bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal cancer screening
Authors: Graf Bethan , Martin John
Published: October 2011

Colorectal cancer is theoretically a preventable disease and is ideally suited to a population screening programme, as there is a long premalignant phase, during which there is ample opportunity to intervene with a variety of different screening modalities. In this article, the authors review the alternative tests for colorectal cancer screening and discuss the rationale behind the Bowel Cancer Screening Programme in England. Copyright © 2011 Wiley Interface Ltd
Wrong‐side/site surgery
Authors: Challacombe Ben , Dasgupta Prokar , Amoroso Peter , Kirby Roger
Published: October 2011

With the recent increased focus on patient safety, various measures have been put in place to make it very difficult to perform wrong‐site or wrong‐side surgery. Copyright © 2011 Wiley Interface Ltd
Professor John P. Blandy, 1927–2011
Authors: Joyce Adrian
Published: October 2011

We note with great regret the passing of one of the UK's finest urologists. Copyright © 2011 Wiley Interface Ltd
Meeting the Challenge of Perioperative Education
Authors: Martin Karen K.
Published: October 2011

The staffing challenges faced by perioperative nurse managers today are not easily met by waiting for experienced perioperative nurses to apply for positions. As Baby Boomer nurses retire, managers must consider hiring and orienting new graduates and nurses experienced in other subspecialties who are interested in working in the OR. An effective didactic and clinical education program can produce nurses with a basic perioperative knowledge from which they can build a solid clinical practice. Using Periop 101: A Core Curriculum™, the director of perioperative services at a level II trauma center implemented a successful program to solve a staffing need and help students gain the knowledge and skills necessary to become effective perioperative nurses. Strong interest from capable applicants, a dedicated educator, and financial resources and support from hospital administrators helped make this program a viable way to staff the OR.
The Utilisation of Radiology for the Teaching of Anatomy in Canadian Medical Schools
Authors: Jack Andrew , Burbridge Brent
Published: October 2011

Objective

To determine the utilisation of diagnostic imaging (radiology) as a department and/or imaging medium in the teaching of anatomy at the Canadian undergraduate medical education level.

Methods

The study objectives were achieved through the use of a questionnaire and a literature review. The anatomy department head at each English-based Canadian Medical School was contacted, and the individual most responsible for anatomy teaching in the medical school curriculum was identified. This individual was subsequently asked to complete a questionnaire that evaluated the involvement of radiology for anatomy teaching in their curriculum.

Results

The use and integration of radiology is a common practice in the teaching of anatomy in Canadian undergraduate medicine. Although the methods and extent of its use varied among institutions, every English-based Canadian medical school, except one, was using diagnostic imaging material in their instruction of anatomy. Furthermore, half of the institutions had a radiologist as a faculty member of their anatomy department to help teach and to use imaging to its full potential.

Discussion

This audit of anatomy departments suggests that diagnostic imaging has an important role to play in anatomy teaching in Canadian English-speaking medical schools.
ASYMPTOTIC RESULTS FOR THE NUMBER OF PATHS IN A GRID
Authors: PANHOLZER ALOIS , PRODINGER HELMUT
Published: October 2011

In two recent papers, Albrecht and White [‘Counting paths in a grid’,Austral. Math. Soc. Gaz.35(2008), 43–48] and Hirschhorn [‘Comment on “Counting paths in a grid”’,Austral. Math. Soc. Gaz.36(2009), 50–52] considered the problem of counting the total numberPm,nof certain restricted lattice paths in anm×ngrid of cells, which appeared in the context of counting train paths through a rail network. Here we give a precise study of the asymptotic behaviour of these numbers for the square grid, extending the results of Hirschhorn, and furthermore provide an asymptotic equivalent of these numbers for a rectangular grid with a constant proportionα=m/nbetween the side lengths.
OPTIMIZATION OF MATRIX SEMIRINGS FOR CLASSIFICATION SYSTEMS
Authors: GAO D. Y. , KELAREV A. V. , YEARWOOD J. L.
Published: October 2011

The max-plus algebra is well known and has useful applications in the investigation of discrete event systems and affine equations. Structural matrix rings have been considered by many authors too. This article introduces more general structural matrix semirings, which include all matrix semirings over the max-plus algebra. We investigate properties of ideals in this construction motivated by applications to the design of centroid-based classification systems, or classifiers, as well as multiple classifiers combining several initial classifiers. The first main theorem of this paper shows that structural matrix semirings possess convenient visible generating sets for ideals. Our second main theorem uses two special sets to determine the weights of all ideals and describe all matrix ideals with the largest possible weight, which are optimal for the design of classification systems.
Longing for Elsewhere: Guaraní Reterritorializations
Authors: Gordillo Gastón
Published: October 2011

In September 2003, dozens of Guaraní families from the town of Hipólito Yrigoyen in northwest Argentina decided to take back La Loma, the forested hill that stands at the edge of town and from where they had been expelled decades earlier by the San Martín del Tabacal sugar plantation. On the verge of a cliff from where they could see the town and behind it the sugarcane fields, men, women, and children began clearing a space near their old cemetery in order to plant and begin building homes. In their makeshift camp, people raised an Argentinean flag and erected signs that read “Our Land” and “Argentinean Land.” The participants in the takeover whom I talked to a few months later remembered that their return to La Loma generated an enormous collective enthusiasm and the hope of living “like before,” working the land, raising animals, and free from the urban poverty and overcrowding of Hipólito Yrigoyen. However, six days later, when over a hundred people had gathered in the dark around a bonfire, police officers stormed the place shouting, “Move out!” Some officers accused them of being “undocumented Bolivians”; others asked where the Argentinean flag was, offended the flag was there. Twenty men and two women were arrested, handcuffed, and forced to walk single file down the hill, in an atmosphere of screams and scuffles that included shots in the air and the beating of a young man. A person from the community recalled what the plantation spokesperson subsequently said about their claim, based on the fact that many of their ancestors were plantation workers who came from Bolivia: “What do these immigrants think they're asking for? They should go ask for land in Bolivia.”
Self-focusing of laser beam in collisional plasma and its effect on Second Harmonic generation
Authors: Singh Arvinder , Walia Keshav
Published: October 2011

This paper presents an investigation of self-focusing of Gaussian laser beam in collisional plasma and its effect on second harmonic generation. Due to non-uniform heating, collisional non-linearity arises, which leads to redistribution of carriers and hence affects the plasma wave, which in turn affects the second harmonic generation. Effect of the intensity of the laser beam/plasma density on the harmonic yield is studied in detail. We have set up the non-linear differential equations for the beam width parameters of the main beam, plasma wave, second harmonic generation and second harmonic yield by taking full non-linear part of the dielectric constant of collisional plasma with the help of moment theory approach. It is predicted from the analysis that harmonic yield increases/decreases due to increase in the plasma density/intensity of the laser beam respectively.
Predictors of anaemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections
Authors: Finkelstein Julia L , Mehta Saurabh , Duggan Christopher P , Spiegelman Donna , Aboud Said , Kupka Roland , Msamanga Gernard I , Fawzi Wafaie W
Published: October 2011

Objective

Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania.

Design

Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period.

Setting

Antenatal clinics in Dar es Salaam, Tanzania.

Subjects

Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995–1997).

Results

Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1·4 and 2·3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period.

Conclusions

Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings – particularly during the pre- and postpartum periods.
The causality analysis of climate change and large-scale human crisis
Authors: Zhang David D. , Lee Harry F. , Wang Cong , Li Baosheng , Pei Qing , Zhang Jane , An Yulun
Published: October 2011

Recent studies have shown strong temporal correlations between past climate changes and societal crises. However, the specific causal mechanisms underlying this relation have not been addressed. We explored quantitative responses of 14 fine-grained agro-ecological, socioeconomic, and demographic variables to climate fluctuations from A.D. 1500–1800 in Europe. Results show that cooling from A.D. 1560–1660 caused successive agro-ecological, socioeconomic, and demographic catastrophes, leading to the General Crisis of the Seventeenth Century. We identified a set of causal linkages between climate change and human crisis. Using temperature data and climate-driven economic variables, we simulated the alternation of defined “golden” and “dark” ages in Europe and the Northern Hemisphere during the past millennium. Our findings indicate that climate change was the ultimate cause, and climate-driven economic downturn was the direct cause, of large-scale human crises in preindustrial Europe and the Northern Hemisphere.
Acoustic interference and recognition space within a complex assemblage of dendrobatid frogs
Authors: Amézquita Adolfo , Flechas Sandra Victoria , Lima Albertina Pimentel , Gasser Herbert , Hödl Walter
Published: October 2011

In species-rich assemblages of acoustically communicating animals, heterospecific sounds may constrain not only the evolution of signal traits but also the much less-studied signal-processing mechanisms that define the recognition space of a signal. To test the hypothesis that the recognition space is optimally designed, i.e., that it is narrower toward the species that represent the higher potential for acoustic interference, we studied an acoustic assemblage of 10 diurnally active frog species. We characterized their calls, estimated pairwise correlations in calling activity, and, to model the recognition spaces of five species, conducted playback experiments with 577 synthetic signals on 531 males. Acoustic co-occurrence was not related to multivariate distance in call parameters, suggesting a minor role for spectral or temporal segregation among species uttering similar calls. In most cases, the recognition space overlapped but was greater than the signal space, indicating that signal-processing traits do not act as strictly matched filters against sounds other than homospecific calls. Indeed, the range of the recognition space was strongly predicted by the acoustic distance to neighboring species in the signal space. Thus, our data provide compelling evidence of a role of heterospecific calls in evolutionarily shaping the frogs' recognition space within a complex acoustic assemblage without obvious concomitant effects on the signal.
Discovery of the recoverable high-pressure iron oxide Fe4O5
Authors: Lavina Barbara , Dera Przemyslaw , Kim Eunja , Meng Yue , Downs Robert T. , Weck Philippe F. , Sutton Stephen R. , Zhao Yusheng
Published: October 2011

Phases of the iron–oxygen binary system are significant to most scientific disciplines, directly affecting planetary evolution, life, and technology. Iron oxides have unique electronic properties and strongly interact with the environment, particularly through redox reactions. The iron–oxygen phase diagram therefore has been among the most thoroughly investigated, yet it still holds striking findings. Here, we report the discovery of an iron oxide with formula Fe4O5, synthesized at high pressure and temperature. The previously undescribed phase, stable from 5 to at least 30 GPa, is recoverable to ambient conditions. First-principles calculations confirm that the iron oxide here described is energetically more stable than FeO + Fe3O4at pressure greater than 10 GPa. The calculated lattice constants, equation of states, and atomic coordinates are in excellent agreement with experimental data, confirming the synthesis of Fe4O5. Given the conditions of stability and its composition, Fe4O5is a plausible accessory mineral of the Earth’s upper mantle. The phase has strong ferrimagnetic character comparable to magnetite. The ability to synthesize the material at accessible conditions and recover it at ambient conditions, along with its physical properties, suggests a potential interest in Fe4O5for technological applications.
Distinct patterns of
Period
gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays
Authors: Schwartz William J. , Tavakoli-Nezhad Mahboubeh , Lambert Christopher M. , Weaver David R. , de la Iglesia Horacio O.
Published: October 2011

The circadian clock in the mammalian hypothalamic suprachiasmatic nucleus (SCN) is entrained by the ambient light/dark cycle, which differentially acts to cause the clock to advance or delay. Light-induced changes in the rhythmic expression of SCN clock genes are believed to be a critical step in this process, but how the two entrainment modalities—advances vs. delays—engage the molecular clockwork remains incompletely understood. We investigated molecular substrates of photic entrainment of the clock in the SCN by stably entraining hamsters to T cycles (non–24-h light/dark cycles) consisting of a single 1-h light pulse repeated as either a short (23.33-h) or a long (24.67-h) cycle; under these conditions, the light pulse of the short cycle acts as “dawn,” whereas that of the long cycle acts as “dusk.” Analyses of the expression of the photoinducible and rhythmic clock genes
Period 1
and
2
(
Per1
and
Per2
) in the SCN revealed fundamental differences under these two entrainment modes. Light at dawn advanced the clock, advancing the onset of the
Per1
mRNA rhythm and acutely increasing mRNA transcription, whereas light at dusk delayed the clock, delaying the offset of the
Per2
mRNA rhythm and tonically increasing mRNA stability. The results suggest that the underlying molecular mechanisms of circadian entrainment differ with morning (advancing) or evening (delaying) light exposure, and such differences may reflect how entrainment takes place in nocturnal animals under natural conditions.
Full p53 transcriptional activation potential is dispensable for tumor suppression in diverse lineages
Authors: Jiang Dadi , Brady Colleen A. , Johnson Thomas M. , Lee Eunice Y. , Park Eunice J. , Scott Matthew P. , Attardi Laura D.
Published: October 2011

Over half of all human cancers, of a wide variety of types, sustain mutations in the
p53
tumor suppressor gene. Although p53 limits tumorigenesis through the induction of apoptosis or cell cycle arrest, its molecular mechanism of action in tumor suppression has been elusive. The best-characterized p53 activity in vitro is as a transcriptional activator, but the identification of numerous additional p53 biochemical activities in vitro has made it unclear which mechanism accounts for tumor suppression. Here, we assess the importance of transcriptional activation for p53 tumor suppression function in vivo in several tissues, using a knock-in mouse strain expressing a p53 mutant compromised for transcriptional activation, p53
25,26
. p53
25,26
is severely impaired for the transactivation of numerous classical p53 target genes, including
p21, Noxa
, and
Puma
, but it retains the ability to activate a small subset of p53 target genes, including
Bax
. Surprisingly, p53
25,26
can nonetheless suppress tumor growth in cancers derived from the epithelial, mesenchymal, central nervous system, and lymphoid lineages. Therefore, full transactivation of most p53 target genes is dispensable for p53 tumor suppressor function in a range of tissue types. In contrast, a transcriptional activation mutant that is completely defective for transactivation, p53
25,26,53,54
, fails to suppress tumor development. These findings demonstrate that transcriptional activation is indeed broadly critical for p53 tumor suppressor function, although this requirement reflects the limited transcriptional activity observed with p53
25,26
rather than robust transactivation of a full complement of p53 target genes.
Double-core-hole spectroscopy for chemical analysis with an intense X-ray femtosecond laser
Authors: Berrah Nora , Fang Li , Murphy Brendan , Osipov Timur , Ueda Kiyoshi , Kukk Edwin , Feifel Raimund , van der Meulen Peter , Salen Peter , Schmidt Henning T. , Thomas Richard D. , Larsson Mats , Richter Robert , Prince Kevin C. , Bozek John D. , Bostedt Christoph , Wada Shin-ichi , Piancastelli Maria N. , Tashiro Motomichi , Ehara Masahiro
Published: October 2011

Theory predicts that double-core-hole (DCH) spectroscopy can provide a new powerful means of differentiating between similar chemical systems with a sensitivity not hitherto possible. Although DCH ionization on a single site in molecules was recently measured with double- and single-photon absorption, double-core holes with single vacancies on two different sites, allowing unambiguous chemical analysis, have remained elusive. Here we report that direct observation of double-core holes with single vacancies on two different sites produced via sequential two-photon absorption, using short, intense X-ray pulses from the Linac Coherent Light Source free-electron laser and compare it with theoretical modeling. The observation of DCH states, which exhibit a unique signature, and agreement with theory proves the feasibility of the method. Our findings exploit the ultrashort pulse duration of the free-electron laser to eject two core electrons on a time scale comparable to that of Auger decay and demonstrate possible future X-ray control of physical inner-shell processes.
Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism
Authors: Horev Guy , Ellegood Jacob , Lerch Jason P. , Son Young-Eun E. , Muthuswamy Lakshmi , Vogel Hannes , Krieger Abba M. , Buja Andreas , Henkelman R. Mark , Wigler Michael , Mills Alea A.
Published: October 2011

Recurrent copy number variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a “behavior trap” phenotype—a specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. These findings indicate that 16p11.2 CNVs cause brain and behavioral anomalies, providing insight into human neurodevelopmental disorders.
Regenerative Medicine and New Labour life science policy: rhetorics of success, narratives of sustainability and survival
Authors: Kewell B. , Beck M.
Published: October 2011

Advances in stem cell science and tissue engineering are being turned into applications and products through a novel medical paradigm known as regenerative medicine. This paper begins by examining the vulnerabilities and risks encountered by the regenerative medicine industry during a pivotal moment in its scientific infancy: the 2000s. Under the auspices of New Labour, British medical scientists and life science innovation firms associated with regenerative medicine, received demonstrative rhetorical pledges of support, aligned with the publication of a number of government initiated reports presaged by Bioscience 2015: Improving National Health, Increasing National Wealth. The Department of Health and the Department of Trade and Industry (and its successors) held industry consultations to determine the best means by which innovative bioscience cultures might be promoted and sustained in Britain. Bioscience 2015 encapsulates the first chapter of this sustainability narrative. By 2009, the tone of this storyline had changed to one of survivability. In the second part of the paper, we explore the ministerial interpretation of the ‘bioscience discussion cycle’ that embodies this narrative of expectation, using a computer-aided content analysis programme. Our analysis notes that the ministerial interpretation of these reports has continued to place key emphasis upon the distinctive and exceptional characteristics of the life science industries, such as their ability to perpetuate innovations in regenerative medicine and the optimism this portends – even though many of the economic expectations associated with this industry have remained unfulfilled.
Managing innovation in the stem cell sciences: Australian views from the field
Authors: Harvey Olivia
Published: October 2011

Recent research has shown that governments around the world are implementing a range of strategies intended to maximise national competitive advantage in the growing global stem cell bioeconomy. There are two reasons for this: on the one hand, the global expansion in neoliberal economic policy since the 1970s has resulted in an increasing reliance on the free-market economy for national growth and prosperity; and on the other hand, the crisis of the ageing population and the spiralling costs of healthcare have placed increasing pressures on governments to rationalise precious resources. By indicating support for the growth of nationally competitive industries in a new technology that promises to revolutionise healthcare, such as stem cell science, governments are able to meet the twin demands of neoliberal economic policy and care for the health of national populations. The governments of the UK, China, India, Singapore and Australia were among the first to develop deliberate strategies designed to enhance their local and regional stem cell industries. While most strategies contain quite similar elements, there is yet to be any systematic evaluation of how effective they might be at building support for the stem cell industries. Drawing on interviews conducted in 2009, this paper will examine how stakeholders engaged in the stem cell sciences in one of these locations – Australia – view the effectiveness of state strategies from the front-line of the stem cell innovation process. The aim here is to identify what evidence exists to support specific strategy development.
ProfileChaser: searching microarray repositories based on genome-wide patterns of differential expression
Authors: Engreitz Jesse M. , Chen Rong , Morgan Alexander A. , Dudley Joel T. , Mallelwar Rohan , Butte Atul J.
Published: October 2011

Summary: We introduce ProfileChaser, a web server that allows for querying the Gene Expression Omnibus based on genome-wide patterns of differential expression. Using a novel, content-based approach, ProfileChaser retrieves expression profiles that match the differentially regulated transcriptional programs in a user-supplied experiment. This analysis identifies statistical links to similar expression experiments from the vast array of publicly available data on diseases, drugs, phenotypes and other experimental conditions.

Availability:  http://profilechaser.stanford.edu

Contact:  abutte@stanford.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Strategy-dependent Dissociation of the Neural Correlates Involved in Pain Modulation
Authors: Lawrence Jane M. , Hoeft Fumiko , Sheau Kristen E. , Mackey Sean C.
Published: October 2011

Background

Cognitive strategies are a set of psychologic behaviors used to modulate one's perception or interpretation of a sensation or situation. Although the effectiveness of each cognitive strategy seems to differ between individuals, they are commonly used clinically to help patients with chronic pain cope with their condition. The neural basis of commonly used cognitive strategies is not well understood. Understanding the neural correlates that underlie these strategies will enhance understanding of the analgesic network of the brain and the cognitive modulation of pain.

Methods

The current study examines patterns of brain activation during two common cognitive strategies, external focus of attention and reappraisal, in patients with chronic pain using functional magnetic resonance imaging.

Results

Behavioral results revealed interindividual variability in the effectiveness of one strategy versus another in the patients. Functional magnetic resonance imaging revealed distinct patterns of activity when the two strategies were used. During external focus of attention, activity was observed mainly in cortical areas including the postcentral gyrus, inferior parietal lobule, middle occipital gyrus, and precentral gyrus. The use of reappraisal evoked activity in the thalamus and amygdala in addition to cortical regions. Only one area, the postcentral gyrus, was observed to be active during both strategies.

Conclusions

The results of this study suggest that different cognitive behavioral strategies recruit different brain regions to perform the same task: pain modulation.
Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics
Authors: Pick Jeremy , Chen Yihan , Moore Jason T. , Sun Yi , Wyner Abraham J. , Friedman Eliot B. , Kelz Max B.
Published: October 2011

Background

General anesthesia has been likened to a state in which anesthetized subjects are locked out of access to both rapid eye movement (REM) sleep and wakefulness. Were this true for all anesthetics, a significant REM rebound after anesthetic exposure might be expected. However, for the intravenous anesthetic propofol, studies demonstrate that no sleep debt accrues. Moreover, preexisting sleep debts dissipate during propofol anesthesia. To determine whether these effects are specific to propofol or are typical of volatile anesthetics, the authors tested the hypothesis that REM sleep debt would accrue in rodents anesthetized with volatile anesthetics.

Methods

Electroencephalographic and electromyographic electrodes were implanted in 10 mice. After 9-11 days of recovery and habituation to a 12 h:12 h light-dark cycle, baseline states of wakefulness, nonrapid eye movement sleep, and REM sleep were recorded in mice exposed to 6 h of an oxygen control and on separate days to 6 h of isoflurane, sevoflurane, or halothane in oxygen. All exposures were conducted at the onset of light.

Results

Mice in all three anesthetized groups exhibited a significant doubling of REM sleep during the first 6 h of the dark phase of the circadian schedule, whereas only mice exposed to halothane displayed a significant increase in nonrapid eye movement sleep that peaked at 152% of baseline.

Conclusion

REM sleep rebound after exposure to volatile anesthetics suggests that these volatile anesthetics do not fully substitute for natural sleep. This result contrasts with the published actions of propofol for which no REM sleep rebound occurred.
Methylphenidate Actively Induces Emergence from General Anesthesia
Authors: Solt Ken , Cotten Joseph F. , Cimenser Aylin , Wong Kin F. K. , Chemali Jessica J. , Brown Emery N.
Published: October 2011

Background

Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia.

Methods

Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia. They then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate-induced restoration of righting during continuous isoflurane general anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Intravenous droperidol was administered to test for inhibition of methylphenidate's actions.

Results

Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without methylphenidate compared with administration of methylphenidate was 200 [155-331] s (median, [95% CI]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta (less than 4 Hz) to theta (4-8 Hz), and induced an increase in minute ventilation. Administration of intravenous droperidol (0.5 mg/kg) before intravenous methylphenidate (5 mg/kg) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation.

Conclusions

Methylphenidate actively induces emergence from isoflurane general anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. The authors' findings suggest that methylphenidate may be useful clinically as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery.
Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat
Authors: Gauthier Elizabeth A. , Guzick Sarah E. , Brummett Chad M. , Baghdoyan Helen A. , Lydic Ralph
Published: October 2011

Background

Buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine concentrations in regions of the basal forebrain and pontine brainstem that regulate sleep.

Methods

Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep-wake states were recorded for 24 h. In additional rats, buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while adenosine was simultaneously measured.

Results

An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in nonrapid eye movement sleep (-22.1%) and rapid eye movement sleep (-3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative-hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine concentrations in the pontine reticular formation (-14.6%) and substantia innominata (-36.7%). Intravenous administration of buprenorphine significantly decreased (-20%) adenosine in the substantia innominata.

Conclusions

Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative-hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine concentrations in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.
General Anesthesia Causes Long-term Impairment of Mitochondrial Morphogenesis and Synaptic Transmission in Developing Rat Brain
Authors: Sanchez Victoria , Feinstein Shawn D. , Lunardi Nadia , Joksovic Pavle M. , Boscolo Annalisa , Todorovic Slobodan M. , Jevtovic-Todorovic Vesna
Published: October 2011

Background

Clinically used general anesthetics, alone or in combination, are damaging to the developing mammalian brain. In addition to causing widespread apoptotic neurodegeneration in vulnerable brain regions, exposure to general anesthesia at the peak of synaptogenesis causes learning and memory deficiencies later in life. In vivo rodent studies have suggested that activation of the intrinsic (mitochondria-dependent) apoptotic pathway is the earliest warning sign of neuronal damage, suggesting that a disturbance in mitochondrial integrity and function could be the earliest triggering events.

Methods

Because proper and timely mitochondrial morphogenesis is critical for brain development, the authors examined the long-term effects of a commonly used anesthesia combination (isoflurane, nitrous oxide, and midazolam) on the regional distribution, ultrastructural properties, and electron transport chain function of mitochondria, as well as synaptic neurotransmission, in the subiculum of rat pups.

Results

This anesthesia, administered at the peak of synaptogenesis, causes protracted injury to mitochondria, including significant enlargement of mitochondria (more than 30%, P < 0.05), impairment of their structural integrity, an approximately 28% increase in their complex IV activity (P < 0.05), and a twofold decrease in their regional distribution in presynaptic neuronal profiles (P < 0.05), where their presence is important for the normal development and functioning of synapses. Consequently, the authors showed that impaired mitochondrial morphogenesis is accompanied by heightened autophagic activity, decrease in mitochondrial density (approximately 27%, P < 0.05), and long-lasting disturbances in inhibitory synaptic neurotransmission. The interrelation of these phenomena remains to be established.

Conclusion

Developing mitochondria are exquisitely vulnerable to general anesthesia and may be important early target of anesthesia-induced developmental neurodegeneration.
Pharmacological Consequence of the A118G μ Opioid Receptor Polymorphism on Morphine- and Fentanyl-mediated Modulation of Ca2+Channels in Humanized Mouse Sensory Neurons
Authors: Mahmoud Saifeldin , Thorsell Annika , Sommer Wolfgang H. , Heilig Markus , Holgate Joan K. , Bartlett Selena E. , Ruiz-Velasco Victor
Published: October 2011

Background

The most common functional single nucleotide polymorphism of the human OPRM1 gene, A118G, has been shown to be associated with interindividual differences in opioid analgesic requirements, particularly with morphine, in patients with acute postoperative pain. The purpose of this study was to examine whether this polymorphism would modulate the morphine and fentanyl pharmacological profile of sensory neurons isolated from a humanized mouse model homozygous for either the 118A or 118G allele.

Methods

The coupling of wild-type and mutant μ opioid receptors to voltage-gated Ca channels after exposure to either ligand was examined by employing the whole cell variant of the patch-clamp technique in acutely dissociated trigeminal ganglion neurons. Morphine-mediated antinociception was measured in mice carrying either the 118AA or 118GG allele.

Results

The biophysical parameters (cell size, current density, and peak current amplitude potential) measured from both groups of sensory neurons were not significantly different. In 118GG neurons, morphine was approximately fivefold less potent and 26% less efficacious than that observed in 118AA neurons. On the other hand, the potency and efficacy of fentanyl were similar for both groups of neurons. Morphine-mediated analgesia in 118GG mice was significantly reduced compared with the 118AA mice.

Conclusions

This study provides evidence to suggest that the diminished clinical effect observed with morphine in 118G carriers results from an alteration of the receptor's pharmacology in sensory neurons. In addition, the impaired analgesic response with morphine may explain why carriers of this receptor variant have an increased susceptibility to become addicted to opioids.
Invasive and Concomitant Noninvasive Intraoperative Blood Pressure Monitoring
Authors: Wax David B. , Lin Hung-Mo , Leibowitz Andrew B.
Published: October 2011

Background

Noninvasive (NIBP) and intraarterial (ABP) blood pressure monitoring are used under different circumstances and may yield different values. The authors endeavored to characterize these differences and hypothesized that there could be differences in interventions associated with the use of ABP alone ([ABP]) versus ABP in combination with NIBP ([ABP+NIBP]).

Methods

Simultaneous measurements of ABP and NIBP made during noncardiac cases were extracted from electronic anesthesia records; the differences were subjected to regression analysis. Records of blood products, vasopressors, and antihypertensives administered were also extracted, and associations between the use of these therapies and monitoring strategy ([ABP] vs. [ABP+NIBP]) were tested using univariate, multivariate, and propensity score matched analyses.

Results

Among 24,225 cases, 63% and 37% used [ABP+NIBP] and [ABP], respectively. Systolic NIBP was likely to be higher than ABP when ABP was less than 111 mmHg and lower than ABP otherwise. Among patients with hypotension, transfusion occurred in 27% versus 43% of patients in the [ABP+NIBP] versus [ABP] group, respectively (odds ratio = 0.4; 95% CI 0.35-0.46), and 7% versus 18% of patients in the [ABP+NIBP] versus [ABP] group received vasopressor infusions, respectively (P < 0.01). Among hypertensive patients, 12% versus 44% of those in the [ABP+NIBP] versus [ABP] group received antihypertensive agents, respectively (P < 0.01).

Conclusions

NIBP was generally higher than ABP during periods of hypotension and lower than ABP during periods of hypertension. The use of NIBP measurements to supplement ABP measurements was associated with decreased use of blood transfusions, vasopressor infusions, and antihypertensive medications compared with the use of ABP alone.
Rewarding Electrical Brain Stimulation in Rats after Peripheral Nerve Injury
Authors: Ewan Eric E. , Martin Thomas J.
Published: October 2011

Background

Prescription opioid abuse is a significant concern in treating chronic pain, yet few studies examine how neuropathic pain alters the abuse liability of commonly abused prescription opioids.

Methods

Normal and spinal nerve ligated (SNL) rats were implanted with electrodes into the left ventral tegmental area (VTA). Rats were trained to lever press for intracranial electrical stimulation (VTA ICSS), and the effects of methadone, fentanyl, hydromorphone, and oxycodone on facilitation of VTA ICSS were assessed. A second group of neuropathic rats were implanted with intrathecal catheters, and the effects of intrathecal clonidine, adenosine, and gabapentin on facilitation of VTA ICSS were assessed. The effects of electrical stimulation of the VTA on mechanical allodynia were assessed in SNL rats.

Results

Responding for VTA ICSS was similar in control and SNL rats. Methadone, fentanyl, and hydromorphone were less potent in facilitating VTA ICSS in SNL rats. Oxycodone produced a significant facilitation of VTA ICSS in control (maximum shift 24.10 ± 6.19 Hz) but not SNL rats (maximum shift 16.32 ± 7.49 Hz), but also reduced maximal response rates in SNL rats. Intrathecal administration of clonidine, adenosine, and gabapentin failed to facilitate VTA ICSS in SNL rats, and electrical stimulation of the VTA did not alter mechanical allodynia following nerve injury.

Conclusions

The present data suggests that the positive reinforcing effects of commonly abused prescription opioids are diminished following nerve injury. In addition, alleviation of mechanical allodynia with nonopioid analgesics does not appear to stimulate limbic dopamine pathways originating from the VTA in SNL rats.
A 18F-fluorodeoxyglucose MicroPET Imaging Study to Assess Changes in Brain Glucose Metabolism in a Rat Model of Surgery-induced Latent Pain Sensitization
Authors: Romero Asunción , Rojas Santiago , Cabañero David , Gispert Juan D. , Herance José R. , Campillo Ana , Puig Margarita M.
Published: October 2011

Background

Neuroplastic changes involved in latent pain sensitization after surgery are poorly defined. We assessed temporal changes in glucose brain metabolism in a postoperative rat model using positron emission tomography. We also investigated brain metabolism after naloxone administration.

Methods

Rats were given remifentanil anesthetic and underwent a plantar incision, with 1 mg/kg of (-)-naloxone subcutaneously administered on postoperative days 20 and 21. Using the von Frey test, mechanical thresholds were measured pre- and postoperatively at different time points in awake animals during F-fluorodeoxyglucose (F-FDG) uptake. Brain images were also obtained the day before mechanical testing, using a positron emission tomography R4 scanner (Concorde Microsystems, Siemens, Knoxville, TN). Differences in brain activity were assessed utilizing a statistical parametric mapping.

Results

Surgery induced minor changes in F-FDG uptake in the cerebellum, hippocampus, and posterior cortex, which extended to the thalamus, hypothalamus, and brainstem on days 6 and 7. Changes were still present on day 21. Maximal postoperative hypersensitivity was observed on day 2. The administration of (-)-naloxone on day 21 induced significant hypersensitivity, greatly enhancing the effect on F-FDG uptake. In sham-operated rats, naloxone induced changes limited to the striatum and the cerebellum. Nonnociceptive stimulation with von Frey filaments had no effect on F-FDG uptake.

Conclusions

Surgery, remifentanil, and their combination induced long-lasting and significant metabolic changes in the pain brain matrix, with a positive correlation with hypersensitivity after naloxone. Changes in brain F-FDG precipitated by naloxone suggest that surgery under remifentanil anesthetic induces the greatest neuroplastic brain adaptations in opioid-related pathways involved in nociceptive processing and long-lasting pain sensitization.
Interactions between Nitrous Oxide and Tissue Plasminogen Activator in a Rat Model of Thromboembolic Stroke
Authors: Haelewyn Benoît , David Hélène N. , Colloc'h Nathalie , Colomb Denis G. , Risso Jean-Jacques , Abraini Jacques H.
Published: October 2011

Background

Preclinical evidence in rodents has suggested that inert gases, such as xenon or nitrous oxide, may be promising neuroprotective agents for treating acute ischemic stroke. This has led to many thinking that clinical trials could be initiated in the near future. However, a recent study has shown that xenon interacts with tissue-type plasminogen activator (tPA), a well-recognized approved therapy of acute ischemic stroke. Although intraischemic xenon inhibits tPA-induced thrombolysis and subsequent reduction of brain damage, postischemic xenon virtually suppresses both ischemic brain damage and tPA-induced brain hemorrhages and disruption of the blood-brain barrier. The authors investigated whether nitrous oxide could also interact with tPA.

Methods

The authors performed molecular modeling of nitrous oxide binding on tPA, characterized the concentration-dependent effects of nitrous oxide on tPA enzymatic and thrombolytic activity in vitro, and investigated the effects of intraischemic and postischemic nitrous oxide in a rat model of thromboembolic acute ischemic stroke.

Results

The authors demonstrate nitrous oxide is a tPA inhibitor, intraischemic nitrous oxide dose-dependently inhibits tPA-induced thrombolysis and subsequent reduction of ischemic brain damage, and postischemic nitrous oxide reduces ischemic brain damage, but in contrast with xenon, it increases brain hemorrhages and disruption of the blood-brain barrier.

Conclusions

In contrast with previous studies using mechanical acute stroke models, these data obtained in a clinically relevant rat model of thromboembolic stroke indicate that nitrous oxide should not be considered a good candidate agent for treating acute ischemic stroke compared with xenon.