision-making, reference was made to patient ignorance, physical and mental imbalance and shyness on the part of the patient. Obstacles to participating in decision-making that originated in the nurses and physicians were the tendency for them to treat patients as objects, to fall in a routine, problems with information dissemination and lack of time.

Attitudes of patients with breast and prostate cancer toward complementary therapies in Finland.

This study aimed to describe the attitudes of patients with breast cancer and those with prostate cancer toward complementary therapies. The data were collected with a postal questionnaire administered to 216 patients with breast cancer (response rate, 55.4%) and 1 90 patients with prostate cancer (response rate, 54.9%) in southern and southwestern Finland. The questionnaire was composed of 44 Likert-type statements, which were analyzed using descriptive statistics, chi2 tests, t tests, and two-way analyses of variance. More than half (54%) of the patients with breast cancer and 45% of the patients with prostate cancer believed that people with cancer may benefit from complementary therapies, although they did not think these therapies actually could cure cancer. More than half of the respondents were dubious about using complementary therapies as long as there was no solid scientific evidence. Most believed that complementary therapies were used because they gave people hope (women, 88%; men, 72%) or "something to cling to" (women, 83%; men, 76%). The respondents believed most in dietary therapies and least in healing. There was much confusion and uncertainty about the professional competencies and expertise of the people who provided complementary therapies. Approximately one fourth of the respondents had spoken to their physician about complementary therapies. Only a few had talked about the matter with nursing staff. About half of the respondents thought that physicians and nurses took a negative attitude toward complementary therapies. In both groups, patients who had talked with their physician about complementary therapies tended to show a more positive attitude.

Ethical reasoning associated with the feeding of terminally ill elderly cancer patients. An international perspective.

An international nursing research study examined the ethical decision-making of "good and experienced" registered nurses in eight countries. The subjects were asked about their decision to feed or not to feed a hypothetical terminally ill, mentally alert, elderly cancer patient who refuses to eat. Cultural variations were demonstrated in the decisions as well as differences in ethical justification. The majority of nurses who would not feed appeared to use the principle of autonomy, whereas nurses who would feed the patient used beneficence as justification. Conditions under which nurses would change their decision to either feed or not feed the patient against her will included doctor's orders and lack of peer support for the decision. The majority of nurses clearly experienced a dilemma.

Decision making of nurses practicing in intensive care in Canada, Finland, Northern Ireland, Switzerland, and the United States.

In this study, our intention was to describe the decision making of nurses practicing in intensive care, and the differences of nurses' decision making in Canada, Finland, Northern Ireland, Switzerland, and the United States. The instrument used in the study was a 56-item Likert-type questionnaire that has been used in previous studies and has proved to be a reliable tool. The target group comprised a nonrandom sample of nurses (N = 314) from five countries. The samples are not representative; therefore, the results in these cases cannot be generalized. The results showed that the decision making of nurses practicing in intensive care was broadly based, and that there were some country differences in data collection, problem definition, and planning. In contrast, decision making related to the implementation and evaluation of nursing is quite similar in the different countries. Canada and the United States on the one hand, and Finland, Northern Ireland, and Switzerland on the other, showed more similarities with each other in data collection, problem definition, and nursing planning related to decision making. Neither experience nor nurse's knowledge structure was associated with different decision-making approaches.

Patient's and general practitioner's different views on patient's depression.

Differences between patient's and general practitioner's view on patient's depressive syndromes was investigated in a prospective birth cohort study of 70 year old people (n=1032) in Turku City, Finland. The aim of this study was to find factors which are typical for people having depressive syndromes in old age and help medical and nursing staff to identify depressive syndromes in the general aged people. The study consisted of a structural postal questionnaire including patient's perception of his depression, an interview made by a public health nurse included mini-mental state examination (MMSE) and the self-rating depression scale of Zung, an interview and comprehensive clinical examination by a general practitioner. Out of the 847 persons who completed the depression test, 12.6% showed symptoms of depressive syndrome. The views of those who scored more than 45 points in the Zung depression scale on their own depressiveness differed from the general practitioner's opinion. In the general practitioner's examination and interview 58% of the subjects had no depressive symptoms even though the test results indicated that they were depressed. The depressed group stood out most clearly in two questions: Do you feel you are needed and do you have future plans? When the same questions were repeated 5 years later, the difference was still statistically significant between depressed and non-depressed group (P<0.0001). The data indicated that medical and nursing staff should take self-assessments seriously and look into them in closer detail. General practitioners and nurses should learn to ask right questions and use short depression scale systematically in order to facilitate the detection of depressive syndromes.

Fears associated with pregnancy and childbirth--experiences of women who have recently given birth.

OBJECTIVE: To describe fears associated with pregnancy and childbirth and to see whether women who have recently given birth feel that their fears were justified. DESIGN: A qualitative study. Data were collected by semi-structured interviews. Data interpretation was based on the method of content analysis. SETTING: The maternity units of two university hospitals in Finland. PARTICIPANTS: A convenience sample of 20 women, 10 primiparae and 10 multiparae. The interviews were held 2 or 3 days after childbirth. FINDINGS: The most common fears associated with pregnancy and childbirth were concerned with the baby's well-being, the course of pregnancy, and childbirth. The fears found expression in different kinds of behaviours, emotions and physical sensations. Many of the participants felt that their fears had not been justified, but some maintained that their fears had been justifiable. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: There was much inter-individual variation in the fears associated with pregnancy and childbirth. It is important that diagnosis during pregnancy is undertaken sensitively and that midwifery staff remember that pregnant women may have very serious fears associated with pregnancy and childbirth. The participants in this study felt that fears associated with pregnancy and childbirth also had positive meanings. It may not be essential to try to protect women against these fears or to remove them altogether, but to give every pregnant women the opportunity to deal with her own fears and to obtain the help she needs in her situation.