FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels.

The Intracellular Fibroblast Growth Factor (iFGF) subfamily includes four members (FGFs 11-14) of the structurally related FGF superfamily. Previous studies showed that the iFGFs interact directly with the pore-forming (alpha) subunits of voltage-gated sodium (Nav) channels and regulate the functional properties of sodium channel currents. Sequence heterogeneity among the iFGFs is thought to confer specificity to this regulation. Here, we demonstrate that the two N-terminal alternatively spliced FGF14 variants, FGF14-1a and FGF14-1b, differentially regulate currents produced by Nav1.2 and Nav1.6 channels. FGF14-1b, but not FGF14-1a, attenuates both Nav1.2 and Nav1.6 current densities. In contrast, co-expression of an FGF14 mutant, lacking the N-terminus, increased Nav1.6 current densities. In neurons, both FGF14-1a and FGF14-1b localized at the axonal initial segment, and deletion of the N-terminus abolished this localization. Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability.

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability.

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.

Maternal separation alters drug intake patterns in adulthood in rats.

Maternal separation/handling (MS/H) is an animal model of early life stress that causes profound neurochemical and behavioral alterations in pups that persist into adulthood. Many recent studies have used the MS/H model to study changes in drug effects in adulthood that are linked to behavioral treatments and stressors in the perinatal period. The drug effects focused on in this review are the reinforcing properties of the abused drugs, cocaine and alcohol. A striking finding is that variations in maternal separation and handling cause changes in ethanol and cocaine self-administration. Further, these changes indicate that various manipulations in the perinatal period can have long lasting effects of interest to biochemical pharmacologists. This article will review recent studies on ethanol and cocaine self-administration using the MS/H model and the neurochemical alterations that may play a role in the effects of MS/H on ethanol and cocaine self-administration. Studying the MS/H model can provide important clues into the vulnerability to drug abuse and perhaps identify a crucial window of opportunity for therapeutic intervention.

Spinal cord tissue affects ensheathing cell proliferation and apoptosis.

This study investigates proliferation and apoptosis of olfactory ensheathing cells in cocultures with spinal cord tissue. Proliferation of ensheathing cells was significantly increased when cocultured with explants from uninjured spinal cord, and spinal cord that had been subjected to chronic contusion or chronic needle stab injury, but not to acute needle stab injury. Proliferation rate was highest in cocultures with chronically stabbed cord tissue. Contaminating (p75NGFR-negative) cells in the cultures showed a significantly higher proliferation rate than ensheathing cells. Apoptosis of ensheathing cells was significantly increased in cocultures with acutely stabbed spinal cord explants compared with chronically contused spinal cord explants. These results suggest that delaying transplantation after spinal cord injury may be beneficial to ensheathing cell survival.

Implications of electronic health record meaningful use legislation for nursing clinical information system development and refinement.

PURPOSE: To describe what electronic health record meaningful use requirements mean for nursing clinical information system (CIS) development. CONCLUSIONS: The nursing CIS in many, if not most hospitals, has a number of critical design inadequacies that constrain the meaningful use of nursing data to ensure quality outcomes for patients and data-based maturing of the nursing profession. IMPLICATIONS: It is the responsibility and obligation of nurses to ensure that CISs are designed for the meaningful use of nursing clinical data. To accomplish these ends, interoperable clinical nursing data must be documented in a properly integrated operational CIS, and must be retrievable and stored in data repositories for analysis and reports.

Evaluation of outcome change scores for patients with pneumonia or heart failure.

This study was conducted to describe the variance in selected Nursing Outcomes Classification (NOC) outcome change scores of hospitalized older patients with pneumonia (n = 216) or heart failure (HF; n = 67) that could be explained by age, length of stay (LOS), number of comorbid conditions, number of nursing diagnoses, and number of nursing interventions. Investigators used a descriptive correlational design to analyze data sets from three U.S. community hospitals. Study participants had at least two ratings on one of nine outcomes selected for their frequency and use across the three hospitals. A significant portion of the variance in the outcomes Knowledge: Illness Care and Fall Prevention Behavior was explained for pneumonia patients. None of the regression models for HF patients showed significance. Individual independent variables were significant in some of the models (i.e., LOS [pneumonia], number of nursing diagnoses [pneumonia and HF]). Implications for research and clinical practice are discussed.

Most frequent nursing diagnoses, nursing interventions, and nursing-sensitive patient outcomes of hospitalized older adults with heart failure: part 1.

PURPOSE: Rank and compare the 10 most frequently documented nursing diagnoses, interventions, and patient outcomes using NANDA International, Nursing Interventions Classification, and Nursing Outcomes Classification for care of patients with heart failure (HF). METHODS: A descriptive comparative multisite study of documented care for 302 older adults with HF. FINDINGS: There were four common nursing diagnoses, two interventions, and only three common outcomes across three sites. CONCLUSIONS: This and similar analyses of clinical nursing data can be used by nursing administrators and clinicians to monitor the quality and effectiveness of nursing care. IMPLICATIONS: Similar analyses may be used for continuing education, quality improvement, and documentation system refinement. Part 2 will discuss data retrieval and implications for building a multiorganizational data warehouse.

Nursing clinical documentation data retrieval for hospitalized older adults with heart failure: part 2.

PURPOSE: The study aims to discuss the implications for retrieval of nursing data and building a multiorganizational data warehouse. METHODS: The method used was a descriptive comparative multisite study of documented care for 302 older adults with heart failure. Unit and patient level variables were retrieved. FINDINGS: Data regarding the most identified variables were retrievable electronically. Important linkages among nursing data elements were not present. CONCLUSIONS: Data were retrievable and the building of a data warehouse was possible and lessons were learned. IMPLICATIONS: When clinical information systems (CISs) are developed, developers and nurses must discuss how standardized data will be entered to ensure retrieval and usefulness in evaluating nursing care. For nursing effectiveness research, CISs must also provide linkages among nursing diagnoses and specific interventions, and nursing-sensitive patient outcomes.

Nursing diagnoses, interventions, and patient outcomes for hospitalized older adults with pneumonia.

A study was conducted by academic and community hospital partners with clinical information systems that included the standardized nursing language classifications of the North American Nursing Diagnosis Association International (NANDA-I), Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). The aim of the study was to determine the frequency of NANDA-I, NIC, and NOC (NNN) terms documented for older adults with pneumonia who were discharged from three hospitals during a 1-year period. NNN terms were ranked according to frequency for each hospital, and then the rankings were compared with previous studies. Similarity was greater across hospitals in rankings of NANDA-I and NOC terms than in rankings of NIC terms. NANDA-I and NIC terms are influenced by reimbursement and regulatory factors as well as patient condition. The 10 most frequent NNN terms for each hospital accounted only for a small to moderate percentage of the terms selected.

Intra-accumbal injection of CART (cocaine-amphetamine regulated transcript) peptide reduces cocaine-induced locomotor activity.

Evidence suggests that CART (cocaine-amphetamine regulated transcript) peptides are mediators or modulators of the actions of psychostimulant drugs. In this study, the effects of intra-accumbal injections of rat long form (rl) CART 55-102 were examined. Injection of the peptide alone had no effect, but pretreatment with the peptide blunted or reduced the locomotor-inducing effects of cocaine after an i.p. injection. This effect was dose related and time limited, as expected. rlCART 1-27, a CART peptide fragment not active in other studies, was without effect on cocaine-induced locomotor activity. Because the actions of cocaine involve dopamine, the effect of rlCART 55-102 on dopamine-induced locomotor activity was examined. Intraaccumbal injection of dopamine produced a dose-related and time-limited increase in locomotor activity, as expected. Coinjection of rlCART 55-102 with dopamine blunted the effect. In summary, these data suggest that CART peptides in the nucleus accumbens would tend to oppose the actions of cocaine.