Transient knock-down of kcna2 reduces sleep in larval zebrafish.

In the current study we set out to determine the effects of morpholino oligonucleotide (MO) knock-down of kcna2 on sleep-wake cycles in zebrafish. The results were compared to a non-overlapping MO injection, Dec2, who's mutant is also linked with a short sleep phenotype. Four groups of fish were used in the experiment: naïve fish, and fish injected with either control, kcna2, or Dec2 MO. All groups underwent 24-h behavioral monitoring of sleep-wake cycles at four and seven days-post-fertilization (dpf). First, we established an immobility dependent, sleep related, increase in arousal thresholds at both 4 and 7 dpf. Secondly, we show that kcna2 MO injected fish exhibit significantly less sleep behavior than controls and naïve fish, whereas Dec2 MO injections had similar but less severe effects. Finally, using kcna2 MO injected fish only, we turn to local field recordings at the level of the telencephalon and tectum opticum and rule out that the knock-down resulted in a non-specific increase in neural excitability that would mask sleep behavior.

Absence of rapid eye movements during sleep in adult zebrafish.

Sleep is not a uniform phenomenon, but is organized in alternating, fundamentally different states, rapid eye movement sleep and non-rapid eye movement sleep. Zebrafish (Danio rerio) have recently emerged as an excellent model for sleep research. Zebrafish are well characterized in terms of development, neurobiology and genetics. Moreover, there are many experimental tools not easily applied in mammalian models that can be readily applied to zebrafish, making them a valuable additional animal model for sleep research. Sleep in zebrafish is defined behaviorally and exhibits the hallmarks of mammalian sleep (e.g. sleep homeostasis and pressure). To our knowledge no attempts have been made to discern if sleep in zebrafish entails alternations of REM-NREM sleep cycles which are critical for further development of the model. In the current experiment we quantify two key REM sleep components, rapid eye movements and respiratory rates, across sleep-wake cycles. We find no sleep-related rapid eye movements. During sleep respiratory rates, however, are reduced and become less regular, further establishing that the behavioral definition used truly captures a change in the fish's physiology. We thus fail to find evidence for REM-NREM sleep cycles in zebrafish but demonstrate a physiological change that occurs concomitantly with the previously defined behavioral state of sleep. We do not rule out that other phasic REM components (e.g. atonia, cardiac arrhythmias, myoclonic twitches or desynchronized EEG) are coherently expressed during sleep but we conclude that adult zebrafish do not have REM-sleep-related rapid eye movements.

Translation and validation of two evidence-based nursing practice instruments.

BACKGROUND: Using existing instruments when assessing nurses' readiness for evidence-based practice facilitates comparison of research findings and adds to nursing knowledge in a global context. AIM: The study aims to: (1) translate the Information Literacy for Evidence Based Nursing Practice(©) (ILNP(©)) questionnaire and the Evidence-based Practice Beliefs Scale(©) (EBP Beliefs Scale(©)), (2) assess their appropriateness for use in Iceland, and 3) estimate the psychometric properties of the translated EBP Beliefs Scale [Icelandic-EBP Beliefs Scale (I-EBP Beliefs Scale)]. METHODS: The instruments were evaluated for appropriateness and relevancy before translation, and the ILNP(©) was modified to fit the Icelandic context. Translation followed recommended approaches, including back-translation. Pilot testing of both instruments ensued. A random sample of 540 nurses answered and returned the questionnaires. Reliability and validity of the I-EBP Beliefs Scale were tested on 471 complete I-EBP Beliefs Scale. Data were collected in 2007. RESULTS: The translated instruments demonstrated clarity and conciseness; however, the ILNP(©) needed to be further modified. For the I-EBP Beliefs Scale, Cronbach's α was 0.86 and Spearman-Brown r was 0.87. Principal components analysis supported the I-EBP Beliefs Scale's construct validity and unidimensional structure. Criterion validity was established by known-groups comparison (t-tests and one-way analyses of variance). CONCLUSIONS: The ILNP(©) and the EBP Beliefs Scale(©) can be used in contexts other than those for which they were developed. The I-EBP Scale is a psychometrically sound instrument and its performance supports the validity of the original scale. The instruments can be used to gather valuable information about nurses' readiness for evidence-based practice.

Spontaneous neural activity of the anterodorsal lobe and entopeduncular nucleus in adult zebrafish: a putative homologue of hippocampal sharp waves.

Spontaneous neural activity is instrumental in the formation and maintenance of neural circuits that govern behavior. In mammals, spontaneous activity is observed in the spinal cord, brainstem, diencephalon, and neocortex, and has been most extensively studied in the hippocampus. Using whole-brain in vitro recordings we establish the presence of spontaneous activity in two regions of the zebrafish telenchephalon: the entopeduncular nucleus (EN) and the anterodorsal lobe (ADL). The ADL is part of the lateral telencephalic pallium, an area hypothesized to be functionally equivalent to the mammalian hippocampus. In contrast, the EN has been hypothesized to be equivalent to the mammalian basal ganglia. The observed spontaneous activity is GABA modulated, sensitive to glutamate and chloride transporter antagonists, and is abolished by sodium pump blockers; moreover, the spontaneous activity in the ADL is a slow multiband event (∼100 ms) characterized by an embedded fast ripple wave (∼150-180 Hz). Thus, the spontaneous activity in the ADL shares physiological features of hippocampal sharp waves in rodents. We suggest that this spontaneous activity is important for the formation and maintenance of neural circuits in zebrafish and argue that applying techniques unique to the fish may open novel routes to understand the function of spontaneous activity in mammals.

The zebrafish brain in research and teaching: a simple in vivo and in vitro model for the study of spontaneous neural activity.

Recently, the zebrafish (Danio rerio) has been established as a key animal model in neuroscience. Behavioral, genetic, and immunohistochemical techniques have been used to describe the connectivity of diverse neural circuits. However, few studies have used zebrafish to understand the function of cerebral structures or to study neural circuits. Information about the techniques used to obtain a workable preparation is not readily available. Here, we describe a complete protocol for obtaining in vitro and in vivo zebrafish brain preparations. In addition, we performed extracellular recordings in the whole brain, brain slices, and immobilized nonanesthetized larval zebrafish to evaluate the viability of the tissue. Each type of preparation can be used to detect spontaneous activity, to determine patterns of activity in specific brain areas with unknown functions, or to assess the functional roles of different neuronal groups during brain development in zebrafish. The technique described offers a guide that will provide innovative and broad opportunities to beginner students and researchers who are interested in the functional analysis of neuronal activity, plasticity, and neural development in the zebrafish brain.

The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression.

This study examines the effects of transdermal nicotine patches for smoking cessation on depressive and withdrawal symptoms among 38 non-medicated subjects with Major Depressive Disorder. The study was conducted over a 29-day period, which included a 7 day baseline phase, a 14 day treatment phase, and an 8 day placebo phase. During the treatment phase subjects received either active nicotine patches (N = 18) or placebo patches (N = 20) that were administered in a randomized, double-blind fashion. The target quit date (TQD) was day 8. Significantly, more subjects in the placebo group than in the nicotine group resumed smoking following the TQD (50% vs. 22%). There was little evidence for effects of active nicotine patches on measures of mood (HRSD, BDI, POMS) or withdrawal symptoms among subjects that remained abstinent throughout the study (N = 24). Those who resumed smoking had more severe withdrawal symptoms than those who remained abstinent. One patient in the placebo group (n = 20) became more depressed after 2 weeks of abstinence. None of the patients in the nicotine group (n = 18) became more depressed.

Psychopharmacoepidemiology in Iceland: effects of regulations and new medications.

The sale of psychotropic medications in Iceland has waxed and waned during the past 20 years with approximately 5 years between peak and bottom quantities sold. Apparently, it has decreased following restrictions imposed by the public health authorities and increased again following the introduction of new drug. In order to study this further, all prescriptions for psychotropic medications to non-hospitalized inhabitants of the capital city (Reykjavík) and dispensed by pharmacists there during 1 month in 1984, 1989 and 1993 were analysed in order to estimate the 1-month prevalence of psychopharmacological use. The results support the hypothesis partly as prescriptions for tranquillizers decreased in 1989 as well as the amount of tranquillizers and hypnotics prescribed following new restrictions, whereas the prevalence odds ratio of obtaining prescriptions for hypnotics remained unchanged. The proportion of patients receiving excessive amounts of tranquillizers and/or hypnotics decreased. The prevalence of excessive use of these drugs (i.e. > 90 DDD/month) was 0.5% in 1993. In 1993 the prevalence of the use of antidepressants as well as the amount prescribed had increased substantially following the introduction of the new selective serotonin reuptake inhibitor medications. Thus, the prevalence of patients obtaining any psychotropic medication remained unchanged from 1984 to 1993.

Clinical implications of IgA rheumatoid factor subclasses.

OBJECTIVES: To evaluate the diagnostic and pathogenetic significance of IgA rheumatoid factor (RF) subclasses in rheumatoid arthritis (RA). METHODS: Rheumatoid factors of the IgA class and IgA1 and IgA2 subclasses were measured by enzyme linked immunosorbent assay in 58 patients with RA, 31 patients with other rheumatic diseases, 30 non-rheumatic individuals with increased concentrations of IgA RF, and in 100 randomly selected healthy controls. RESULTS: Using a 95% cut off for the controls, 55% of the RA patients had increased total IgA RF, 64% IgA1 RF, and 60% IgA2 RF. RA patients with extraarticular manifestations more often had increased concentrations of IgA RF and both subclasses than patients without such manifestations (p < or = 0.01). Nearly all (31/32) RA patients with increased IgA RF had increases in both IgA RF subclasses, compared with 67% (20/30 of nonrheumatic symptom free individuals with increased IgA RF (p = 0.002). CONCLUSION: Increased concentrations of the IgA2 RF subclass appears to be more specific for RA than increased IgA1 RF. Measurement of IgA RF subclasses may be clinically useful.

Tolerance of ciprofloxacin at injection site, systemic safety and effect on electroencephalogram.

The safety of ciprofloxacin, given via 30- and 60-min intravenous infusions at a dose of 300 mg every 12 h for 4 days, was studied in 12 healthy subjects (6 females, 6 males). Local effects of the drug were assessed by frequent examination at the infusion site while systemic safety was determined by haematological and biochemical tests and by careful microscopic examination of the urine for drug crystals and by electroencephalographic studies performed in all subjects before and after dosing. At the site of infusion erythema, itching and a burning sensation developed 10-15 min after onset of infusion in some subjects. These symptoms were slight and did not necessitate termination of the infusions. The rash disappeared in some instances during the infusion and in others within minutes after the end of infusion. The changes usually disappeared, even during the infusion. The incidence of the adverse reactions was not related to the duration of the infusion (30 or 60 min), but was less (frequency and extent) when the anticubital vein was used for infusion rather than when smaller more peripheral veins were employed. Thrombophlebitis occurred after 1 of 96 administrations, and was followed by a return to normal. The electroencephalograms remained normal in all instances. One subject experienced mild nausea of a few hours duration. Only 1 volunteer showed crystalluria; the two such specimens from this subject had the most alkaline pH of all urine samples collected in this study. The probability of crystalluria upon intravenous administration appears not to be higher than after oral administration of ciprofloxacin.