bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic Energy Balance Gene Responses in the Sprague‐Dawley Rat to Supplementation of High‐Energy Diet with Liquid Ensure and Subsequent Transfer to Chow
Authors: Archer Z. A. , Rayner D. V. , Barrett P. , Balik A. , Duncan J. S. , Moar K. M. , Mercer J. G.
Published: September 2005

Energy dense, high fat, high sugar, foods and beverages in our diet are a major contributor to the escalating global obesity problem. Here, we examine the physiological and neuroendocrine effects of feeding rats a solid high‐energy (HE) diet with or without a liquid supplement (Ensure) and the consequence of subsequently transferring animals back to chow (C). Outbred Sprague‐Dawley rats were fed C until 49–56 days of age, and then transferred a HE diet for 3 weeks before allocation to one of two weight‐matched groups. Over the next 10 weeks, one group remained on HE diet, whereas the other had access to the liquid diet, chocolate Ensure (EN), in addition to HE diet (HE + EN). Half the rats from each group were then killed, and the remainder were returned to C for 3 weeks. Supplementation of the HE diet with EN accelerated weight gain and increased daily energy intake, adipose tissue mass, and circulating leptin levels. Transferring animals back to C caused a decrease in bodyweight in the HE + EN group, whereas HE animals were weight stable. Both groups also exhibited voluntary hypophagia, although the magnitude and duration of this response was greater in HE + EN animals. The only effect of Ensure on the hypothalamic genes studied was on tyrosine kinase B expression in the ventromedial hypothalamic nucleus (VMH), which was increased in rats given the supplement. Withdrawal of the obesogenic diets decreased gene expression for cocaine‐and‐amphetamine regulated transcript (CART) and dynorphin (DYN) in the arcuate nucleus (ARC), and DYN and brain‐derived neurotrophic factor (BDNF) in the VMH, whereas neuropeptide Y (NPY) gene expression in the ARC was increased. These changes were independent of previous dietary history. EN supplementation generates distinct physiological responses, yet has a minimal effect on hypothalamic neuropeptide or receptor gene expression, possibly due to the development of leptin resistance. Withdrawal of obesogenic diets induces changes in the gene expression consistent with NPY, CART and BDNF attempting to oppose weight gain on either HE or HE + EN.
Modulated fatty acid desaturation via overexpression of two distinctω‐3 desaturases differentially alters tolerance to various abiotic stresses in transgenic tobacco cells and plants
Authors: Zhang Meng , Barg Rivka , Yin Mingan , Gueta‐Dahan Yardena , Leikin‐Frenkel Alicia , Salts Yehiam , Shabtai Sara , Ben‐Hayyim Gozal
Published: September 2005

Changes in the degree of fatty acid (FA) desaturation are implicated in plant responses to various abiotic stresses, including heat, salt and drought. However, it is still not known whether decreased levels of linolenic acid, found in many plants subjected to salt and drought stress, reflect a mechanism of defence or damage. We addressed this question by generating tobacco cells and plants ectopically overexpressing two FA desaturases: the cytosolicFAD3or the plastidicFAD8. A remarkable increase in the ratio of total linolenic to linoleic acids resulted from overexpression ofFAD3, whereas ectopic overexpression ofFAD8induced an increased ratio mainly in the plastidic lipids. Here we present evidence that overexpressingFAD8imposes much greater heat sensitivity than doesFAD3overexpression, in both cultured cells and whole plants. Overexpression of eitherFAD3orFAD8increases tolerance to drought in tobacco plants and to osmotic stress in cultured cells. These findings suggest that a drought‐induced decreased level of linolenic acid reflects damage. Our results point to the potential of exploitingFADoverexpression as a tool to ameliorate drought tolerance.
Seasonal Variation in Response to Neighbors and Strangers by a Territorial Songbird
Authors: Hyman Jeremy
Published: September 2005

Reduced aggression toward territorial neighbors, termed the ‘dear‐enemy’ effect, is thought to arise because territorial animals benefit by avoiding contests with neighbors with whom they have already established relationships. The dear‐enemy effect has been described in many taxa, but few studies have considered whether or not neighbors’ relationships are affected by changes in the social environment. In this study, I tested whether Carolina wrens,Thryothorus ludovicianus, behaviorally discriminate between neighbors and strangers in two different social environments: in spring when territories have been established for several months, and in fall when an influx of new birds claiming territories might de‐stabilize wren neighborhoods. Comparisons of responses of territorial males to playbacks of songs from neighbors and strangers showed that Carolina wrens show the dear‐enemy effect in spring, but not in fall in this design. The apparent lack of a differential response to neighbors and strangers in fall might be due to a reduction in aggression toward strangers. This study provides evidence that seasonal changes in the dear‐enemy effect coincide with seasonal changes in the social environment.
Testing Problem Solving in Ravens: String‐Pulling to Reach Food
Authors: Heinrich Bernd , Bugnyar Thomas
Published: September 2005

The aim of our study was to re‐examine the acquisition of problem‐solving behaviour in ravens: accessing meat suspended from a perch by a string. In contrast to a previous study, here we: (i) controlled for possible effects of fear of the string, competition by dominants, and social learning and (ii) devised a mechanically equivalent but non‐intuitive task to test for the possibility of means–end understanding. One‐year‐old ravens confronted with meat on a string for the first time tried several ways to reach the food. However, five of six birds suddenly performed a coherent sequence of pulling up and stepping on loops of string, essential for solving the problem. Those five birds were also successful in the non‐intuitive task where they had to pull down the string to lift the meat. A second group of birds with similar exposure to strings but without any experience in pulling up meat failed the pull‐down test. These results support the idea that the ravens’ behaviour in accessing meat on a string is not only a product of rapid learning but may involve some understanding of cause–effect relation between string, food and certain body parts.
Modulation of motor function by stress: a novel concept of the effects of stress and corticosterone on behavior
Authors: Metz Gerlinde A. , Jadavji Nafisa M. , Smith Lori K.
Published: September 2005

Stress and stress hormones affect a variety of behaviors and cognitive abilities. The influences of stress and glucocorticoids on motor function, however, have not been characterized although the presence of glucocorticoid receptors in the motor system has been documented. Here we demonstrate that stress and the stress hormone corticosterone influence motor system function in rats. Groups of adult female Long‐Evans rats underwent either a daily stress‐inducing procedure (immobilization or swimming in cold water) or oral corticosterone treatment. While these treatments continued, animals were tested in skilled reaching and skilled walking tasks for a period of 2 weeks. Both acute (day 1) and chronic (day 14) stress and corticosterone treatment reduced skilled movement accuracy in reaching and walking and increased performance speed. Furthermore, both chronic stress and chronic corticosterone treatment altered skilled movement patterns in the reaching task. These findings indicate that stress modulates motor system function and that these effects are partially mediated by glucocorticoids. To examine whether stress‐induced changes might also derive from enhanced emotionality, rats were treated with the benzodiazepine diazepam. Based on an inverted U‐shaped dose–response relationship, a moderate dose of diazepam significantly improved reaching success while at the same time reducing corticosterone levels. Thus, stress‐associated emotional responses such as anxiety might account for diminished movement accuracy. These results suggest that stress affects the motor system both directly via hormonal changes and indirectly via changes in emotionality. These findings are discussed with respect to the role of stress in motor system function and movement disorders.
Force estimation processing as a function of the input–output relationship of the corticospinal pathway in humans
Authors: Gelli F. , Del Santo F. , Mazzocchio R. , Rossi A.
Published: September 2005

Static changes of the shoulder joint from 30° adduction (ANT) to 30° abduction (POST) in the horizontal plane reduce the gain of the input–output relationship of the corticospinal pathway to the abductor digiti minimi (ADM) muscle [F. Ginanneschi et al. (2005)Exp. Brain Res., 161, 374–382]. The present study examined force estimation under conditions in which the input–output relationship of the corticospinal innervation to ADM was modified by changing shoulder position as above. The input–output relationship was studied using transcranial magnetic stimulation. Estimates of force were assessed using a matching procedure; subjects first matched a target level (10–40% of maximum) on a screen by applying a reference (Ref) isometric contraction of ADM and then they reproduced the same level of force without visual feedback by a test contraction (Test). When Ref and Test contractions were performed at either ANT or POST (i.e. the same input–output), the respective force levels were closely matched. In contrast, when the Test and Ref were performed in POST and ANT, respectively (i.e. different input–output), subjects exerted more force than required. Errors were in the opposite direction when the Test and Ref were in ANT and POST, respectively. The present results suggest that the process of force estimation is based on the effort : tension ratio which is a direct function of the corticomotoneuronal input–output relationship. This notion may contribute to explaining the pathophysiology of central fatigue.
Differential modulation in human primary and secondary somatosensory cortices during the preparatory period of self‐initiated finger movement
Authors: Wasaka Toshiaki , Nakata Hiroki , Akatsuka Kosuke , Kida Tetsuo , Inui Koji , Kakigi Ryusuke
Published: September 2005

To elucidate the mechanisms underlying sensorimotor integration, we investigated modulation in the primary (SI) and secondary (SII) somatosensory cortices during the preparatory period of a self‐initiated finger extension. Electrical stimulation of the right median nerve was applied continuously, while the subjects performed a self‐initiated finger extension and were instructed not to pay attention to the stimulation. The preparatory period was divided into five sub‐periods from the onset of the electromyogram to 3000 ms before movement and the magnetoencephalogram signals following stimulation in each sub‐period were averaged. Multiple source analysis indicated that the equivalent current dipoles (ECDs) were located in SI and bilateral SII. Although the ECD moment for N20m (the upward deflection peaking at around 20 ms) was not significantly changed, that for P30m (the downward deflection peaking at around 30 m) was significantly smaller in the 0‐ to −500‐ms sub‐period than the −2000‐ to −3000‐ms sub‐period. As for SII, the ECD moment for the SII ipsilateral to movement showed no significant change, while that for the contralateral SII was significantly larger in the 0‐ to −500‐ms sub‐period than the −1500‐ to −2000‐ms or −2000‐ to −3000‐ms sub‐period. The opposite effects of movement on SI and SII cortices indicated that these cortical areas play a different role in the function of the sensorimotor integration and are affected differently by the centrifugal process.
Brain‐derived neurotrophic factor induces a rapid dephosphorylation of tau protein through a PI‐3Kinase signalling mechanism
Authors: Elliott Evan , Atlas Roee , Lange Aya , Ginzburg Irith
Published: September 2005

The microtubule‐associated protein tau is essential for microtubule stabilization in neuronal axons. Hyperphosphorylation and intracellular fibrillar formation of tau protein is a pathology found in Alzheimer's disease (AD) brains, and in a variety of neurodegenerative disorders referred to as ‘taupathies’. In the present study, we investigated how brain‐derived neurotrophic factor (BDNF), an extracellular factor that is down‐regulated in AD brains, affects tau phosphorylation. BDNF stimulation of neuronally differentiated P19 mouse embryonic carcinoma cells resulted in a rapid decrease in tau phosphorylation, at phosphorylation sites recognized by Tau1, AT8, AT180 and p262‐Tau antibodies. K252a, a tyrosine receptor kinase (Trk) inhibitor, attenuated this dephosphorylation event, suggesting that BNDF activation of TrkB is responsible for the tau dephosphorylation. In addition, BDNF had no affect on tau phosphorylation in the presence of wortmannin, a PI‐3Kinase inhibitor, or lithium, a GSK3β inhibitor, suggesting that these two kinases are part of the signaling transduction cascade leading from TrkB receptor activation to tau dephosphorylation. These results suggest a link between a correlate of AD, decrease in BDNF levels and an AD pathology, tau hyperphosphorylation.
An fMRI study of causal judgments
Authors: Satpute Ajay B. , Fenker Daniela B. , Waldmann Michael R. , Tabibnia Golnaz , Holyoak Keith J. , Lieberman Matthew D.
Published: September 2005

The capacity to evaluate causal relations is fundamental to human cognition, and yet little is known of its neurocognitive underpinnings. A functional magnetic resonance imaging study was performed to investigate an hypothesized dissociation between the use of semantic knowledge to evaluate specifically causal relations in contrast to general associative relations. Identical pairs of words were judged for causal or associative relations in different blocks of trials. Causal judgments, beyond associative judgments, generated distinct activation in left dorsolateral prefrontal cortex and right precuneus. These findings indicate that the evaluation of causal relations in semantic memory involves additional neural mechanisms relative to those required to evaluate associative relations.
Hyperthermic reactions induced by orexin A: role of the ventromedial hypothalamus
Authors: Monda M. , Viggiano An. , Viggiano Al. , Viggiano E. , Lanza A. , De Luca V.
Published: September 2005

This experiment tested the involvement of the ventromedial hypothalamus (VMH) in the sympathetic and hyperthermic reactions induced by an intracerebroventricular (i.c.v.) injection of orexin A (1.5 nmol). In the first part of the experiment, the firing rate and cytochrome oxidase activity of the VMH neurons, and the colonic temperature were monitored in 12 urethane‐anaesthetized rats before an i.c.v. injection of orexin and over a period of 2 h after the injection. Orexin induced an increase in the firing rate, colonic temperature and cytochrome oxidase activity. A group of 12 rats was used as a control: saline, but not orexin, was injected. No modifications in the firing rate, cytochrome oxidase reactivity and colonic temperature were noted. In the second part of the experiment, 12 rats were anaesthetized and lesioned bilaterally in the VMH with an injection of ibotenic acid. Sham lesions were carried out in 12 control rats. After 48 h, all animals were anaesthetized with ethyl‐urethane. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored before and over a period of 2 h after an i.c.v. injection of orexin or saline in the lesioned and sham‐lesioned rats. Orexin increased the sympathetic firing rate, IBAT and colonic temperatures and heart rate in the sham‐lesioned rats. These increases were reduced by lesion of VMH. Saline did not induce any modification. These findings indicate that the VMH is involved in the control of the orexin‐induced hyperthermia.
Selective rather than inductive mechanisms favour specific replacement of Purkinje cells by embryonic cerebellar cells transplanted to the cerebellum of adult Purkinje cell degeneration (pcd) mutant mice
Authors: Carletti Barbara , Rossi Ferdinando
Published: September 2005

Cell replacement after neuronal degeneration in the adult CNS depends on the availability of specific cues to direct specification, differentiation and integration of newly born neurons into mature circuits. Following recent reports indicating that neurogenic signals may be reactivated in the adult injured CNS, here we asked whether such signals are expressed in the cerebellum after Purkinje cell degeneration. Thus, we compared the fate of embryonic cerebellar cells transplanted to the cerebella of adult wild‐type and Purkinje cell degeneration (pcd) mutant mice. Donor cells were dissected from β‐actin‐enhanced green fluorescent protein (EGFP) transgenic mice and transplanted as a single cell suspension. In both hosts, grafted cells generated all major cerebellar phenotypes, with a precise localization in the recipient cortex or white matter. Nevertheless, the phenotypic distributions showed striking quantitative differences. Most notably, in the pcd cerebellum there was a higher amount of Purkinje cells, while other phenotypes were less frequent. Analysis of cell proliferation by 5‐bromo‐2′‐deoxyuridine (BrDU) incorporation revealed that in both hosts mitotic activity was strongly reduced shortly after transplantation, and virtually all donor Purkinje cells were actually generated before grafting. Together, these results indicate that some compensatory mechanisms operate in the pcd environment. However, the very low mitotic rate of transplanted cells suggests that the adult cerebellum, either wild‐type or mutant, does not provide instructive neurogenic cues to direct the specification of uncommitted progenitors. Rather, specific replacement in mutant hosts is achieved through selective mechanisms that favour the survival and integration of donor Purkinje cells at the expense of other phenotypes.
The role of phenotypic variation in rhizosphere Pseudomonas bacteria
Authors: Van Den Broek Daan , Bloemberg Guido V. , Lugtenberg Ben
Published: September 2005

Colony phase variation is a regulatory mechanism at the DNA level which usually results in high frequency, reversible switches between colonies with a different phenotype. A number of molecular mechanisms underlying phase variation are known: slipped‐strand mispairing, genomic rearrangements, spontaneous mutations and epigenetic mechanisms such as differential methylation. Most examples of phenotypic variation or phase variation have been described in the context of host–pathogen interactions as mechanisms allowing pathogens to evade host immune responses. Recent reports indicate that phase variation is also relevant in competitive root colonization and biological control of phytopathogens. Many rhizospere Pseudomonas species show phenotypic variation, based on spontaneous mutation of the gacA and gacS genes. These morphological variants do not express secondary metabolites and have improved growth characteristics. The latter could contribute to efficient root colonization and success in competition, especially since (as shown for one strain) these variants were observed to revert to their wild‐type form. The observation that these variants are present in rhizosphere‐competent Pseudomonas bacteria suggests the existence of a conserved strategy to increase their success in the rhizosphere.
Novel hydrolase diversity retrieved from a metagenome library of bovine rumen microflora
Authors: Ferrer Manuel , Golyshina Olga V. , Chernikova Tatyana N. , Khachane Amit N. , Reyes‐Duarte Dolores , Santos Vitor A. P. Martins Dos , Strompl Carsten , Elborough Kieran , Jarvis Graeme , Neef Alexander , Yakimov Michail M. , Timmis Kenneth N. , Golyshin Peter N.
Published: September 2005

A metagenome expression library of bulk DNA extracted from the rumen content of a dairy cow was established in a phage lambda vector and activity‐based screening employed to explore the functional diversity of the microbial flora. Twenty‐two clones specifying distinct hydrolytic activities (12 esterases, nine endo‐β‐1,4‐glucanases and one cyclodextrinase) were identified in the library and characterized. Sequence analysis of the retrieved enzymes revealed that eight (36%) were entirely new and formed deep‐branched phylogenetic lineages with no close relatives among known ester‐ and glycosyl‐hydrolases. Bioinformatic analyses of the hydrolase gene sequences, and the sequences and contexts of neighbouring genes, suggested tentative phylogenetic assignments of the rumen organisms producing the retrieved enzymes. The phylogenetic novelty of the hydrolases suggests that some of them may have potential for new applications in biocatalysis.
Detection of glial fibrillary acidic protein (GFAP) and vimentin (Vim) by immunoelectron microscopy of the glial cells in the central nervous system of the snail Megalobulimus abbreviatus
Authors: Dos Santos Paula C. , Gehlen Günther , Faccioni‐Heuser M. Cristina , Achaval Matilde
Published: September 2005

When examined under an electron microscope, the central nervous system of Megalobulimus abbreviatus showed two types of glial cells: firstly, protoplasmic glial cells which displayed a nucleus with peripheral heterochromatin, scanty or no intermediate filaments, a developed Golgi complex, rough and smooth endoplasmic reticula, mitochondria and polymorphic lysosomes that indicate phagocytic activity of debris from the extracellular space; and, secondly, fibrous glial cells which showed numerous glial fibrillary acidic protein (GFAP) and vimentin immunoreactive intermediate filament bundles, a discrete Golgi complex, mitochondria, endoplasmic reticulum, lipid droplets and lysosomes. The contacts between the glial cells consisted of desmosomes and puncta adherentia, while those between the glial cells and the basal lamina consisted of hemidesmosomes. Both glial cell types were located in the cortex and medullary regions, however, the protoplasmic glial cells prevailed in the cortical region, while the fibrous glial cells prevailed in the medullar region. As the nervous tissue is avascular, the passage of nutrients and waste products may be facilitated by the glial labyrinthic system which is located in the cortical region. Glial processes adjacent to large and giant neurones formed a trophospongium, which seemed to be involved in a metabolic exchange between these cells. Thus, this evidence suggests that glial cells of M. abbreviatus are involved in structural support, isolation of different ganglionic areas, the formation of a microcirculatory system and an intimate metabolic relationship with neurones.
Altered expression of neprilysin family members in the pituitary gland of sleep‐disturbed rats, an animal model of severe fatigue
Authors: Ogawa Tokiko , Kiryu‐Seo Sumiko , Tanaka Masaaki , Konishi Hiroyuki , Iwata Nobuhisa , Saido Takaomi , Watanabe Yasuyoshi , Kiyama Hiroshi
Published: September 2005

Alterations of the expression of some peptidases in the pituitary gland of a fatigued rat model were identified. Rats were kept in a cage filled with water to a height of 1.5 cm to disturb deep sleep. After 24‐h sleep disturbance, expression of neutral endopeptidase 24.11 (neprilysin) mRNA was increased in the intermediate lobe of the pituitary gland, whereas the mRNA expression of another family member, damage‐induced neuronal endopeptidase, which is normally expressed in a subgroup of anterior pituitary cells, was significantly suppressed. These alterations were demonstrated by RT‐PCR, northern blotting and in situ hybridization. Other family members, such as neprilysin 2 and endothelin converting enzyme‐1, did not show any change in mRNA expression. An increase of neprilysin mRNA expression was not seen in any other tissues of the sleep‐disturbed rats. The enzymatic activity of neprilysin was also increased in the pituitary. The augmentation of neprilysin expression and activity was prolonged as long as the sleep disturbance continued (up to 5 days), and returned to the basal level when rats were allowed to sleep freely. These results suggest that peptide processing and degradation in the pituitary may be an influential factor in fatigued states such as sleep disturbance.
The blood–brain barrier transmigrating single domain antibody: mechanisms of transport and antigenic epitopes in human brain endothelial cells
Authors: Abulrob Abedelnasser , Sprong Hein , En Henegouwen Paul Van Bergen , Stanimirovic Danica
Published: September 2005

Antibodies against receptors that undergo transcytosis across the blood–brain barrier (BBB) have been used as vectors to target drugs or therapeutic peptides into the brain. We have recently discovered a novel single domain antibody, FC5, which transmigrates across human cerebral endothelial cells in vitro and the BBB in vivo. The purpose of this study was to characterize mechanisms of FC5 endocytosis and transcytosis across the BBB and its putative receptor on human brain endothelial cells. The transport of FC5 across human brain endothelial cells was polarized, charge independent and temperature dependent, suggesting a receptor‐mediated process. FC5 taken up by human brain endothelial cells co‐localized with clathrin but not with caveolin‐1 by immunochemistry and was detected in clathrin‐enriched subcellular fractions by western blot. The transendothelial migration of FC5 was reduced by inhibitors of clathrin‐mediated endocytosis, K+ depletion and chlorpromazine, but was insensitive to caveolae inhibitors, filipin, nystatin or methyl‐β‐cyclodextrin. Following internalization, FC5 was targeted to early endosomes, bypassed late endosomes/lysosomes and remained intact after transcytosis. The transcytosis process was inhibited by agents that affect actin cytoskeleton or intracellular signaling through PI3‐kinase. Pretreatment of human brain endothelial cells with wheatgerm agglutinin, sialic acid, α(2,3)‐neuraminidase or Maackia amurensis agglutinin that recognizes α(2,3)‐, but not with Sambucus nigra agglutinin that recognizes α(2,6) sialylgalactosyl residues, significantly reduced FC5 transcytosis. FC5 failed to recognize brain endothelial cells‐derived lipids, suggesting that it binds luminal α(2,3)‐sialoglycoprotein receptor which triggers clathrin‐mediated endocytosis. This putative receptor may be a new target for developing brain‐targeting drug delivery vectors.
Induction of endogenous pathways by antiepileptics and clinical implications
Authors: Strolin Benedetti M. , Ruty B. , Baltes E.
Published: September 2005

The aim of this study was to review modifications of the endogenous pathways (e.g. enzyme elevations, normal body constituent depletion or higher formation/excretion of endogenous metabolites) which could be ascribed to enzyme induction by antiepileptic drugs (AEDs). Information on older (e.g. phenobarbital, phenytoin and carbamazepine) and newer drugs (where information is available) is discussed together with clinical implications. The enzymes involved in the endogenous pathways and induced by the AEDs will not be limited to the hepatic microsomal enzymes; extrahepatic enzymes and/or enzymes present in other subcellular fractions will also be discussed, if pertinent. The induction of endogenous pathways by AEDs has been taken into account in the past, but much less emphasis has been given compared with the extensive literature on induction by AEDs of the metabolism of concomitantly administered drugs, either of the same or of different classes. Not all of the endogenous pathways examined and induced by AEDs appear to result in serious clinical consequences (e.g. induction of hepatic ALP, increased excretion of d‐glucaric acid or of 6β‐hydroxycortisol). In some cases, induction of some pathways (e.g. increase of high‐density lipoprotein cholesterol or of conjugated bilirubin) might even be a beneficial side‐effect, however enzyme induction is considered rather a detrimental aspect for an AED, as induction is generally a broad and a non‐specific phenomenon. The new AEDs have generally less induction potential than the older agents. Yet some (felbamate, topiramate, oxcarbazepine and lamotrigine) have the potential for inducing enzymes, whereas others (levetiracetam, gabapentin and vigabatrin) appear to be completely devoid of enzyme inducing characteristics, at least as far as the enzymes investigated are concerned.
Topiramate prevents ecstasy consumption: a case report
Authors: Akhondzadeh Shahin , Hampa Ali Daliri
Published: September 2005

The last decade has witnessed a development in the phenomenon ‘ecstasy’. Several substances, with more or less the same effects, are grouped together by the term ecstasy, the best‐known one being 3,4‐methylenedioxymethamphetamine (MDMA). The psychopathological consequences of MDMA in humans are relatively poorly understood. In addition, the treatment approach is complicated by the lack of documented studies. Topiramate is an antiepileptic drug that has a broad spectrum of antiseizure effects, which appear to be the result of several neurostabilizing pharmacological mechanisms including facilitation of GABAergic neurotransmission and inhibition of glutametergic activity at AMPA/kainate receptors. As both GABAergic and glutametergic neurons appear to be important modulators of the brain reward system, it was postulated that topiramate would be an effective treatment for reducing MDMA consumption through the attenuation of MDMA‐induced euphoria. The case of an ecstasy consumer, who started to discontinue ecstasy under topiramate treatment is presented here. Antiepileptics/mood stabilizers with glutamate inhibition activity like topiramate may present a promising new approach for challenging the consequence of drug abuse.
l‐Arginine and melatonin interaction in rat intestinal ischemia–reperfusion
Authors: Arslan S. Oktay , Gelir Ethem , Sayan Hale , Haktan Ozacmak V.
Published: September 2005

We investigated the combinative effects of l‐arginine and melatonin on the contractile responses of terminal ileum after the intestinal ischemia–reperfusion (I/R), in vivo. Male rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (180 min). We have observed a dramatic decrease in spontaneous basal activity and Ach‐induced contractile response. Our data clearly showed that the contractility decrease was ameliorated by l‐arginine but not by l‐NAME. Melatonin has reversed the inhibition of contractility caused by I/R injury in part. We did not observe an augmentation in the contractility of ileum when we use melatonin and l‐arginine in combination, in fact, melatonin decreased the protective effect of l‐arginine in intestinal I/R injury.
Welfare to Work, Wages and Wage Growth*
Authors: Lydon Reamonn , Walker Ian
Published: September 2005

This paper attempts to uncover the effects of a UK welfare‐to‐work programme on individual wage growth by exploiting an expansion to this welfare programme. The conventional wisdom is that such programmes trap recipients into low‐wage, low‐quality work – this comes from the simple argument that the ‘poverty trap’, which a wage subsidy for low‐income workers induces, reduces thebenefitsto investments, such as on‐the‐job training, and so reduces wage growth. In fact, a wage subsidy will also reduce thecostsof, at least, general training because we would normally expect workers to pay for their own general training in the form of lower gross wages. So a wage subsidy is a way of sharing these costs with the taxpayer. Thus, the net effect on wage progression depends on whether it reduces costs by more or less than it reduces the benefits.
Measuring Diagnoses: ICD Code Accuracy
Authors: O'Malley Kimberly J. , Cook Karon F. , Price Matt D. , Wildes Kimberly Raiford , Hurdle John F. , Ashton Carol M.
Published: September 2005

Objective. To examine potential sources of errors at each step of the described inpatient International Classification of Diseases (ICD) coding process.

Data Sources/Study Setting. The use of disease codes from the ICD has expanded from classifying morbidity and mortality information for statistical purposes to diverse sets of applications in research, health care policy, and health care finance. By describing a brief history of ICD coding, detailing the process for assigning codes, identifying where errors can be introduced into the process, and reviewing methods for examining code accuracy, we help code users more systematically evaluate code accuracy for their particular applications.

Study Design/Methods. We summarize the inpatient ICD diagnostic coding process from patient admission to diagnostic code assignment. We examine potential sources of errors at each step and offer code users a tool for systematically evaluating code accuracy.

Principle Findings. Main error sources along the “patient trajectory” include amount and quality of information at admission, communication among patients and providers, the clinician's knowledge and experience with the illness, and the clinician's attention to detail. Main error sources along the “paper trail” include variance in the electronic and written records, coder training and experience, facility quality‐control efforts, and unintentional and intentional coder errors, such as misspecification, unbundling, and upcoding.

Conclusions. By clearly specifying the code assignment process and heightening their awareness of potential error sources, code users can better evaluate the applicability and limitations of codes for their particular situations. ICD codes can then be used in the most appropriate ways.
Dynamic Assessment of Health Outcomes: Time to Let the CAT Out of the Bag?
Authors: Cook Karon F. , O'Malley Kimberly J. , Roddey Toni S.
Published: September 2005

Background.The use of item response theory (IRT) to measure self‐reported outcomes has burgeoned in recent years. Perhaps the most important application of IRT is computer‐adaptive testing (CAT), a measurement approach in which the selection of items is tailored for each respondent.

Objective.To provide an introduction to the use of CAT in the measurement of health outcomes, describe several IRT models that can be used as the basis of CAT, and discuss practical issues associated with the use of adaptive scaling in research settings.

Principal Points.The development of a CAT requires several steps that are not required in the development of a traditional measure including identification of “starting” and “stopping” rules. CAT's most attractive advantage is its efficiency. Greater measurement precision can be achieved with fewer items. Disadvantages of CAT include the high cost and level of technical expertise required to develop a CAT.

Conclusions.Researchers, clinicians, and patients benefit from the availability of psychometrically rigorous measures that are not burdensome. CAT outcome measures hold substantial promise in this regard, but their development is not without challenges.
Proxies and Other External Raters: Methodological Considerations
Authors: Lynn Snow A. , Cook Karon F. , Lin Pay‐Shin , Morgan Robert O. , Magaziner Jay
Published: September 2005

Objective. The purpose of this paper is to introduce researchers to the measurement and subsequent analysis considerations involved when using externally rated data. We will define and describe two categories of externally rated data, recommend methodological approaches for analyzing and interpreting data in these two categories, and explore factors affecting agreement between self‐rated and externally rated reports. We conclude with a discussion of needs for future research.

Data Sources/Study Setting. Data sources for this paper are previous published studies and reviews comparing self‐rated with externally rated data.

Study Design/Data Collection/Extraction Methods. This is a psychometric conceptual paper.

Principal Findings. We define two types of externally rated data: proxy data and other‐rated data. Proxy data refer to those collected from someone who speaks for a patient who cannot, will not, or is unavailable to speak for him or herself, whereas we use the term other‐rater data to refer to situations in which the researcher collects ratings from a person other than the patient to gain multiple perspectives on the assessed construct. These two types of data differ in the way the measurement model is defined, the definition of the gold standard against which the measurements are validated, the analysis strategies appropriately used, and how the analyses are interpreted. There are many factors affecting the discrepancies between self‐ and external ratings, including characteristics of the patient, the proxy, and of the rated construct. Several psychological theories can be helpful in predicting such discrepancies.

Conclusions. Externally rated data have an important place in health services research, but use of such data requires careful consideration of the nature of the data and how it will be analyzed and interpreted.
Measurement Issues in Health Disparities Research
Authors: Ramírez Mildred , Ford Marvella E. , Stewart Anita L. , A. Teresi Jeanne
Published: September 2005

Background.Racial and ethnic disparities in health and health care have been documented; the elimination of such disparities is currently part of a national agenda. In order to meet this national objective, it is necessary that measures identify accurately the true prevalence of the construct of interest across diverse groups. Measurement error might lead to biased results, e.g., estimates of prevalence, magnitude of risks, and differences in mean scores. Addressing measurement issues in the assessment of health status may contribute to a better understanding of health issues in cross‐cultural research.

Objective.To provide a brief overview of issues regarding measurement in diverse populations.

Findings.Approaches used to assess the magnitude and nature of bias in measures when applied to diverse groups include qualitative analyses, classic psychometric studies, as well as more modern psychometric methods. These approaches should be applied sequentially, and/or iteratively during the development of measures.

Conclusions.Investigators performing comparative studies face the challenge of addressing measurement equivalence, crucial for obtaining accurate results in cross‐cultural comparisons.
Impact of Institutional Review Board Practice Variation on Observational Health Services Research
Authors: Green Lee A. , Lowery Julie C. , Kowalski Christine P. , Wyszewianski Leon
Published: September 2005

Objective. To describe, qualitatively and quantitatively, the impact of a review by multiple institutional review boards (IRBs) on the conduct of a multisite observational health services research study.

Data Source and Setting. Primary data collection during 2002, 2003, and 2004 at 43 United States Department of Veterans Affairs (VA) primary care clinics.

Design: Explanatory sequential mixed methods design incorporating qualitative and quantitative elements in sequence.

Data Collection and Abstraction Methods: Field notes and documents collected by research staff during a multisite observational health services research study were used in thematic analysis. Themes were quantified descriptively and merged with timeline data.

Principal Findings: Approximately 4,680 hours of staff time over a 19‐month period were devoted solely to the IRB process. Four categories of phenomena impacting research were observed:

(1) Recruitment, retention, and communication issues with local site principal investigators (PIs). Local PIs had no real role but were required by IRBs. Twenty‐one percent of sites experienced turnover in local PIs, and local PI issues added significant delay to most sites.

(2) Wide variation in standards applied to review and approval of IRB applications. The study was designed to be qualified under U.S. government regulations for expedited review. One site exempted it from review (although it did not qualify for exemption), 10 granted expedited review, 31 required full review, and one rejected it as being too risky to be permitted. Twenty‐three required inapplicable sections in the consent form and five required HIPAA (Health Insurance Portability and Accountability Act of 1996) consent from physicians although no health information was asked of them. Twelve sites requested, and two insisted upon, provisions that directly increased the risk to participants.

(3) Multiple returns for revision of IRB applications, consent documents, and ancillary forms. Seventy‐six percent of sites required at least one resubmission, and 15 percent of sites required three or more (up to six) resubmissions. Only 12 percent of sites required any procedural or substantive revision; most resubmissions were editorial changes to the wording of the consent document.

(4) Process failures (long turnaround times, lost paperwork, difficulty in obtaining necessary forms, unavailability of key personnel at IRBs). The process required from 52 to 798 (median 286) days to obtain approval at each site.

Conclusions. Several features of the IRB system as currently configured impose costly burdens of administrative activity and delay on observational health services research studies, and paradoxically decrease protection of human subjects. Central review with local opt‐out, cooperative review, or a system of peer review could reduce costs and improve protection of human subjects.
The Effects of Child‐Only Insurance Coverage and Family Coverage on Health Care Access and Use: Recent Findings among Low‐Income Children in California
Authors: Guendelman Sylvia , Wier Megan , Angulo Veronica , Oman Doug
Published: September 2005

Objective. To compare the extent with which child‐only and family coverage (child and parent insured) ensure health care access and use for low income children in California and discuss the policy implications of extending the State Children's Health Insurance Program (California's Healthy Families) to uninsured parents of child enrollees.

Data Sources/Setting. We used secondary data from the 2001 California Health Interview Survey (CHIS), a representative telephone survey.

Study Design. We conducted a cross‐sectional study of 5,521 public health insurance–eligible children and adolescents and their parents to examine the effects of insurance (family coverage, child‐only coverage, and no coverage) on measures of health care access and utilization including emergency room visits and hospitalizations.

Data Collection. We linked the CHIS adult, child, and adolescent datasets, including the adolescent insurance supplement.

Findings. Among the sampled children, 13 percent were uninsured as were 22 percent of their parents. Children without insurance coverage were more likely than children with child‐only coverage to lack a usual source of care and to have decreased use of health care. Children with child‐only coverage fared worse than those with family coverage on almost every access indicator, but service utilization was comparable.

Conclusions. While extending public benefits to parents of children eligible for Healthy Families may not improve child health care utilization beyond the gains that would be obtained by exclusively insuring the children, family coverage would likely improve access to a regular source of care and private sector providers, and reduce perceived discrimination and breaks in coverage. These advantages should be considered by states that are weighing the benefits of expanding health insurance to parents.
Psychometric Properties of the Dutch Version of the Hospital‐Level Consumer Assessment of Health Plans Survey®Instrument
Authors: Arah Onyebuchi A. , Ten Asbroek A. H. A. , Delnoij Diana M. J. , De Koning Johan S. , Stam Piet J. A. , Poll Aldien H. , Vriens Barbara , Schmidt Paul F. , Klazinga Niek S.
Published: September 2005

Objectives.To assess the reliability and validity of a translated version of the American Hospital‐level Consumer Assessment of Health Plans Survey® (H‐CAHPS) instrument for use in Dutch health care.

Data Sources/Study Setting.Primary survey data from adults aged 18 years or more who were recently discharged from two multispecialty city hospitals in the Netherlands.

Study Design.We used forward and backward translation procedures and a panel of experts to adapt the 66‐item pilot H‐CAHPS into a 70‐item Dutch instrument. Descriptive statistics and standard psychometric methods were then used to test the reliability and validity of the new instrument.

Data Collection.From late November 2003 to early January 2004, the survey was administered by mail to 1,996 patients discharged within the previous 2 months.

Principal Findings.Analyses supported the reliability and validity of the following 7‐factor H‐CAHPS structure for use in Dutch hospitals: on doctor's communication, nurses' communication, discharge information, communication about medication, pain control, physical environment of hospital, and nursing services. The internal consistency reliability of the scales ranged from 0.60 to 0.88. Items related to “family receiving help when on visit,”“hospital staff introducing self,” and “admission delays” did not improve the psychometric properties of the new instrument.

Conclusions.These findings suggest that the H‐CAHPS instrument is reliable and valid for use in the Dutch context. However, more research will be needed to support its equivalence to the United States version, and its use for between‐hospital comparisons.
Seroprevalence and Risk Factors for Helicobacter pylori Infection in Greenlanders
Authors: Koch Anders , Krause Tyra Grove , Krogfelt Karen , Olsen Ove Rosing , Fischer Thea Kølsen , Melbye Mads
Published: September 2005

Background.  In contrast to most populations worldwide, the incidence of gastric cancer increases among Inuit in Greenland. Contributing factors to this increase are unknown, but Helicobacter pylori may be involved. However, little is known regarding the epidemiology of H. pylori in Arctic communities. With the aim of determining age‐specific prevalence, risk factors, and association with clinical conditions of H. pylori infection, we carried out a population‐based study of H. pylori in Sisimiut, the second biggest town of Greenland.

Materials and Methods.  A population‐based sample of 685 persons had serum drawn that was analyzed for H. pylori IgG antibodies using enzyme‐linked immunosorbent assay (ELISA). Risk factors analyses were carried out using multivariate logistic regression models.

Results.  The seroprevalence was lowest among children aged 0–4 years (6%), but increased rapidly thereafter. In persons aged 15–87 years the seroprevalence had stabilized around 58%. Total number of children in household, number of older, but not younger, siblings and narrow age gap to closest older sibling were associated with H. pylori seropositivity. In contrast, number of adults in household and socioeconomic status did not influence serostatus.

Conclusions.  The age‐specific prevalence pattern in Greenland is intermediate between that of developing and developed countries. The risk factor pattern indicates crowding and older siblings in particular to be key elements in risk of infection.
Corporate Yield Spreads: Default Risk or Liquidity? New Evidence from the Credit Default Swap Market
Authors: LONGSTAFF FRANCIS A. , MITHAL SANJAY , NEIS ERIC
Published: September 2005

We use the information in credit default swaps to obtain direct measures of the size of the default and nondefault components in corporate spreads. We find that the majority of the corporate spread is due to default risk. This result holds for all rating categories and is robust to the definition of the riskless curve. We also find that the nondefault component is time varying and strongly related to measures of bond‐specific illiquidity as well as to macroeconomic measures of bond market liquidity.