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Sevrioukova IF
Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697-3900, USA. sevrioui@uci.edu
Redox-linked conformational dynamics in apoptosis-inducing factor.
J Mol Biol. 2009 Jul 31;390(5):924-38
Apoptosis-inducing factor (AIF) is a bifunctional mitochondrial flavoprotein critical for energy metabolism and induction of caspase-independent apoptosis, whose exact role in normal mitochondria remains unknown. Upon reduction with NADH, AIF undergoes dimerization and forms tight, long-lived FADH(2)-NAD charge-transfer complexes (CTC) that are proposed to be functionally important. To obtain a deeper insight into structure/function relations and redox mechanism of this vitally important protein, we determined the X-ray structures of oxidized and NADH-reduced forms of naturally folded recombinant murine AIF. Our structures reveal that CTC with the pyridine nucleotide is stabilized by (i) pi-stacking interactions between coplanar nicotinamide, isoalloxazine, and Phe309 rings; (ii) rearrangement of multiple aromatic residues in the C-terminal domain, likely serving as an electron delocalization site; and (iii) an extensive hydrogen-bonding network involving His453, a key residue that undergoes a conformational switch to directly interact with and optimally orient the nicotinamide for charge transfer. Via the His453-containing peptide, redox changes in the active site are transmitted to the surface, promoting AIF dimerization and restricting access to a primary nuclear localization signal through which the apoptogenic form is transported to the nucleus. Structural findings agree with biochemical data and support the hypothesis that both normal and apoptogenic functions of AIF are controlled by NADH.
PMID: 19447115

Vilcins IM,Old JM,Deane E
Department of Biological Sciences, E8A, Macquarie University, NSW, 2109, Australia. ivilcins@uci.edu.au
Detection of a Hepatozoon and spotted fever group Rickettsia species in the common marsupial tick (Ixodes tasmani) collected from wild Tasmanian devils (Sarcophilus harrisii), Tasmania.
Vet Parasitol. 2009 May 26;162(1-2):23-31
Tasmanian devils are the largest extant marsupial carnivores, confined to the Australian island state of Tasmania. The iconic marsupial has dramatically declined in number since the discovery of devil facial tumor disease in 1996 and efforts are being made to uncover vital information to assist in the long-term survival of the species. Ticks are the main vectors of arthropod-borne disease in animals, raising the question of whether Tasmanian devils may be host to arthropods capable of harboring infectious agents. Partially engorged ticks were collected from 35 wild Tasmanian devils and tested for the presence of a range of tick-borne genera. A spotted fever group Rickettsia was detected in 45.5% of samples of the tick Ixodes tasmani (n=44), from all trapping locations, sharing close sequence identity to members of the Rickettsia massiliae group. A Hepatozoon species was also identified in 34.1% of the same sample set, sharing sequence similarities to Hepatozoon felis, a known pathogen of felids. Dual detection was identified in 13.6% of tick samples, where prevalence of the two genera overlapped. The existence of two previously undetected species of genera known for containing pathogens identifies additional potential risks to the health of the devil population.
PMID: 19303711

Hipp JR,Jannetta J,Shah R,Turner S
Department of Criminology, Law and Society, University of California, Irvine, CA 92697, USA. john.hipp@UCI.edu
Parolees' physical closeness to health service providers: a study of California parolees.
Health Place. 2009 Sep;15(3):649-58
We studied a sample of parolees and health service providers in the state of California in 2005-2006 to examine the relative physical closeness to health providers (and the potential demand of these providers) of parolees based on their demographic and prior offending characteristics. Although African-American and Latino parolees have more health providers nearby, these providers have considerably more potential demand. The health providers near long-term prisoners and sex offenders have more potential demand. The results suggest inequity in access to services, as minority parolees and those with greater needs may live near more impacted providers. The results also suggest some differences in access based on rural, suburban, or urban location.
PMID: 19119053

Penner AM
Department of Sociology, University of California, Irvine, California 92697-5100, USA. andrew.penner@uci.edu
Gender differences in extreme mathematical achievement: an international perspective on biological and social factors.
AJS. 2008;114 Suppl:S138-70
Genetic and other biological explanations have reemerged in recent scholarship on the underrepresentation of women in mathematics and the sciences. This study engages this debate by using international data-including math achievement scores from the Third International Mathematics and Sciences Study and country-level data from the World Bank, the United Nations, the International Labour Organization, the World Values Survey, and the International Social Survey Programme-to demonstrate the importance of social factors and to estimate an upper bound for the impact of genetic factors. The author argues that international variation provides a valuable opportunity to present simple and powerful arguments for the continued importance of social factors. In addition, where previous research has, by and large, focused on differences in population means, this work examines gender differences throughout the distribution. The article shows that there is considerable variation in gender differences internationally, a finding not easily explained by strictly biological theories. Modeling the cross-national variation in gender differences with country-level predictors reveals that differences among high achievers are related to gender inequality in the labor market and differences in the overall status of men and women.
PMID: 19569403

Potkin SG,Turner JA,Guffanti G,Lakatos A,Torri F,Keator DB,Macciardi F
Department of Psychiatry and Human Behavior, University California of Irvine, Irvine, CA, USA. sgpotkin@uci.edu
Genome-wide strategies for discovering genetic influences on cognition and cognitive disorders: methodological considerations.
Cogn Neuropsychiatry. 2009;14(4-5):391-418
INTRODUCTION: Genes play a well-documented role in determining normal cognitive function. This paper focuses on reviewing strategies for the identification of common genetic variation in genes that modulate normal and abnormal cognition with a genome-wide association scan (GWAS). GWASs make it possible to survey the entire genome to discover important but unanticipated genetic influences. METHODS: The use of a quantitative phenotype in combination with a GWAS provides many advantages over a case-control design, both in power and in physiological understanding of the underlying cognitive processes. We review the major features of this approach, and show how, using a General Linear Model method, the contribution of each Single Nucleotide Polymorphism (SNP) to the phenotype is determined, and adjustments then made for multiple tests. An example of the strategy is presented, in which fMRI measures of cortical inefficiency while performing a working memory task are used as the quantitative phenotype. We estimate power under different effect sizes (10-30%) and variations in allelic frequency for a Quantitative Trait (QT) (10-20%), and compare them to a case-control design with an Odds Ratio (OR) of 1.5, showing how a QT approach is superior to a traditional case-control. In the presented example, this method identifies putative susceptibility genes for schizophrenia which affect prefrontal efficiency and have functions related to cell migration, forebrain development and stress response. CONCLUSION: The use of QT as phenotypes provide increased statistical power over categorical association approaches and when combined with a GWAS creates a strategy for identification of unanticipated genes that modulate cognitive processes and cognitive disorders.
PMID: 19634037

Amin A
Department of Medicine, University of California-Irvine, 101 The City Drive, Orange, CA 92868, USA. anamin@uci.edu
Clinical and economic consequences of ventilator-associated pneumonia.
Clin Infect Dis. 2009 Aug 15;49 Suppl 1:S36-43
Increasing drug resistance rates among gram-negative pathogens that frequently cause ventilator-associated pneumonia have resulted in increased hospital mortality, longer hospital stays, and higher inpatient health care costs. There is an urgent need for effective therapies that lessen the clinical and economic consequences of this nosocomial infection. In a randomized, multicenter, prospective, phase 3 trial, medical resource use associated with doripenem was compared with that associated with imipenem for the treatment of ventilator-associated pneumonia. Analysis of medical resource use revealed that patients who received doripenem had a significantly shorter duration of hospital stay (22 vs. 27 days; P = .01)and duration of mechanical ventilation use (7 vs. 10 days; P = .03) than did patients who received imipenem. In addition, the duration of intensive care unit stay tended to be shorter for patients who received doripenem. The reduced medical resource use achieved with use of doripenem for treatment of ventilator-associated pneumonia may provide not only clinical benefits to patients but also economic benefits to hospitals and health care systems.
PMID: 19619020

Arce L,Pate KT,Waterman ML
Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA 92697-4025, USA. larce@coh.org
Groucho binds two conserved regions of LEF-1 for HDAC-dependent repression.
BMC Cancer. 2009;9:159
BACKGROUND: Drosophila Groucho and its human Transducin-like-Enhancer of Split orthologs (TLEs) function as transcription co-repressors within the context of Wnt signaling, a pathway with strong links to cancer. The current model for how Groucho/TLE's modify Wnt signaling is by direct competition with beta-catenin for LEF/TCF binding. The molecular events involved in this competitive interaction are not defined and the actions of Groucho/TLEs within the context of Wnt-linked cancer are unknown. METHODS: We used in vitro protein interaction assays with the LEF/TCF family member LEF-1, and in vivo assays with Wnt reporter plasmids to define Groucho/TLE interaction and repressor function. RESULTS: Mapping studies reveal that Groucho/TLE binds two regions in LEF-1. The primary site of recognition is a 20 amino acid region in the Context Dependent Regulatory domain. An auxiliary site is in the High Mobility Group DNA binding domain. Mutation of an eight amino acid sequence within the primary region (RFSHHMIP) results in a loss of Groucho action in a transient reporter assay. Drosophila Groucho, human TLE-1, and a truncated human TLE isoform Amino-enhancer-of-split (AES), work equivalently to repress LEF-1*beta-catenin transcription in transient reporter assays, and these actions are sensitive to the HDAC inhibitor Trichostatin A. A survey of Groucho/TLE action in a panel of six colon cancer cell lines with elevated beta-catenin shows that Groucho is not able to repress transcription in a subset of these cell lines. CONCLUSION: Our data shows that Groucho/TLE repression requires two sites of interaction in LEF-1 and that a central, conserved amino acid sequence within the primary region (F S/T/P/xx y I/L/V) is critical. Our data also reveals that AES opposes LEF-1 transcription activation and that both Groucho and AES repression require histone deacetylase activity suggesting multiple steps in Groucho competition with beta-catenin. The variable ability of Groucho/TLE to oppose Wnt signaling in colon cancer cells suggests there may be defects in one or more of these steps.
PMID: 19460168

Lin KK,Kumar V,Geyfman M,Chudova D,Ihler AT,Smyth P,Paus R,Takahashi JS,Andersen B
Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America.
Circadian clock genes contribute to the regulation of hair follicle cycling.
PLoS Genet. 2009 Jul;5(7):e1000573
Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.
PMID: 19629164

Butts CT
Department of Sociology and Institute for Mathematical Behavioral Sciences, University of California at Irvine, 3151 Social Science Plaza, Irvine, CA 92697-5100, USA. buttsc@uci.edu
Revisiting the foundations of network analysis.
Science. 2009 Jul 24;325(5939):414-6
Network analysis has emerged as a powerful way of studying phenomena as diverse as interpersonal interaction, connections among neurons, and the structure of the Internet. Appropriate use of network analysis depends, however, on choosing the right network representation for the problem at hand.
PMID: 19628855

Dean MN,Mull CG,Gorb SN,Summers AP
Ecology and Evolutionary Biology, University of California Irvine, Irvine CA, USA.
Ontogeny of the tessellated skeleton: insight from the skeletal growth of the round stingray Urobatis halleri.
J Anat. 2009 Jul 15;:
Abstract The majority of the skeleton of elasmobranch fishes (sharks, rays and relatives) is tessellated: uncalcified cartilage is overlain by a superficial rind of abutting, mineralized, hexagonal blocks called tesserae. We employed a diversity of imaging techniques on an ontogenetic series of jaw samples to investigate the development of the tessellated skeleton in a stingray (Urobatis halleri). We compared these data with the cellular changes that characterize cartilage calcification in bony skeletons. Skeletal growth is characterized by the appearance of tesserae as well as changes in chondrocyte shape, arrangement and density. Yolk sac embryos (35-56 mm disc width, DW) have untessellated lower jaw tissue wrapped in perichondrium and densely packed with chondrocytes. Chondrocyte density decreases dramatically after yolk sac absorption (histotroph stage: 57-80 mm DW) until the formation of tesserae, which are first visible using our techniques as thin (~60 microm), sub-perichondral plaques. During the histotroph stage, flattened chondrocytes align parallel to the perichondrium at the tissue periphery, where we believe they are incorporated into developing tesserae to form the cell-rich laminae observed within tesserae; in older animals peripheral cells in the uncalcified phase are rounder and less uniformly oriented. By parturition (~75 mm DW), cell density and the number of adjoining chondrocyte pairs (an indicator of cell division) have dropped to less than a third of their initial values; these remain low and tesserae continue to grow in size. The tessellated skeleton is a simple solution to the conundrum of growth in an endoskeleton with external mineralization and no remodeling. Although we see parallels with endochondral ossification (e.g. chondrocytes decreasing in density with age), the lack of chondrocyte hypertrophy and the fact that mineralization is sub-perichondral (not the case in mammalian cartilage) suggest that the similarities end there.
PMID: 19627389

Dasgupta G,Chentoufi AA,Nesburn AB,Wechsler SL,BenMohamed L
The Gavin S Herbert Eye Institute, Cellular and Molecular Immunology Laboratory, Department of Ophthalmology, University of California, Irvine, College of Medicine, Irvine, CA 92697-4375, USA. gdasgupt@uci.edu
New concepts in herpes simplex virus vaccine development: notes from the battlefield.
Expert Rev Vaccines. 2009 Aug;8(8):1023-35
The recent discovery that T cells recognize different sets of herpes simplex virus type 1 and type 2 epitopes from seropositive symptomatic and asymptomatic individuals might lead to a fundamental immunologic advance in vaccine development against herpes infection and diseases. The newly introduced needle-free mucosal (i.e., topical ocular and intravaginal) lipopeptide vaccines provide a novel strategy that might target ocular and genital herpes and possibly provide 'heterologous protection' from HIV-1. Indeed, mucosal self-adjuvanting lipopeptide vaccines are easy to manufacture, simple to characterize, extremely pure, cost-effective, highly immunogenic and safe. In this review, we bring together recent published and unpublished data that illuminates the status of epitope-based herpes vaccine development and present an overview of our recent approach to an 'asymptomatic epitope'-based lipopeptide vaccine.
PMID: 19627185

Keator DB
Brain Imaging Center, University of California - Irvine, Irvine, CA, USA.
Management of information in distributed biomedical collaboratories.
Methods Mol Biol. 2009;569:1-23
Organizing and annotating biomedical data in structured ways has gained much interest and focus in the last 30 years. Driven by decreases in digital storage costs and advances in genetics sequencing, imaging, electronic data collection, and microarray technologies, data is being collected at an alarming rate. The specialization of fields in biology and medicine demonstrates the need for somewhat different structures for storage and retrieval of data. For biologists, the need for structured information and integration across a number of domains drives development. For clinical researchers and hospitals, the need for a structured medical record accessible to, ideally, any medical practitioner who might require it during the course of research or patient treatment, patient confidentiality, and security are the driving developmental factors. Scientific data management systems generally consist of a few core services: a backend database system, a front-end graphical user interface, and an export/import mechanism or data interchange format to both get data into and out of the database and share data with collaborators. The chapter introduces some existing databases, distributed file systems, and interchange languages used within the biomedical research and clinical communities for scientific data management and exchange.
PMID: 19623483

Cerussi A,Siavoshi S,Durkin A,Chen C,Tanamai W,Hsiang D,Tromberg BJ
Laser Medical and Microbeam Program, Beckman Laser Institute, University of California, Irvine, 1110 Health Sciences Road, East, Irvine, California 92612, USA. acerussi@uci.edu
Effect of contact force on breast tissue optical property measurements using a broadband diffuse optical spectroscopy handheld probe.
Appl Opt. 2009 Jul 20;48(21):4270-7
We investigated the effects of operator-applied force on diffuse optical spectroscopy (DOS) by integrating a force transducer into the handheld probe. Over the typical range of contact forces measured in the breasts of eight patients, absorption and reduced scattering coefficients (650 to 1000 nm) variance was 3.1 +/- 1.0% and 1.0 +/- 0.4%. For trained operators, we observed <5% variation in hemoglobin and <2% variation in water and lipids. Contact force is not a significant source of variation, most likely because of a relatively wide probe surface area and the stability of the DOS method for calculating tissue optical properties.
PMID: 19623242

Lambros V
Department of Plastic Surgery, University of California-Irvine School of Medicine, Irvine, CA, USA. lambrosone@aol.com
Volumizing the brow with hyaluronic acid fillers.
Aesthet Surg J. 29(3):174-9
BACKGROUND: Aging eyes often are treated by excision of apparent excess skin and fat and, in some instances, by elevation of the brow. The result of these traditional approaches is increased definition of the orbit, which is not of benefit for all patients. In some cases, the addition of volume in the periorbital area may provide a better-looking result than traditional surgical alternatives. OBJECTIVE: The author describes the use of hyaluronic acid (HA) fillers for improvement of the periorbital region. METHODS: Using local anesthetic, patients are provided with a preview of the aesthetic result of treatment with HA fillers to add volume to the brow. Most treatments are performed using HA fillers, which have the benefit of results that are both reversible and long-lasting. The author uses a fanning technique to inject small quantities of material. RESULTS: The use of these techniques results in a high degree of patient satisfaction. Occasional minor irregularities may occur, but these can be smoothed out by massage or blended by further injection. Results lasting two years are common and we have observed longevity of three years or more in some patients. Some brow configurations that falsely project emotional states, such as anxiety, may also be corrected. CONCLUSIONS: As in other types of cosmetic surgery, patient selection is key. In properly selected patients, increased fullness of the upper lids is preferable to the greater definition of the lids resulting from traditional surgical techniques. The longevity of treatment and reversibility of changes to the upper lids with HA fillers render this approach both cost-effective and safe.
PMID: 19621494

Campbell DR
Department of Ecology & Evolutionary Biology, University of California, Irvine, 92697, USA. drcampbe@uci.edu
Using phenotypic manipulations to study multivariate selection of floral trait associations.
Ann Bot (Lond). 2009 Jun;103(9):1557-66
BACKGROUND: A basic theme in the study of plant-pollinator interactions is that pollinators select not just for single floral traits, but for associations of traits. Responses of pollinators to sets of traits are inherent in the idea of pollinator syndromes. In its most extreme form, selection on a suite of traits can take the form of correlational selection, in which a response to one trait depends on the value of another, thereby favouring floral integration. Despite the importance of selection for combinations of traits in the evolution of flowers, evidence is relatively sparse and relies mostly on observational approaches. SCOPE: Here, methods for measuring selection on multivariate suites of floral traits are presented, and the studies to date are reviewed. It is argued that phenotypic manipulations present a powerful, but rarely used, approach to teasing apart the separate and combined effects of particular traits. The approach is illustrated with data from studies of alpine plants in Colorado and New Zealand, and recommendations are made about several features of the design of such experiments. CONCLUSIONS: Phenotypic manipulations of two or more traits in combination provide a direct way of testing for selection of floral trait associations. Such experiments will be particularly valuable if rooted in hypotheses about differences between types of pollinators and tied to a proposed evolutionary history.
PMID: 19218579

Skeem J,Eno Louden J,Manchak S,Vidal S,Haddad E
Psychology & Social Behavior, 3311 Social Ecology II, University of California, Irvine, Irvine, CA, 92697-7085, USA. skeem@uci.edu
Social networks and social control of probationers with co-occurring mental and substance abuse problems.
Law Hum Behav. 2009 Apr;33(2):122-35
Probationers with co-occurring mental and substance abuse problems (PCPs) are both subject to considerable social control, and at high risk of probation failure. In this study, we screened 601 probationers for symptoms, interviewed 82 identified PCPs about their relationships, and then followed these PCPs for eight months to record treatment nonadherence and other probation violations. First, PCPs' social networks were small, heavily comprised of professionals and opposing forces who engaged in risky behavior, and saturated with pressure to adhere to treatment. Second, the size and composition of PCPs' social networks were more relevant to rule compliance than social support and undermining. Third, the quality of PCPs' relationships was key: satisfying relationships with clinicians and, to a lesser extent, officers and the core network related to low perceived coercion, high treatment adherence, and low risk of future violations. In particular, having a likable clinician who engaged in participatory decision-making reduced the risk of violations. Implications for contextually sensitive risk reduction efforts are discussed.
PMID: 18581220

Karamurzin Y,Rutgers JK
Department of Pathology and Laboratory Medicine, University of California Irvine, Orange, California, USA. ykaramur@uci.edu
DNA mismatch repair deficiency in endometrial carcinoma.
Int J Gynecol Pathol. 2009 May;28(3):239-55
Microsatellite instability (MSI) is the hallmark of a molecular pathway to carcinogenesis due to sporadic or inherited abnormalities of DNA mismatch repair genes. Inherited mutations are seen in hereditary nonpolyposis colorectal cancer syndrome. Endometrial carcinoma shows as high an incidence of MSI as does colorectal carcinoma. This review provides a framework for the gynecologic pathologist to understand the complexities of MSI in endometrial carcinoma, by discussing the basic mechanisms of mismatch repair and carcinogenesis, testing, the morphologic features of MSI endometrial cancer and the contradictory data regarding prognosis.
PMID: 19620942

Bagchi S,Falvo C,Mukamel S,Hochstrasser RM
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, and Department of Chemistry, University of California Irvine, Irvine, California 92697-2025.
2D-IR Experiments and Simulations of the Coupling between Amide-I and Ionizable Side Chains in Proteins: Application to the Villin Headpiece.
J Phys Chem B. 2009 Jul 20;:
The carboxylate side chains of Asp and Glu have significant coupling with the amide states of the backbone of the Villin headpiece. In two-dimensional spectroscopy, cross peaks are observed between these side chains and the main amide-I band. To model the absorption of the side chains, the electric field variations of vibrational frequencies of a carboxylic acid group (neutral form, CH(3)-COOH) and a carboxylate group (ionized form, CH(3)-COO(-)) are parametrized by means of density functional theory calculations. Simulations indicate that the side chains significantly couple to only one or two amide-I modes out of all of the amino acid residues which makes them useful as spectroscopic markers, providing information about the local structural behavior of the protein. Both experiment and simulations show that the cross peaks between the carboxylate and the amide-I bands are significantly diminished above the melting temperature.
PMID: 19618902

Kain ZN,MacLaren JE,Herrmann L,Mayes L,Rosenbaum A,Hata J,Lerman J
Department of Anesthesiology, University of California, Irvine School of Medicine, Irvine, California, USA. zkain@uci.edu
Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery.
Anesthesiology. 2009 Jul;111(1):44-9
BACKGROUND: Studies conducted in adults undergoing surgery reported a beneficial effect of oral melatonin administered before surgery. There is a paucity of such data in children undergoing anesthesia and surgery. METHODS: Children undergoing surgery were randomly assigned to receive preoperatively oral midazolam 0.5 mg/kg or oral melatonin 0.05 mg/kg, 0.2 mg/kg, or 0.4 mg/kg. The primary outcome of the study was preoperative anxiety (Yale Preoperative Anxiety Scale). The secondary outcomes were the children's compliance with induction (Induction Compliance Checklist), emergence behavior (Keegan scale), and parental anxiety (State-Trait Anxiety Inventory). RESULTS: Repeated measures ANOVA showed that children who received melatonin at any of the three doses were more anxious compared with children who received midazolam (P < 0.001). Parental anxiety did not differ on the basis of the experimental condition (P = ns). The melatonin groups showed a dose-response effect on emergence behavior. Children who received melatonin developed less emergence delirium compared with those who received midazolam (P < 0.05), and the effect was dose related; the incidence after 0.05 mg/kg melatonin was 25.0%, incidence after 0.2 mg/kg melatonin was 8.3%, and incidence after 0.4 mg/kg melatonin was 5.4%. CONCLUSIONS: Midazolam is more effective than melatonin in reducing children's anxiety at induction of anesthesia. Melatonin showed a direct dose-dependent effect on emergence delirium.
PMID: 19546692

Nageswaran JM,Dutt N,Krichmar JL,Nicolau A,Veidenbaum AV
Department of Computer Science, University of California Irvine, Irvine, CA 92697-3435, United States. jmoorkan@uci.edu
A configurable simulation environment for the efficient simulation of large-scale spiking neural networks on graphics processors.
Neural Netw. 22(5-6):791-800
Neural network simulators that take into account the spiking behavior of neurons are useful for studying brain mechanisms and for various neural engineering applications. Spiking Neural Network (SNN) simulators have been traditionally simulated on large-scale clusters, super-computers, or on dedicated hardware architectures. Alternatively, Compute Unified Device Architecture (CUDA) Graphics Processing Units (GPUs) can provide a low-cost, programmable, and high-performance computing platform for simulation of SNNs. In this paper we demonstrate an efficient, biologically realistic, large-scale SNN simulator that runs on a single GPU. The SNN model includes Izhikevich spiking neurons, detailed models of synaptic plasticity and variable axonal delay. We allow user-defined configuration of the GPU-SNN model by means of a high-level programming interface written in C++ but similar to the PyNN programming interface specification. PyNN is a common programming interface developed by the neuronal simulation community to allow a single script to run on various simulators. The GPU implementation (on NVIDIA GTX-280 with 1 GB of memory) is up to 26 times faster than a CPU version for the simulation of 100K neurons with 50 Million synaptic connections, firing at an average rate of 7 Hz. For simulation of 10 Million synaptic connections and 100K neurons, the GPU SNN model is only 1.5 times slower than real-time. Further, we present a collection of new techniques related to parallelism extraction, mapping of irregular communication, and network representation for effective simulation of SNNs on GPUs. The fidelity of the simulation results was validated on CPU simulations using firing rate, synaptic weight distribution, and inter-spike interval analysis. Our simulator is publicly available to the modeling community so that researchers will have easy access to large-scale SNN simulations.
PMID: 19615853

Bruckner TA,Saxton KB,Anderson E,Goldman S,Gould JB
Program in Public Health, University of California Irvine, Irvine, CA 92697, USA. tbruckne@uci.edu
From paradox to disparity: trends in neonatal death in very low birth weight non-Hispanic black and white infants, 1989-2004.
J Pediatr. 2009 Oct;155(4):482-7
OBJECTIVES: To examine temporal trends in race-specific neonatal death in California to determine whether the overall decline in mortality attenuated the paradoxical survival advantage of very low birth weight (VLBW; birth weight < 1500 g) non-Hispanic black infants relative to VLBW non-Hispanic white infants. STUDY DESIGN: The data set comprised the California birth cohort file on non-Hispanic black and non-Hispanic white VLBW neonatal mortality for 1989-2004. Logistic regression methods were used to control for potentially confounding maternal characteristics. RESULTS: In 1989 and 1990, non-Hispanic black VLBW infants demonstrated a paradox of lower neonatal mortality (adjusted odds ratio [aOR] = 0.84; 95% confidence interval [CI] = 0.75-0.94). This survival advantage disappeared after 1991, however. In 2003 and 2004, the incidence of neonatal mortality increased in non-Hispanic black VLBW infants but decreased in non-Hispanic white VLBW infants, resulting in a racial disparity (aOR = 1.34; 95% CI = 1.14-1.56). CONCLUSIONS: An initial survival paradox transformed into a disparity. The magnitude of this non-Hispanic black/non-Hispanic white VLBW disparity rose to its highest levels in the last 2 years of the study period. Moreover, the steady mortality increase in VLBW non-Hispanic black VLBW infants since 2001 reversed the secular decline in neonatal mortality in this population. Our findings underscore the need to augment strategies to improve the health trajectory of gestation in non-Hispanic black women.
PMID: 19615693

Romney AK,Chiao CC
Institute for Mathematical Behavioral Sciences, University of California, Irvine, CA 92697, USA. akromney@uci.edu
Functional computational model for optimal color coding.
Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10376-81
This paper presents a computational model for color coding that provides a functional explanation of how humans perceive colors in a homogeneous color space. Beginning with known properties of human cone photoreceptors, the model estimates the locations of the reflectance spectra of Munsell color chips in perceptual color space as represented in the CIE L*a*b* color system. The fit between the two structures is within the limits of expected measurement error. Estimates of the structure of perceptual color space for color anomalous dichromats missing one of the normal cone photoreceptors correspond closely to results from the Farnsworth-Munsell color test. An unanticipated outcome of the model provides a functional explanation of why additive lights are always red, green, and blue and provide maximum gamut for color monitors and color television even though they do not correspond to human cone absorption spectra.
PMID: 19497870

Fu J,Oveisi F,Gaetani S,Lin E,Piomelli D
Department of Psychiatry, University of California, Irvine, CA 92697-4625, USA. jinf@uci.edu
Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats.
Neuropharmacology. 2005 Jun;48(8):1147-53
The fatty-acid ethanolamide, oleoylethanolamide (OEA), is a naturally occurring lipid that regulates feeding and body weight [Rodriguez de Fonseca, F., Navarro, M., Gomez, R., Escuredo, L., Nava, F., Fu, J., Murillo-Rodriguez, E., Giuffrida, A., LoVerme, J., Gaetani, S., Kathuria, S., Gall, C., Piomelli, D., 2001. An anorexic lipid mediator regulated by feeding. Nature 414, 209-212], and serves as an endogenous agonist of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) [Fu, J., Gaetani, S., Oveisi, F., Lo Verme, J., Serrano, A., Rodriguez De Fonseca, F., Rosengarth., A., Luecke, H., Di Giacomo, B., Tarzia, G., Piomelli, D., 2003. Oleoylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425, 90-93], a ligand-activated transcription factor that regulates several aspects of lipid metabolism [. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. 20, 649-688]). OEA reduces food intake in wild-type mice, but not in mice deficient in PPAR-alpha (PPAR-alpha(-/-)), an effect that is also observed with the PPAR-alpha agonists Wy-14643 and GW7647 [Brown, P.J., Chapman, J.M., Oplinger, J.A., Stuart, L.W., Willson, T.M. and Wu, Z., 2000. Chemical compounds as selective activators of PPAR-alpha. PCT Int. Appl., 32; . The PPARs: from orphan receptors to drug discovery. J. Med. Chem. 43, 527-550]. By contrast, specific agonists of PPAR-delta/beta (GW501516) or PPAR-gamma (ciglitazone) have no such effect. In obese Zucker rats, which lack functional leptin receptors, OEA reduces food intake and lowers body-weight gain along with plasma lipid levels. Similar effects are seen in diet-induced obese rats and mice. In the present study, we report that subchronic OEA treatment (5mgkg(-1), intraperitoneally, i.p., once daily for two weeks) in Zucker rats initiates transcription of PPAR-alpha and other PPAR-alpha target genes, including fatty-acid translocase (FAT/CD36), liver fatty-acid binding protein (L-FABP), and uncoupling protein-2 (UCP-2). Moreover, OEA decreases neutral lipid content in hepatocytes, as assessed by Oil red O staining, as well as serum cholesterol and triglyceride levels. The results suggest that OEA regulates lipid metabolism and that this effect may contribute to its anti-obesity properties.
PMID: 15910890

Kain ZN,MacLaren JE,Hammell C,Novoa C,Fortier MA,Huszti H,Mayes L
Department of Anesthesiology and Perioperative Care, Pediatrics & Psychiatry, University of California, Irvine, CA, USA. zkain@uci.edu
Healthcare provider-child-parent communication in the preoperative surgical setting.
Paediatr Anaesth. 2009 Apr;19(4):376-84
OBJECTIVES: Although preoperative preparation programs were once common, most children currently undergoing outpatient surgery are first exposed to the hospital on the day of the procedure. It is advocated that these outpatient children undergo the preparation just prior to surgery. AIM: To assess the amount of time that healthcare providers spend with children and families on the day of surgery in the preoperative area. MATERIALS AND METHODS: The study used video infrastructure in the preoperative holding area of Yale New Haven Children's Hospital to record all interactions between children, families, and healthcare providers. Videotapes were coded to characterize and quantify behaviors of healthcare professionals. RESULTS: On the day of surgery, healthcare providers spent medians of 2.75-4.81 min interacting with children and parents in the preoperative area. Families spent a median of 46.5 min in the preoperative area. Healthcare professionals spent the most time in medical talk (averages of 42.5-48.2% of time spent with family) and little time was spent in nonmedical talk (range of 6.2-6.9% of time spent with family). Anesthesiologists and surgeons spent 28% and 18% of the interview in talk to children; admitting nurses spent more of the interview talking to children (43%). CONCLUSIONS: Families interact with healthcare providers for only a small proportion of the time they spent in the preoperative area. This is likely to be a result of increased production pressure in the perioperative settings and has implications for providing preparation for surgery on the morning of the procedure.
PMID: 19187045

Bae HK,Olson BH,Hsu KL,Sorooshian S
Henry Samueli School of Engineering, Department of Civil and Environmental Engineering, University of California, Irvine, CA 92697, USA. baeh@uci.edu
Identification and application of physical and chemical parameters to predict indicator bacterial concentration in a small Californian creek.
Water Environ Res. 2009 Jun;81(6):633-40
This study of Aliso Creek in California aimed to identify physical and chemical parameters that could be measured instantly to be used in a model to serve as surrogates for indicator bacterial concentrations during dry season flow. In this study, a new data smoothing technique and ranking/categorizing analysis was used to reduce variation to allow better delineation of the relationships between adopted variables and concentrations of indicator bacteria. The ranking/categorizing approach clarified overall trends between physico-chemical data and the indicators and suggested sources of the bacteria. This study also applied a principle component regression model to the data. Although the model was promising for predicting concentrations of total and fecal coliforms, it was somewhat weaker in predicting enteroccocci.
PMID: 19601429


 
 
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