bluuebunny/crossref_metadata_2025 huggingface dataset:
mRNA with a <20-nt poly(A) tail imparted by the poly(A)-limiting element is translated as efficiently in vivo as long poly(A) mRNA
Authors: PENG JING , SCHOENBERG DANIEL R.
Published: June 2005

The poly(A)-limiting element (PLE) is a conserved sequence that restricts the length of the poly(A) tail to <20 nt. This study compared the translation of PLE-containing short poly(A) mRNA expressed in cells with translation in vitro of mRNAs with varying length poly(A) tails. In transfected cells, PLE-containing mRNA had a <20-nt poly(A) and accumulated to a level 20% higher than a matching control without a PLE. It was translated as well as the matching control mRNA with long poly(A) and showed equivalent binding to polysomes. Translation in a HeLa cell cytoplasmic extract was used to examine the impact of the PLE in the context of varying length poly(A) tails. Here the overall translation of +PLE mRNA was less than control mRNA with the same length poly(A), and the PLE did not overcome the effect of a short poly(A) tail. Because poly(A)-binding protein (PABP) is a dominant effector of poly(A)-dependent translation we reasoned excess PABP in our extract might overwhelm PLE regulation of translation. This was confirmed by experiments where PABP was inactivated with poly(rA) or Paip2, and the effect of both treatments was reversed by addition of recombinant PABP. These data indicate that the PLE functionally substitutes for bound PABP to stimulate translation of short poly(A) mRNA.
RNA chaperone activity of protein components of human Ro RNPs
Authors: BELISOVA AURÉLIA , SEMRAD KATHARINA , MAYER OLIVER , KOCIAN GRAZIA , WAIGMANN ELISABETH , SCHROEDER RENÉE , STEINER GÜNTER
Published: June 2005

Ro ribonucleoprotein (RNP) complexes are composed of one molecule of a small noncoding cytoplasmic RNA, termed Y RNA, and the two proteins Ro60 and La. Additional proteins such as hnRNP I, hnRNP K, or nucleolin have recently been shown to be associated with subpopulations of Y RNAs. Ro RNPs appear to be localized in the cytoplasm of all higher eukaryotic cells but their functions have remained elusive. To shed light on possible functions of Ro RNPs, we tested protein components of these complexes for RNA chaperone properties employing two in vitro chaperone assays and additionally an in vivo chaperone assay. In these assays the splicing activity of a group I intron is measured. La showed pronounced RNA chaperone activity in thecis-splicing assay in vitro and also in vivo, whereas no activity was seen in thetrans-splicing assay in vitro. Both hnRNP I and hnRNP K exhibited strong chaperone activity in the two in vitro assays, however, proved to be cytotoxic in the in vivo assay. No chaperone activity was observed for Ro60 in vitro and a moderate activity was detected in vivo. In vitro chaperone activities of La and hnRNP I were completely inhibited upon binding of Y RNA. Taken together, these data suggest that the Ro RNP components La, hnRNP K, and hnRNP I possess RNA chaperone activity, while Ro60-Y RNA complexes might function as transporters, bringing other Y RNA binding proteins to their specific targets.
Large Deviations with Diminishing Rates
Authors: Shwartz Adam , Weiss Alan
Published: May 2005

The theory of large deviations for jump Markov processes has been generally proved only when jump rates are bounded below, away from zero (Dupuis and Ellis, 1995, The large deviations principle for a general class of queueing systems I. Trans. Amer. Math. Soc. 347 2689–2751; Ignatiouk-Robert, 2002, Sample path large deviations and convergence parameters. Ann. Appl. Probab. 11 1292–1329; Shwartz and Weiss, 1995, Large Deviations for Performance Analysis, Chapman-Hall). Yet, various applications of interest do not satisfy this condition. We describe several classes of models where jump rates diminish to zero in a Lipschitz continuous way. Under appropriate conditions, we prove that the sample path large deviations principle continues to hold. Under our conditions, the rate function remains an integral over a local rate function, which retains its standard representation.
Partially Ball Weakly Inf-Compact Saddle Functions
Authors: Thibault Lionel , Zlateva Nadia
Published: May 2005

We study on a product Banach space the properties of a class of saddle functions called partially ball weakly inf-compact. For such a function we prove that the domain of the subdifferential is nonempty, that the operator naturally associated with the subdifferential is maximal monotone, and that the subdifferential of the function is integrable. For a function in a large subclass of that class we prove the density of the domain of the subdifferential in the domain of the function.
Investment Timing Under Incomplete Information
Authors: Décamps Jean-Paul , Mariotti Thomas , Villeneuve Stéphane
Published: May 2005

We study the decision of when to invest in a project whose value is perfectly observable but driven by a parameter that is unknown to the decision maker ex ante. This problem is equivalent to an optimal stopping problem for a bivariate Markov process. Using filtering and martingale techniques, we show that the optimal investment region is characterized by a continuous and nondecreasing boundary in the value-belief state space. This generates path-dependency in the optimal investment strategy. We further show that the decision maker always benefits from an uncertain drift relative to an average drift situation and that the value of the option to invest is not globally increasing with respect to the volatility of the value process.
A Sequential Entry Problem with Forced Exits
Authors: Wang Hui
Published: May 2005

We consider a continuous time optimal stopping problem with multiple entries and forced exits. The value for such an optimization problem with a general payoff function is solved in closed form under the assumption that the state process is a geometric Brownian motion and the forced exits come in according to a Poisson process. The effect due to the forced exits is analyzed. It is shown that the presence of the forced exits is a true risk (meaning that it will reduce the value and enlarge the “continuation” region) if and only if the entry cost is large enough compared to the running cost.
Ultramodular Functions
Authors: Marinacci Massimo , Montrucchio Luigi
Published: May 2005

We study the properties of ultramodular functions, a class of functions that generalizes scalar convexity and that naturally arises in some economic and statistical applications.
Medication Associated with Weight Gain May Influence Outcome in a Weight Management Program
Authors: Malone Margaret , Alger-Mayer Sharon A , Anderson Drew A
Published: June 2005

BACKGROUND

Weight gain is a commonly overlooked adverse effect of some medications that potentially confounds weight loss efforts in individuals who are overweight and obese.

OBJECTIVE

To determine the frequency of use of drugs associated with weight gain by participants and the effect on outcome in a weight management program.

METHODS

Adult patients >18 years of age were recruited from an outpatient, university-based setting to participate in a 20-week structured weight management program.

RESULTS

Ninety patients (74 women) were recruited (mean [± SD] age 48 ± 10 y, mean body mass index 37 ± 6 kg/m 2 ). Patients had multiple diseases including type 2 diabetes mellitus (n = 23), hypertension (n = 48), depression (n = 18), and dyslipidemia (n = 9). The median number of drugs per patient was 4.0 (range 0–15). The median number of drugs associated with weight gain was zero (range 0–3). Forty-three (48%) patients were taking at least one of these agents, including β-blockers (n = 18), selective serotonin-reuptake inhibitors (n = 18), sulfonylureas (n = 7), insulin (n = 9), and thiazolidinediones (n = 6). Seven patients completed ≤6 weeks of the program and were excluded from further analysis, and 83 patients completed 10 weeks. Of these 83 patients, 39 had lost ≤2% of their initial weight; 23 (59%) of those 39 were taking drugs associated with weight gain. Fifty-nine patients completed the full 20 weeks. The mean overall weight loss of completers was 4.8 ± 5.0% (range −5.9 [gain] to 17.1% [loss]) at 20 weeks.

CONCLUSIONS

Patients taking WGDs weighed more at baseline and were less likely to lose weight in this program. Attention should be given when prescribing such medications to obese patients, as this may negatively influence their weight management.
Acute Coffee Ingestion Does Not Affect LDL Cholesterol Level
Authors: Cheung Rebecca J , Gupta Eric K , Ito Matthew K
Published: June 2005

BACKGROUND

Although patients are instructed to abstain from food before having blood drawn for lipid analysis, many still drink coffee in the morning. It is unknown whether coffee consumed prior to drawing blood samples will impact fasting serum lipids.

OBJECTIVE

To determine whether a single 6-oz cup of coffee with or without the addition of nondairy creamer and sugar will significantly affect fasting plasma lipid profiles.

METHODS

This was a prospective, open-label, randomized crossover study. At the first of 2 visits, blood was drawn to measure initial fasting lipid panels, and participants were randomized to drink 6 oz of black coffee or coffee with nondairy creamer and sugar. Within 30–60 minutes of coffee consumption, blood was drawn for follow-up lipid panels. The procedure was repeated at the second visit, except the participants were crossed over to receive the alternate coffee preparation.

RESULTS

Forty participants (26 men; age [mean ± SD] 45 ± 15 y) were enrolled. Total cholesterol (TC) increased from 188.2 ± 38.1 to 191.3 ± 39.9 mg/dL (p = 0.019) and high-density lipoprotein cholesterol (HDL-C) increased from 43.2 ± 12.3 to 44.8 ± 12.9 mg/dL (p < 0.001) after consumption of black coffee. Triglycerides decreased from 145.6 ± 123.7 to 136.3 ± 107.1 mg/dL (p = 0.014) after consumption of coffee with nondairy creamer and sugar. Changes in other lipid parameters, such as low-density lipoprotein cholesterol in either group, were not statistically significant.

CONCLUSIONS

A single cup of coffee consumed within one hour before drawing blood resulted in statistically, but not clinically, significant differences in TC and HDL-C (black coffee) and triglycerides (coffee with creamer and sugar).
Testing alleged mediumship: Methods and results
Authors: O'Keeffe Ciarán , Wiseman Richard
Published: May 2005

Mediums claim to be able to communicate with the deceased. Such claims attract a considerable amount of public interest and, if valid, have important implications for many areas of psychology. For over 100 years, researchers have tested alleged mediums. This work has obtained mixed results and provoked a considerable amount of methodological debate. This paper reviews the key issues in this debate, describes how the authors devised a method of testing that aimed to prevent the many problems that have hindered past research, and how they then used this method to test several professional mediums. The results of this work did not support the existence of genuine mediumistic ability. Competing interpretations of these results are discussed, along with ways in which the methodology presented in the paper could be used to assess conceptually similar, but non‐paranormal, claims made in clinical, occupational and forensic contexts.
Relationships between risk‐taking behaviour and subsequent risk perceptions
Authors: Brown Stephen L.
Published: May 2005

Research has suggested that engagement in patterns of risk‐taking behaviour might have a negative influence on the processing of risk information. However, risk‐takers display higher risk perceptions than non‐risk takers. This paradox might be resolved by removing the confounding effect of risk takers' increased exposure to risk. A longitudinal survey was administered to 255 motorists to examine the extent to which Time 1 (T1) self‐reported speeding behaviour predicted exposure‐free measures of Time 2 (T2) risk perceptions. Hierarchical regression analyses, controlling for demographics and T1 risk perceptions, showed that T1 speeding, and T1 to T2 speeding changes, both inversely predicted T2 risk perceptions. This suggests that successive increments in risk‐taking behaviour will lead to progressively lower increases in personal risk perception. Possible foundations and implications of this effect are discussed.
Source‐monitoring accuracy across repeated tests following directed forgetting
Authors: Goernert Phillip N.
Published: May 2005

The repeated recall of items from lists that participants were earlier instructed to either remember or to forget was examined in two experiments. RR participants (those instructed to remember both lists they were presented) tended to recall more List 1 items than FR participants (those instructed to forget the first list and to remember the second list). FR participants recalled more List 2 items than did RR participants, but only when directed to report those items (Experiment 1), not when directed to report items from both lists (Experiment 2). Participants experienced difficulty correctly reporting the list source of items they recalled and incorrect source recall increased across tests, showing hypermnesia. This later result underscores the need for caution when assessing the accuracy of information retrieved from multiple sources across repeated tests. Together, the data patterns provide support for the retrieval dynamics account of hypermnesia, the context‐change account of directed forgetting, and limited support for the retrieval inhibition view of directed forgetting.
Emergency contraception use and non‐use in young women: The application of a contextual and dynamic model
Authors: Free Caroline , Ogden Jane
Published: May 2005

There have been many approaches to understanding contraception use including social cognition models which have been criticised for their individualistic approach and their static nature. The present quantitative study developed and refined a contextual and dynamic model of contraception use that was derived using qualitative research. This model conceptualizes the predictors of contraception use in terms of the meaning and importance of a range of social goals, perceptions of vulnerability, and constraints on or facilitators of contraception use each of which changes over time. The present study operationalized this model in relation to emergency contraception and explored differences between users and non‐users and between episodes of use and non‐use. In terms of users and non‐users, the results showed that the users of emergency contraception showed a more positive view of an emergency contraception user, perceived greater support from their partner for emergency contraception use, rated themselves more at risk of pregnancy, and felt more confident about asking for emergency contraception. In terms of use and non‐use, use was related to an increased belief about the risk of pregnancy, increased partner support, increased concern about health care professionals and the side‐effects of the drug, and a more positive identity of an emergency contraception. The study has helped to develop and refine the model and has identified some key factors that are specifically relevant to emergency contraception use in a sample of women in education in and around London.
Nobody likes damaged goods: The experience of adult visible acne
Authors: Murray Craig D. , Rhodes Katharine
Published: May 2005

Objectives. While mild to severe acne is a common problem in the teenage years, many adults also suffer from the condition. Although there is an appreciable body of dermatological literature on this issue, the psychosocial concomitants of severe, visible adult acne are little elaborated. The aim of this research is to detail the salient experiences of adults with severe visible acne, and to set out the implications of these experiences.

Design. A phenomenological qualitative approach was adopted to elicit detailed accounts of the impact of visible acne upon the lives of a small sample of sufferers.

Method. 11 adults suffering from severe visible acne took part in semi‐structured interviews via e‐mail, over an extended period of time. Transcripts of these interviews served as the data for an interpretative phenomenological analysis.

Results. Five themes emerged, detailing different aspects of respondents' personal and social lives in the context of their acne. These were: powerlessness and the variable nature of acne; comparisons, self‐image and identity; the experience of general social interaction; relationships with family and friends; and gender, sexuality, and romantic relationships.

Conclusions. These themes allowed a deeper understanding of issues reported in previous quantitative research in the area, as well as revealing findings that had not been previously reported in relation to the experience of adult acne and its impact upon personal and social relationships. With an acknowledgement of these experiences, personal and professional acquaintances have the potential to improve their interpersonal relationship with the person concerned, and encourage positive changes in their psychological health and social interaction.
Discontinuity patterns in stages of the precaution adoption process model: Meat consumption during a livestock epidemic
Authors: Sniehotta Falko F. , Luszczynska Aleksandra , Scholz Urte , Lippke Sonia
Published: May 2005

Objectives. Patterns of changes in social‐cognitive variables were investigated in order to test selected stages of the precaution adoption process model (PAPM). It was hypothesized that non‐linear trends (discontinuity patterns) in perceived vulnerability, positive and negative outcome expectancies, procrastination, and self‐efficacy might be observed across the stages.

Design. Cross‐sectional data from 808 respondents were employed.

Method. Questionnaire data were collected in an on‐line study on meat consumption during a livestock epidemic in Germany. Polynomial trends and analyses of variance with post‐hoc ‐contrasts were used to examine the patterns of change.

Results. Discontinuity patterns were found for perceived vulnerability, negative outcome expectancies, and procrastination. The data provided partial support for discontinuity patterns in self‐efficacy. Continuity patterns were found for positive outcome expectancies.

Conclusions. Results provide support for a stage model rather than a pseudo‐stage model.
Stress, oral health behaviour and clinical outcome
Authors: Deinzer Renate , Granrath Nicole , Spahl Manuela , Linz Sandra , Waschul Bernd , Herforth Armin
Published: May 2005

Objective. Several studies indicate that stress adversely affects various health behaviours. Oral hygiene behaviour, however, has been rarely studied in this context. The present study thus aims to assess the effects of stress on oral hygiene behaviour and clinical outcome.

Design. In a prospective matched controlled design 12 pairs of medical students, each consisting of 1 student participating in a major academic exam and 1 student not participating in any exams (control) were studied.

Methods. A professional tooth cleaning was performed 4 weeks prior to exams to obtain plaque levels of 0 at all sites. Immediately prior to professional tooth cleaning and 4 weeks after exams plaque levels (as indicator of oral hygiene behaviour) and bleeding on probing (an indicator of gingivitis) were assessed.

Results. No group differences were observed at the beginning of the exam period; after exams significant higher rates of plaque (p =.0005, d =1.74) and gingivitis (p =.016, d =1.01) were observed in exam students as compared with controls.

Conclusions. The study illustrates the clinical significance of stress effects on health behaviour. Stress should be included as a factor in models of patient compliance and health behaviour.
The role of pre‐operative state‐anxiety in the determination of intra‐operative neuroendocrine responses and recovery
Authors: Pearson Sue , Maddern Guy J. , Fitridge Robert
Published: May 2005

Objectives. The psychophysiological model of adjustment to surgery predicts associations between (1) heightened pre‐operative state‐anxiety and intra‐operative neuroendocrine responses, (2) neuroendocrine responses and complications; and (3) heightened pre‐operative state‐anxiety and post‐operative recovery. The present study examined these associations.

Methods. Participants were 39 patients (mean age 71.9±6.1 years) undergoing elective carotid endarterectomy surgery under local anaesthesia. In the week prior to surgery, patients completed baseline measures of physical and mental functioning using the MOS 36‐item Short‐Form Health Survey (SF‐36). In addition to this, they undertook a 24‐hour urine save to measure cortisol and catecholamines. Measures of state‐anxiety were completed on the evening prior to surgery. A second 24‐hour urine save was started at the time of anaesthetic induction. Follow‐up measures of physical and mental functioning were completed 1 month following surgery. All complications were recorded during hospitalization.

Results. There was a significant negative association between pre‐operative state‐anxiety and intra‐operative cortisol (r =−.52, p ≤.001). Using hierarchical regression analysis, pre‐operative state‐anxiety accounted for 10% of the variance in intra‐operative cortisol responses after controlling for medical and demographic factors. There were no significant associations between neuroendocrine responses and complications. Pre‐operative state‐anxiety was a significant determinant of poorer mental functioning following surgery, explaining 10% of the variance in scores after adjusting for baseline mental functioning.

Conclusions. Results from this study show increasing pre‐operative anxiety to be associated with lower intra‐operative cortisol responses and poorer mental functioning 1 month following surgery.
Can safer‐sex promotion leaflets change cognitive antecedents of condom use? An experimental evaluation
Authors: Krahé Barbara , Abraham Charles , Scheinberger‐Olwig Renate
Published: May 2005

An experimental evaluation of a safer sex promotion leaflet was undertaken to assess its capacity to change antecedent cognitions of condom use. The leaflet was identified in a previous study as addressing research‐based cognitive antecedents of condom use. A pre‐post‐test experimental study including three conditions was conducted: (a) presentation of the leaflet; (b) presentation of the leaflet plus incentive for systematic processing; (c) no‐leaflet control. The leaflet was evaluated in terms of its capacity to change eight cognitive correlates of condom use identified in a recent meta‐analysis. The sample consisted of 230 tenth‐grade students. Following baseline assessments, leaflet‐induced change was measured immediately following the intervention and at a follow up 4 weeks post‐intervention. The target leaflet alone did not result in significant changes in the cognitive antecedents of condom use compared with the control condition. However, in combination with an incentive for systematic processing, the target leaflet had a greater impact on cognitive antecedents than the no‐leaflet control condition. The findings are discussed with regard to the development and evaluation of research‐based health‐promotion materials.
Shared Brain Areas But Not Functional Connections Controlling Movement Timing and Order
Authors: Garraux Gaëtan , McKinney Christopher , Wu Tao , Kansaku Kenji , Nolte Guido , Hallett Mark
Published: June 2005

Virtually every aspect of the enormous repertoire of human behaviors is embedded in a sequential context, but brain mechanisms underlying the adjustment of two fundamental dimensions defining a motor sequence (order of a series of movements and intervals separating them) as a function of a given goal are poorly understood. Using functional magnetic resonance imaging, we demonstrate that, at the neuronal level, these tasks can only be distinguished by differences in functional interactions between associative areas of common activation, which included bilateral subcortico-parieto-frontal regions, and two subcortical structures. Activity in these shared associative areas was preferentially coupled with that in right putamen during manipulation of timing and with that in right posterior cerebellum during manipulation of serial order. This finding is important because it provides evidence for an efficient organization of the brain during cognitive control of motor sequences and supports a recently proposed principle according to which the role of brain regions involved in different behavioral tasks without differential alterations in their measured activity depends on changes in their interactions with other connected areas as a function of the tasks.
Depolarizing GABA Acts on Intrinsically Bursting Pyramidal Neurons to Drive Giant Depolarizing Potentials in the Immature Hippocampus
Authors: Sipilä Sampsa T. , Huttu Kristiina , Soltesz Ivan , Voipio Juha , Kaila Kai
Published: June 2005

Spontaneous periodic network events are a characteristic feature of developing neuronal networks, and they are thought to play a crucial role in the maturation of neuronal circuits. In the immature hippocampus, these types of events are seen in intracellular recordings as giant depolarizing potentials (GDPs) during the stage of neuronal development when GABAA-mediated transmission is depolarizing. However, the precise mechanism how GABAergic transmission promotes GDP occurrence is not known. Using whole-cell, cell-attached, perforated-patch, and field-potential recordings in hippocampal slices, we demonstrate here that CA3 pyramidal neurons in the newborn rat generate intrinsic bursts when depolarized. Furthermore, the characteristic rhythmicity of GDP generation is not based on a temporally patterned output of the GABAergic interneuronal network. However, GABAergic depolarization plays a key role in promoting voltage-dependent, intrinsic pyramidal bursting activity. The present data indicate that glutamatergic CA3 neurons have an instructive, pacemaker role in the generation of GDPs, whereas both synaptic and tonic depolarizing GABAergic mechanisms exert a temporally nonpatterned, facilitatory action in the generation of these network events.
Relearning Sound Localization with a New Ear
Authors: Van Wanrooij Marc M. , Van Opstal A. John
Published: June 2005

Human sound localization results primarily from the processing of binaural differences in sound level and arrival time for locations in the horizontal plane (azimuth) and of spectral shape cues generated by the head and pinnae for positions in the vertical plane (elevation). The latter mechanism incorporates two processing stages: a spectral-to-spatial mapping stage and a binaural weighting stage that determines the contribution of each ear to perceived elevation as function of sound azimuth. We demonstrated recently that binaural pinna molds virtually abolish the ability to localize sound-source elevation, but, after several weeks, subjects regained normal localization performance. It is not clear which processing stage underlies this remarkable plasticity, because the auditory system could have learned the new spectral cues separately for each ear (spatial-mapping adaptation) or for one ear only, while extending its contribution into the contralateral hemifield (binaural-weighting adaptation). To dissociate these possibilities, we applied a long-term monaural spectral perturbation in 13 subjects. Our results show that, in eight experiments, listeners learned to localize accurately with new spectral cues that differed substantially from those provided by their own ears. Interestingly, five subjects, whose spectral cues were not sufficiently perturbed, never yielded stable localization performance. Our findings indicate that the analysis of spectral cues may involve a correlation process between the sensory input and a stored spectral representation of the subject's ears and that learning acts predominantly at a spectral-to-spatial mapping level rather than at the level of binaural weighting.
Shifts of Effective Connectivity within a Language Network during Rhyming and Spelling
Authors: Bitan Tali , Booth James R. , Choy Janet , Burman Douglas D. , Gitelman Darren R. , Mesulam M.-Marsel
Published: June 2005

We used functional magnetic resonance imaging to examine task-specific modulations of effective connectivity within a left-hemisphere language network during spelling and rhyming judgments on visually presented words. We identified sites showing task-specific activations for rhyming in the lateral temporal cortex (LTC) and for spelling in the intraparietal sulcus (IPS). The inferior frontal gyrus (IFG) and fusiform gyrus were engaged by both tasks. Dynamic causal modeling showed that each task preferentially strengthened modulatory influences converging on its task-specific site (LTC for rhyming, IPS for spelling). These remarkably selective and symmetrical findings demonstrate that the nature of the behavioral task dynamically shifts the locus of integration (or convergence) to the network component specialized for that task. Furthermore, they suggest that the role of the task-selective areas is to provide a differential synthesis of incoming information rather than providing differential control signals influencing the activity of other network components. Our findings also showed that switching tasks led to changes in the target area influenced by the IFG, suggesting that the IFG may play a pivotal role in setting the cognitive context for each task. We propose that task-dependent shifts in effective connectivity are likely to be mediated through top-down modulations from the IFG to the task-selective regions in a way that differentially enhances their sensitivity to incoming word-form information.
Cocaine Experience Establishes Control of Midbrain Glutamate and Dopamine by Corticotropin-Releasing Factor: A Role in Stress-Induced Relapse to Drug Seeking
Authors: Wang Bin , Shaham Yavin , Zitzman Dawnya , Azari Soraya , Wise Roy A. , You Zhi-Bing
Published: June 2005

Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropin-releasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders.
Odorant-Induced Activation of Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase in the Olfactory Bulb Promotes Survival of Newly Formed Granule Cells
Authors: Miwa Naofumi , Storm Daniel R.
Published: June 2005

Extracellular signal-regulated kinase 1/2 (Erk1/2)/mitogen-activated protein (MAP) kinase (MAPK) plays a significant role in neuronal survival, including odorant-induced, activity-dependent survival of olfactory sensory neurons in the main olfactory epithelium. Here, we examined the role of MAPK for the survival of neurons in the olfactory bulb. To study odorant-induced activation of MAPK in the olfactory bulb, mice were exposed to odorantsin vivo, and MAPK was assayed. Exposure of mice to some odorantsin vivoactivated MAPK in granule cells 10 min after exposure. Activation of MAPK was particularly evident in the nucleus and dendrites of granule cells. Because MAPK activation can augment neuronal survival, odorant enhancement of granule cell survival was monitored by bromodeoxyuridine (BrdU) incorporation. Long-term exposure to odorants increased the survival of newly formed granule cells as well as the number of granule cells that were both BrdU+ and phospho-Erk+. Inhibition of MAPK by administration of SL327 invivoblocked the odorant-induced increase in newly formed granule cells, suggesting that activation of MAPK promotes the survival of granule cells in the olfactory bulb. Studies using cultured granule cells confirmed that activation of MAPK in granule cells protects them against strong apoptotic signals. These data suggest that stimulation of MAPK in olfactory bulb granule cells by some odorants may contribute to the survival of newly formed granule cells caused by odorant exposure.
The Primordial, Blue-Cone Color System of the Mouse Retina
Authors: Haverkamp Silke , Wässle Heinz , Duebel Jens , Kuner Thomas , Augustine George J. , Feng Guoping , Euler Thomas
Published: June 2005

Humans and old world primates have trichromatic color vision based on three spectral types of cone [long-wavelength (L-), middle-wavelength (M-), and short-wavelength (S-) cones]. All other placental mammals are dichromats, and their color vision depends on the comparison of L- and S-cone signals; however, their cone-selective retinal circuitry is still unknown. Here, we identified the S-cone-selective (blue cone) bipolar cells of the mouse retina. They were labeled in a transgenic mouse expressing Clomeleon, a chloride-sensitive fluorescent protein, under the control of thethy1promoter. Blue-cone bipolar cells comprise only 1-2% of the bipolar cell population, and their dendrites selectively contact S-opsin-expressing cones. In the dorsal half of the mouse retina, only 3-5% of the cones express S-opsin, and they are all contacted by blue-cone bipolar cells, whereas all L-opsin-expressing cones (∼95%) are avoided. In the ventral mouse retina, the great majority of cones express both S- and L-opsin. They are not contacted by blue-cone bipolar cells. A minority of ventral cones express S-opsin only, and they are selectively contacted by blue-cone bipolar cells. We suggest that these are genuine S-cones. In contrast to the other cones, their pedicles contain only low amounts of cone arrestin. The blue-cone bipolar cells of the mouse retina and their cone selectivity are closely similar to primate blue-cone bipolars, and we suggest that they both represent the phylogenetically ancient color system of the mammalian retina.
Neuropeptide Y Protects against Methamphetamine-Induced Neuronal Apoptosis in the Mouse Striatum
Authors: Thiriet Nathalie , Deng Xiaolin , Solinas Marcello , Ladenheim Bruce , Curtis Wendy , Goldberg Steven R. , Palmiter Richard D. , Cadet Jean Lud
Published: June 2005

Methamphetamine (METH) is an illicit drug that causes neuronal apoptosis in the mouse striatum, in a manner similar to the neuronal loss observed in neurodegenerative diseases. In the present study, injections of METH to mice were found to cause the death of enkephalin-positive projection neurons but not the death of neuropeptide Y (NPY)/nitric oxide synthase-positive striatal interneurons. In addition, these METH injections were associated with increased expression of neuropeptide Y mRNA and changes in the expression of the NPY receptors Y1and Y2. Administration of NPY in the cerebral ventricles blocked METH-induced apoptosis, an effect that was mediated mainly by stimulation of NPY Y2receptors and, to a lesser extent, of NPY Y1receptors. Finally, we also found that neuropeptide Y knock-out mice were more sensitive than wild-type mice to METH-induced neuronal apoptosis of both enkephalin- and nitric oxide synthase-containing neurons, suggesting that NPY plays a general neuroprotective role within the striatum. Together, our results demonstrate that neuropeptide Y belongs to the class of factors that maintain neuronal integrity during cellular stresses. Given the similarity between the cell death patterns induced by METH and by disorders such as Huntington's disease, our results suggest that NPY analogs might be useful therapeutic agents against some neurodegenerative processes.
Traumatic Stress Symptoms in Adolescent Organ Transplant Recipients
Authors: Mintzer Lisa Libman , Stuber Margaret L. , Seacord Debra , Castaneda Marleen , Mesrkhani Violet , Glover Dorie
Published: June 2005

Objective. Symptoms of posttraumatic stress disorder (PTSD) after life-threatening medical illness have been found to predict poor outcome in preliminary studies of adults and children. However, these symptoms are rarely recognized in general medical or pediatric settings. Here we report on the first large investigation to assess prevalence and correlates of self-reported symptoms of posttraumatic stress in a nonreferred sample of adolescent liver, heart, and kidney transplant recipients.

Methods. One hundred four adolescents, ages 12 to 20 years (mean: 15.7; SD: 2.1), completed and returned the University of California, Los Angeles, PTSD Index for the Diagnostic and Statistical Manual of Mental Disorders. All participants were at least 1 year post-initial transplant and were fluent speakers of English and/or Spanish.

Results. More than 16% of the adolescents met all symptom criteria for PTSD, and an additional 14.4% met 2 of 3 symptom-cluster criteria. Regression analysis indicated no effect of gender, ethnicity, age at interview, organ type, time since transplant, or age at transplant.

Conclusions. As has been found with other life-threatening pediatric conditions, solid organ transplantation can precipitate symptoms of posttraumatic stress. Symptoms are not predicted by what would be considered objective factors increasing life threat, suggesting a greater salience of subjective appraisal of threat, as has been seen in studies of childhood cancer survivors.
Factors Associated With Sensorineural Hearing Loss Among Survivors of Extracorporeal Membrane Oxygenation Therapy
Authors: Fligor Brian J. , Neault Marilyn W. , Mullen Charlotte H. , Feldman Henry A. , Jones Dwight T.
Published: June 2005

Objectives. To endeavor to explain why some graduates of extracorporeal membrane oxygenation (ECMO) therapy develop sensorineural hearing loss (SNHL) whereas others do not, to study the variability seen in the degree of SNHL, to attempt to explain why some graduates with SNHL experience progressive worsening whereas others do not, and to describe the time course of the onset of SNHL on the basis of identified risk factors.

Design. A retrospective chart review with proportional-hazards regression analysis to identify specific risk factors for SNHL from a list of patient and treatment variables.

Setting. Children’s Hospital Boston, a pediatric tertiary-care facility and ECMO center.

Patients. Neonatal ECMO graduates born in 1986–1994 who survived to discharge and underwent audiologic evaluations (n = 111) and a random sample of ECMO graduates who survived to discharge and did not undergo audiologic evaluations (n = 30).

Outcome Measures. Audiologic data, including the presence or absence of SNHL, the severity of SNHL at the most recent evaluation, the stability or progressive worsening of hearing (with the first evaluation compared with the most recent evaluation), and the occurrence of delayed-onset SNHL.

Results. Twenty-nine (26%) of 111 ECMO graduates who underwent audiologic testing had SNHL at the last evaluation. Of these 29 subjects with SNHL, 21 (72%) had progressive SNHL, of whom 14 (48%) had delayed-onset SNHL. The age of identification of SNHL ranged from 4 months to 8 years 11 months. Factors identified with proportional-hazards regression analyses as being associated significantly with the time to onset of SNHL were a primary diagnosis of congenital diaphragmatic hernia (hazard ratio: 2.60), length of ECMO therapy (hazard ratio: 7.18), and number of days children received aminoglycoside antibiotics (hazard ratio: 5.56). Kaplan-Meier “time-to-event” curves were constructed to illustrate the time course of onset of SNHL, as affected by each of the variables identified as significant risk factors.

Conclusions. These findings illustrate the need for early, routine, audiologic evaluations throughout childhood for all ECMO graduates. Children at even greater risk for developing SNHL because of a history of congenital diaphragmatic hernia, prolonged ECMO therapy, and/or a lengthy course of aminoglycoside antibiotic therapy should be monitored even more closely throughout childhood, depending on the child’s individual risk indicators, as suggested here. On the basis of these risk indicators, efforts can be made to minimize the risk of hearing loss while a child is being treated with ECMO. In addition, these risk indicators can assist with counseling families of ECMO graduates regarding the child’s specific risk of developing SNHL and how it can be managed should it occur.
Effects of Child Age and Body Size on Serious Injury From Passenger Air-Bag Presence in Motor Vehicle Crashes
Authors: Newgard Craig D. , Lewis Roger J.
Published: June 2005

Background. Current recommendations regarding children traveling in passenger vehicles equipped with passenger air bags are based, in part, on evidence that the air-bag–related risk of injury and death is higher for children ≤12 years of age. However, the age or body size required to allow a child to be seated safely in front of a passenger air bag is unknown.

Objective. To evaluate specific cutoff points for age, height, and weight as effect modifiers of the association between the presence of a passenger air bag and serious injury among children involved in motor vehicle crashes (MVCs), while controlling for important crash factors.

Design. A national population-based cohort of children involved in MVCs and included in the National Automotive Sampling System (NASS) Crashworthiness Data System (CDS) database from 1995 to 2002 was studied. NASS CDS clusters, strata, and weights were included in all analyses.

Subjects. Children 0 to 18 years of age involved in MVCs and seated in the right front passenger seat.

Main Outcome Measure. Serious injury, defined as an Abbreviated Injury Scale score of ≥3 for any body region.

Results. A total of 3790 patients (1 month to 18 years of age) were represented in the NASS CDS database during the 8-year period. Sixty children (1.6%) were seriously injured (Abbreviated Injury Scale score of ≥3). Among age, height, and weight, age of 0 to 14 years (versus 15–18 years) was the only consistent effect modifier of the association between air-bag presence (or air-bag deployment) and serious injury, particularly for crashes with a moderate probability of injury. In analyses stratified according to age and adjusted for important crash factors, children 0 to 14 years of age involved in frontal collisions seemed to be at increased risk of serious injury from air-bag presence (odds ratio [OR]: 2.66; 95% confidence interval [CI]: 0.23–30.9) and deployment (OR: 6.13; 95% CI: 0.30–126), although these values did not reach statistical significance. Among children 15 to 18 years of age involved in frontal collisions, there was a protective effect on injury from both air-bag presence (OR: 0.19; 95% CI: 0.05–0.75) and deployment (OR: 0.31; 95% CI: 0.09–0.99). These findings persisted in analyses involving all collision types. We did not identify similar cutoff points for height or weight.

Conclusions. Children up to 14 years of age may be at risk for serious preventable injury when seated in front of a passenger air bag, and children 15 to 18 years of age seem to experience protective effects of air-bag presence and deployment. Age may be a better marker than height or weight for risk assessment regarding children and air bags.
Femur Fractures Resulting From Stair Falls Among Children: An Injury Plausibility Model
Authors: Pierce Mary Clyde , Bertocci Gina E. , Janosky Janine E. , Aguel Fernando , Deemer Ernest , Moreland Morey , Boal Danielle K. B. , Garcia Sylvia , Herr Sandra , Zuckerbraun Noel , Vogeley Eva
Published: June 2005

Background. Stair falls are common among young children and are also common false histories in cases of child abuse. When a child presents with a femur fracture and a stair-fall history, a judgment of plausibility must be made. A lack of objective injury and biomechanical data makes plausibility determination more difficult. Our objective was to characterize key features associated with femur fractures from reported stair falls, to develop a model for assessing injury plausibility (IP).

Methods. Children 2 to 36 months of age who presented with a femur fracture from a reported stair fall were studied prospectively. Detailed history recording, examinations, fracture characterization, and injury scene analyses were conducted, and biomechanical measures associated with injury prediction were calculated. With our proposed IP model, all cases were then scored for the detail of history, biomechanical compatibility of fracture morphologic features, time to seeking care, and presence of other injuries.

Results. Twenty-nine children were diagnosed with a femur fracture resulting from a reported stair fall. The IP model made a clear distinction between 2 groups, designated plausible and suspicious. Significant differences were observed for the detail of history, biomechanical compatibility of fracture, time to seeking care, presence of other injuries, and total IP scores. In the plausible group, the minimal linear momentum associated with a transverse fracture was almost 10-fold greater than that for spiral or buckle fracture types.

Conclusions. This study adds new information to the current body of knowledge regarding injury biomechanics and fractures among children. The IP model provides an objective means of assessing plausibility of reported stair-fall–related femur fractures and identifies key characteristics to facilitate decision-making.
The Impact of Severe Respiratory Syncytial Virus on the Child, Caregiver, and Family During Hospitalization and Recovery
Authors: Leidy Nancy Kline , Margolis Mary Kay , Marcin James P. , Flynn Jennifer A. , Frankel Lorry R. , Johnson Susan , Langkamp Diane , Simoes Eric A. F.
Published: June 2005

Objective. To quantify the magnitude of child, caregiver, and family distress associated with hospitalization for severe respiratory syncytial virus (RSV) and the posthospitalization recovery period.

Design. A prospective study of 46 RSV-hospitalized infants and children ≤30 months of age with a history of prematurity (gestational age of ≤35 weeks) and 45 age-matched control subjects was performed. RSV group data were gathered during hospitalization and on days 4, 14, 21, and 60 after discharge; control group data were collected at the end of the RSV season and 60 days thereafter.

Main Outcome Measures. RSV severity; caregiver's rating of the child's health (100-point rating) and functional status (Functional Status IIR); caregiver health, stress (7-point rating), and anxiety (Spielberger State Anxiety Inventory); and family health and functioning (Family Adaptability and Cohesion Evaluation Scale II) were recorded.

Results. The mean age of the sample was 10.2 months; 51% of the subjects were male. The average duration of hospital stay for the RSV group was 5.8 ± 8 days. Most patients received supplemental oxygen (76%) and were monitored for apnea (60%). The mean age of the caregivers (93% mothers) was 29 years. During hospitalization, the RSV-infected patients' health and functional status were significantly poorer than those of control subjects. Caregivers of RSV-infected children reported more stress, greater anxiety, poorer health, and poorer family health and functioning. As long as 60 days after discharge, caregivers of RSV-infected children reported the children's health as significantly poorer and were personally more anxious, compared with control subjects.

Conclusions. RSV-related hospitalization creates significant distress for infants and children, caregivers, and families, with some effects extending as long as 60 days after discharge.