Nationwide strike in Ireland looks inevitable.
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Humans↗
Biomedical subjects
K Williams
Publications and source records attributed to K Williams.
Former colleagues defend Saudi murder suspects.
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England↗
Communicable diseases and the Australian Paediatric Surveillance Unit.
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Australia↗
Shoaling generates social learning of foraging information in guppies
Two experimental studies are reported which investigate the social learning of foraging information in guppies, Poecilia reticulataIn both cases, untrained adult female guppies swam with trained conspecifics to feed, and in the process learned a route to a food source. In experiment 1, subjects were given 5 days experience swimming with demonstrator fish trained to take one of two equivalent routes to food. When tested alone, subjects preferentially used the route of their demonstrators. Experiment 2 investigated whether this social learning could mediate the stable transmission of route preferences among small populations of fish. This experiment used a transmission chain design, in which fish in small founder populations were trained to take one of the two routes, with founder members gradually replaced by untrained conspecifics. Three days after all founder members had been removed, populations of untrained fish still maintained strong preferences for the routes of their founders. The results suggest that the tendency to shoal may facilitate a simple form of guided social learning, which allows guppies to learn about their local environments. They also imply that selectively neutral behavioural alternatives may be maintained as traditions in aggregated animal populations by very simple social mechanisms. The transmission chain method may be particularly useful for studying social species, such as the guppy, that do not respond well to isolation testing.
Journal Article↗
Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group.
A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.
Adult↗
Puberty influences expression of phospholipid hydroperoxide glutathione peroxidase (GPX4) in rat testis: probable hypophysis regulation of the enzyme in male reproductive tract.
Mammalian spermatozoa are unusually rich in polyunsaturated fatty acids, a property that predisposes them to the deleterious effects of oxygen free radicals. Mouse and human spermatozoa utilize glutathione peroxidase, (GPX), to inactivate oxygen free radicals. In the GPX super-family there is the enzyme phospholipid hydroperoxide glutathione peroxidase (GPX4) that specifically protects membrane phospholipids against peroxidation. GPX4 is present, primarily, in testis where its enzymatic activity seems to be present only after puberty. In order to clarify this question we utilized total RNA from rat testis, liver and lung to carry out cDNA synthesis and the following RT-PCR amplification of cDNA products by using specific primers of rat liver sequence. RT-PCR products of the expected size for GPX4 (525 bp) were obtained from the three tissues. At last, these fragments were submitted to sequencing analysis. Here we demonstrate that the sequence analysis of rat testis GPX4 coding region is identical to that of rat liver and lung; however puberty influences the expression pattern of rat testis GPX4. In fact Northern blot analysis of total RNA from normal and pre-puberal hypophysectomized rats demonstrates the absence of a specific GPX4 mRNA in total RNA from pre-puberal hypophysectomized rat testis; on the other hand this specific transcript is present in both normal rat testis and liver and in pre-puberal hypophysectomized rat liver. Expression pattern of GPX4 is very low in lung both in post-puberal and pre-puberal hypophysectomized rats. Therefore hypophysis could regulate GPX4 transcript in rat testis.
Amino Acid Sequence↗
Dynamic mechanical thermal analysis of maxillofacial elastomers.
STATEMENT OF PROBLEM: Maxillofacial prosthetic materials should simulate the oral tissues as much as possible and therefore have a similar flexibility and resilience. In light of the oral tissues constantly moving, the dynamic deformation properties of maxillofacial materials would seem the most relevant. PURPOSE: In this study, dynamic mechanical thermal analysis was used to evaluate the deformation properties of five silicone rubber materials used to construct facial prostheses. The technique involves the application of a sinusoidally oscillating stress to a material and analyzes how the material elastically or viscoelastically responds to the stress. The dynamic mechanical thermal analysis can operate at a fixed frequency or range of frequencies over a specific temperature range and also isothermally as a function of time. RESULTS: Cosmesil and A-2186 materials were the most resilient materials and Silbione had the greater energy absorption capacity, which was particularly noticeable at the higher frequencies. Silbione also had a lower shear modulus (G'), which indicated it was more flexible than the other materials. CONCLUSION: The dynamic mechanical thermal analysis proved to be a rapid, reliable, and convenient method for the determination of viscoelastic properties of maxillofacial materials.
Analysis of Variance↗
Modulation and block of ion channels: a new biology of polyamines.
The endogenous polyamines, spermine, spermidine, and putrescine have effects on several types of cation channels. Intracellular polyamines, in particular spermine, contribute to intrinsic gating and rectification of strong inward rectifier K+ channels. Intracellular spermine is also responsible for inward rectification of some types of Ca(2+)-permeable AMPA and kainate receptors. Spermine has a number of effects on the activity of the NMDA subtype of glutamate receptor, involving two or more extracellular polyamine binding sites on the NMDA receptor. In K+ channels and glutamate receptors, some of the amino acids in the receptor/channel structure that influence to polyamines have been identified, leading to a partial understanding of the effects of polyamines at a molecular level. Block of K+ channels by intracellular polyamines is likely to be an important receptors by intracellular spermine and modulation by extracellular spermine may affect excitability and the influx of Ca2+ in neurons and glial cells of the nervous system.
Animals↗
Conserved features of TBE1 transposons in ciliated protozoa.
The complete sequences of four TBE1 transposons from Oxytricha fallax and O. trifallax are presented and analyzed. Although two TBE1s are 98% identical to each other at the nucleotide level, the remaining two TBE1s are only 90% identical both to each other and to the other two. This large evolutionary divergence allows us to identify conserved TBE1 features. TBE1 transposons are 4.1 kbp long and are flanked by 3 bp target-site repeats. The elements consist of 78 bp inverted terminal repeats, of which the 17 terminal base pairs are Oxytricha telomere repeats; a central conserved section of 550 bp that includes a set of nested direct and inverted sequence repeats; and 3 open reading frames conserved for encoded amino acid sequence. The three open reading frames encode a 22 kDa basic protein of unknown function, a 42 kDa 'D,D35E' transposase, and a 57 kDa chimeric C2H2 zinc finger/protein kinase. The protein kinase domain of the 57 kDa protein is unusual, lacking a conserved ATP-binding motif.
Amino Acid Sequence↗
Preventing suicide in young people: what is known and what is needed.
In the UK the suicide rate for male adolescents has nearly doubled since 1975. With a similar increase reported from other countries it is not surprising that preventing suicide in young people has become a priority for many health professionals and policy makers. Unfortunately despite advances in our understanding of suicide in young people there are still deficiencies and inconsistencies in our knowledge. There are also problems in transforming our knowledge of suicide and suicidal behaviour in young people and our understanding of theoretically possible approaches to prevention into effective suicide prevention strategies. To increase the chance of preventing suicide in young people we need to be aware of the problems of putting theory into practice and evaluate all interventions that are undertaken to determine their appropriateness and effectiveness.
Adolescent↗
Using research for practice: a UK experience of the BARRIERS Scale.
It is generally recognized that the majority of health care has been largely based upon opinion rather than research evidence of clinical effectiveness. Attempts to rectify this have been initiated by increasing emphasis on the dissemination of findings. For example, in the UK this had been supported via the Cochran Collaboration and the Centre for Dissemination and Reviews. Dissemination does not, however, guarantee implementation. The complex nature of research utilization has been studied and obstacles identified that can influence the uptake of research by practising nurses. Sandra Funk and colleagues developed the BARRIERS Scale using this research and literature on research utilization. The scale may be helpful for identifying and measuring the barriers to research utilization perceived by nurses working within the UK and has formed the basis of the present study. A convenience sample of 316 comprising a broad spectrum of nurses working in the UK provided the data. Comparison is made with North American nurses from the studies used in the scale's development. The results suggest there ware items which are consistently perceived as either strong or negligible barriers by both groups of nurses. Differences, however, did emerge between nurses from the UK and North America on several items. These included the confidence in evaluating research and the perception of the nurse's authority to change patient procedures. Psychometric evaluation was also done. These findings are presented and discussed.
Cross-Cultural Comparison↗
From university to community: the Baton Rouge experience.
This paper describes a successful hepatitis B vaccination program which expanded from one school vaccinating 475 students to 68 schools vaccinating 3,400 students. Issues associated with success include acquiring resources, organizing program logistics, developing an advisor board, determining eligibility for free vaccine, obtaining vaccine for those not eligible for publicly supplied vaccine, methods of consenting, and managing data. The process of obtaining support can increase public awareness and assist further program expansion. The program demonstrates that the time and energy expended in start-up activities for the first two or three years will evolve into a program with a life of its own, requiring only a moderate amount of attention while generating strong positive community support.
Adolescent↗
N1-dansyl-spermine and N1-(n-octanesulfonyl)-spermine, novel glutamate receptor antagonists: block and permeation of N-methyl-D-aspartate receptors.
The effects of several N-sulfonyl-polyamines, including N1-dansyl-spermine (N1-DnsSpm) and N1-(n-octanesulfonyl)-spermine (N1-OsSpm), were studied at recombinant N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus laevis oocytes. N1-DnsSpm and N1-OsSpm inhibited NMDA receptors and were approximately 1000-fold more potent than spermine in oocytes voltage-clamped at -70 mV. Block by N1-DnsSpm and N1-OsSpm was strongly voltage dependent, being more pronounced at hyperpolarized membrane potentials. With the Woodhull model of voltage-dependent channel block, the values of Kd(0) were 779 microM, 882 microM, and 7.4 mM and those of z delta were 2.58, 2.57, and 1.07 for N1-DnsSpm, N1-OsSpm, and spermine, respectively. This suggests that an increase in the voltage dependence of block together with an increase in affinity contributes to the increased potencies of N1-DnsSpm and N1-OsSpm compared with spermine. Sensitivity to N1-DnsSpm was reduced by mutation NR1(N616Q) and was increased by mutations NR1(N616G) and NR2A(N615G). The NR1(N616G) and NR2A(N615G) mutations decreased the Kd(0) value of N1-DnsSpm without affecting z delta, whereas the NR1(N616Q) mutation reduced z delta. These mutations may alter the accessibility of part of the polyamine binding site within the channel pore or directly alter the properties of that site. Block by N1-DnsSpm (0.3 microM) was almost complete at -100 mV, and there was no relief of block at extreme negative membrane potentials (-100 to -200 mV) at wild-type NR1/NR2A channels. In contrast, block by N1-DnsSpm was partially relieved at extreme negative potentials at receptors containing NR1(N616G) or NR2A(N615G), suggesting that N1-DnsSpm can permeate these mutant channels but not wild-type NR1/NR2A channels. This is hypothesized to be due to an increase in the pore size of channels containing NR1(N616G) or NR2A(N615G), which allows passage of the bulky head group of N1-DnsSpm. In contrast to N1-DnsSpm, N1-OsSpm could easily permeate wild-type NR1/NR2A channels, presumably because the head group of N1-OsSpm can pass through the narrowest part of the channel pore. N-Sulfonyl-polyamines such as N1-DnsSpm and N1-OsSpm represent a new class of polyamine antagonists with which to study glutamate receptor ion channels.
Amino Acid Sequence↗
Block and modulation of N-methyl-D-aspartate receptors by polyamines and protons: role of amino acid residues in the transmembrane and pore-forming regions of NR1 and NR2 subunits.
N-Methyl-D-aspartate (NMDA) receptors are modulated by extracellular spermine and protons and are blocked in a voltage-dependent manner by spermine and polyamine derivatives such as N1-dansyl-spermine (N1-DnsSpm). The effects of mutations in the first and third transmembrane domains (M1 and M3) and the pore-forming loop (M2) of NMDA receptor subunits were studied. Surprisingly, some mutations in M2 and M3 of the NR1 subunit, including mutations at W608 and N616 in M2, reduced spermine stimulation and proton inhibition. These mutations may have long-range allosteric effects or may change spermine- and pH-dependent gating processes rather than directly affecting the binding sites for these modulators because spermine stimulation and proton inhibition are not voltage dependent and are thought to involve binding sites outside the pore-forming regions of the receptor. A number of mutations in M1-M3, including mutations at tryptophan and tyrosine residues near the extracellular sides of M1 and M3, reduced block by spermine and N1-DnsSpm. The effects of these mutants on channel block were characterized in detail by using N1-DnsSpm, which produces block but not stimulation of NMDA receptors. Block by N1-DnsSpm was studied by using voltage ramps analyzed with the Woodhull model of channel block. Mutations at W563 (in M1) and E621 (immediately after M2) in the NR1A subunit and at Y646 (in M3) and N616 (in the M2 loop) in the NR2B subunit reduced the affinity for N1-DnsSpm without affecting the voltage dependence of block. These residues may form part of a binding site for N1-DnsSpm. Mutation of a tryptophan residue at position W607 in the M2 region of NR2B greatly reduced block by N1-DnsSpm, and N1-DnsSpm could easily permeate channels containing this mutation. The results suggest that at least parts of the M1 and M3 segments contribute to the pore or vestibule of the NMDA channel and that a tryptophan in M2 (W607 in NR2B) may contribute to the narrow constriction of the pore.
Amino Acid Sequence↗
Utility of helical computed tomography in the study of arytenoid dislocation and arytenoid subluxation.
Conventional computed tomography (CT) has been considered a mainstay in the evaluation of the larynx. A major difficulty with utilizing this modality, especially in the study of the arytenoid, is the time necessary to perform a thin-slice examination through a structure that has a propensity to move with respiration and swallowing. Helical CT not only significantly reduces the time necessary to study the larynx, but enables one to perform multiple high-resolution multiplanar reconstructions. Eleven patients with arytenoid abnormalities documented by strobovideolaryngoscopy or direct laryngoscopy were imaged with helical CT. A comprehensive radiographic examination illustrating the cricoarytenoid relationship in all of the subjects was completed in less than 20 seconds by using axial reconstructions in 2-mm-thick slices at 1-mm intervals, with subsequently derived sagittal and coronal reconstructions. Helical CT may be a useful adjunct in the diagnosis of arytenoid subluxation or dislocation.
Adult↗
Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night.
To determine whether a cumulative sleep debt (in a range commonly experienced) would result in cumulative changes in measures of waking neurobehavioral alertness, 16 healthy young adults had their sleep restricted 33% below habitual sleep duration, to an average 4.98 hours per night [standard deviation (SD) = 0.57] for seven consecutive nights. Subjects slept in the laboratory, and sleep and waking were monitored by staff and actigraphy. Three times each day (1000, 1600, and 2200 hours) subjects were assessed for subjective sleepiness (SSS) and mood (POMS) and were evaluated on a brief performance battery that included psychomotor vigilance (PVT), probed memory (PRM), and serial-addition testing, Once each day they completed a series of visual analog scales (VAS) and reported sleepiness and somatic and cognitive/emotional problems. Sleep restriction resulted in statistically robust cumulative effects on waking functions. SSS ratings, subscale scores for fatigue, confusion, tension, and total mood disturbance from the POMS and VAS ratings of mental exhaustion and stress were evaluated across days of restricted sleep (p = 0.009 to p = 0.0001). PVT performance parameters, including the frequency and duration of lapses, were also significantly increased by restriction (p = 0.018 to p = 0.0001). Significant time-of-day effects were evident in SSS and PVT data, but time-of-day did not interact with the effects of sleep restriction across days. The temporal profiles of cumulative changes in neurobehavioral measures of alertness as a function of sleep restriction were generally consistent. Subjective changes tended to precede performance changes by 1 day, but overall changes in both classes of measure were greatest during the first 2 days (P1, P2) and last 2 days (P6, P7) of sleep restriction. Data from subsets of subjects also showed: 1) that significant decreases in the MSLT occurred during sleep restriction, 2) that the elevated sleepiness and performance deficits continued beyond day 7 of restriction, and 3) that recovery from these deficits appeared to require two full nights of sleep. The cumulative increase in performance lapses across days of sleep restriction correlated closely with MSLT results (r = -0.95) from an earlier comparable experiment by Carskadon and Dement (1). These findings suggest that cumulative nocturnal sleep debt had a dynamic and escalating analog in cumulative daytime sleepiness and that asymptotic or steady-state sleepiness was not achieved in response to sleep restriction.
Adult↗
Benzyl-polyamines: novel, potent N-methyl-D-aspartate receptor antagonists.
The effects of benzyl-polyamines were studied at recombinant N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus laevis oocytes. A number of mono-, di- and tri-benzyl polyamines, having benzyl substitutions on the terminal or central amino groups, inhibited responses of NR1/NR2 receptors in oocytes voltage-clamped at -70 mV. Among the most potent compounds was N1,N4, N8-tri-benzyl-spermidine (TB-3-4), which had an IC50 value of 0.2 microM. TB-3-4 was approximately 40-fold more potent at NR1/NR2A and NR1/NR2B receptors than at NR1/NR2C or NR1/NR2D receptors. Block by TB-3-4 was strongly voltage dependent. Using voltage ramps analyzed by the Woodhull model of voltage-dependent channel block, TB-3-4 was found to have a Kd(0) value of 5 microM and a zdelta value of 1.41 at NR1/NR2B channels, whereas the affinity of binding [Kd(0) = 250 microM] but not the degree of voltage-dependence (zdelta = 1.43) was much lower at NR1/NR2D channels. At a concentration of 10 microM, TB-3-4 had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors expressed from the GluR1 subunit, indicating that TB-3-4 is a selective NMDA antagonist. TB-3-4 did not permeate wild-type NMDA channels but could easily permeate channels containing an N616G mutation in the NR1 subunit. This mutation is presumed to increase the size of the narrowest constriction of the NMDA channel, thus allowing passage of TB-3-4. Benzyl-polyamines such as TB-3-4 represent a structurally novel class of NMDA receptor channel blockers.
Animals↗