Dwyer JB,McQuown SC,Leslie FM
Department of Pharmacology, Med Surge II, School of Medicine, University of California, Irvine, CA 92697, USA. jbdwyer@uci.edu
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The dynamic effects of nicotine on the developing brain.
Pharmacol Ther. 2009 May;122(2):125-39
Nicotinic acetylcholine receptors (nAChRs) regulate critical aspects of brain maturation during the prenatal, early postnatal, and adolescent periods. During these developmental windows, nAChRs are often transiently upregulated or change subunit composition in those neural structures that are undergoing major phases of differentiation and synaptogenesis, and are sensitive to environmental stimuli. Nicotine exposure, most often via tobacco smoke, but increasingly via nicotine replacement therapy, has been shown to have unique effects on the developing human brain. Consistent with a dynamic developmental role for acetylcholine, exogenous nicotine produces effects that are unique to the period of exposure and that impact the developing structures regulated by acetylcholine at that time. Here we present a review of the evidence, available from both the clinical literature and preclinical animal models, which suggests that the diverse effects of nicotine exposure are best evaluated in the context of regional and temporal expression patterns of nAChRs during sensitive maturational periods, and disruption of the normal developmental influences of acetylcholine. We present evidence that nicotine interferes with catecholamine and brainstem autonomic nuclei development during the prenatal period of the rodent (equivalent to first and second trimester of the human), alters the neocortex, hippocampus, and cerebellum during the early postnatal period (third trimester of the human), and influences limbic system and late monoamine maturation during adolescence.
PMID: 19268688
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Ayers FR,Cuccia DJ,Kelly KM,Durkin AJ
University of California-Irvine, Beckman Laser Institute, Irvine, California 92612, USA. fayers@uci.edu
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Wide-field spatial mapping of in vivo tattoo skin optical properties using modulated imaging.
Lasers Surg Med. 2009 Aug;41(6):442-53
BACKGROUND AND OBJECTIVES: Modulated imaging is a new modality capable of wide-field, spatially resolved measurement of in vivo optical properties. Based on spatial light modulation, the method is inexpensive, non-contact, and allows spatial mapping of tissue absorption and reduced scattering coefficients at any wavelength between 450 and 1,100 nm. Currently, clinicians rely on qualitative visual inspection to guide parameter selection for laser-based tattoo removal. MI provides quantitative measurements of multi-colored tattooed skin which may help guide treatment and objectively assess response. STUDY DESIGN/MATERIALS AND METHODS: We have measured the spatially varying optical properties of multi-colored tattooed skin over a 50 mm x 50 mm field of view at wavelengths ranging from 650 to 970 nm using MI. These measurements were compared to a similar field of view of non-tattooed skin from an adjacent area. RESULTS: We have determined the differentiated optical properties in vivo of multi-colored tattooed skin versus non-tattooed skin. CONCLUSIONS: MI provides spatially resolved quantitative information with potential for quantitative assessment of response to treatment and may provide guidance for laser tattoo removal in the future.
PMID: 19588528
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Metz M
Department of ORLIHNS, University of California-Irvine.
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Ethics for Speech-Language Pathologists and Audiologists: An Illustrative Casebook.
Int J Audiol. 2009 Jul 8;:1
PMID: 19588277
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Cooke J,Sullivan M,Barton EJ,Bullock JS,Carlberg RG,Gal-Yam A,Tollerud E
Center for Cosmology, Department of Physics and Astronomy, University of California, Irvine, California 92697-4574, USA. cooke@uci.edu
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Type IIn supernovae at redshift z approximately 2 from archival data.
Nature. 2009 Jul 9;460(7252):237-9
Supernovae have been confirmed to redshift z approximately 1.7 (refs 1, 2) for type Ia (thermonuclear detonation of a white dwarf) and to z approximately 0.7 (refs 1, 3-5) for type II (collapse of the core of the star). The subclass type IIn (ref. 6) supernovae are luminous core-collapse explosions of massive stars and, unlike other types, are very bright in the ultraviolet, which should enable them to be found optically at redshifts z approximately 2 and higher. In addition, the interaction of the ejecta with circumstellar material creates strong, long-lived emission lines that allow spectroscopic confirmation of many events of this type at z approximately 2 for 3-5 years after explosion (ref. 14). Here we report three spectroscopically confirmed type IIn supernovae, at redshifts z = 0.808, 2.013 and 2.357, detected in archival data using a method designed to exploit these properties at z approximately 2. Type IIn supernovae directly probe the formation of massive stars at high redshift. The number found to date is consistent with the expectations of a locally measured stellar initial mass function, but not with an evolving initial mass function proposed to explain independent observations at low and high redshift.
PMID: 19587765
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Meyskens FL
Chao Family Comprehensive Cancer Center and Department of Medicine, University of California Irvine, Irvine, California, USA. flmeyske@uci.edu
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Food extracts for chemoprevention: quo vadis?
Cancer Prev Res (Phila Pa). 2009 Jul;2(7):608-10
PMID: 19584073
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Kuppermann BD
Retina Service, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, California 92697, USA. bdkupper@uci.edu
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Drug delivery strategies for combination ophthalmic treatments.
Retina. 2009 Jun;29(6 Suppl):S24-6
The most significant obstacle to the combination of drug therapies in age-related macular degeneration (AMD) may be drug delivery. Although the posterior of the eye can be reached by intravitreal injections and implants, AMD is a chronic disease process that is likely to require prolonged or indefinite exposure to antiproliferative agents. In addition to the difficulty of repeat dosing in the vitreal space, ocular anatomy prohibits substantial drug volumes, a limitation further compounded when combining two or more agents. With low penetration to target areas of AMD, pathophysiology, and risk of significant systemic toxicity through systemic drug delivery, innovative strategies for introducing agents to their site of action may be the critical component of improved outcomes.
PMID: 19553793
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Shin HW,Umber BJ,Meinardi S,Leu SY,Zaldivar F,Blake DR,Cooper DM
Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA. hyewons@uci.edu
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Acetaldehyde and hexanaldehyde from cultured white cells.
J Transl Med. 2009;7:31
BACKGROUND: Noninvasive detection of innate immune function such as the accumulation of neutrophils remains a challenge in many areas of clinical medicine. We hypothesized that granulocytes could generate volatile organic compounds. METHODS: To begin to test this, we developed a bioreactor and analytical GC-MS system to accurately identify and quantify gases in trace concentrations (parts per billion) emitted solely from cell/media culture. A human promyelocytic leukemia cell line, HL60, frequently used to assess neutrophil function, was grown in serum-free medium. RESULTS: HL60 cells released acetaldehyde and hexanaldehyde in a time-dependent manner. The mean +/- SD concentration of acetaldehyde in the headspace above the cultured cells following 4-, 24- and 48-h incubation was 157 +/- 13 ppbv, 490 +/- 99 ppbv, 698 +/- 87 ppbv. For hexanaldehyde these values were 1 +/- 0.3 ppbv, 8 +/- 2 ppbv, and 11 +/- 2 ppbv. In addition, our experimental system permitted us to identify confounding trace gas contaminants such as styrene. CONCLUSION: This study demonstrates that human immune cells known to mimic the function of innate immune cells, like neutrophils, produce volatile gases that can be measured in vitro in trace amounts.
PMID: 19402909
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Constantinescu CC,Mukherjee J
Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA. constant@uci.edu
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Performance evaluation of an Inveon PET preclinical scanner.
Phys Med Biol. 2009 May 7;54(9):2885-99
We evaluated the performance of an Inveon preclinical PET scanner (Siemens Medical Solutions), the latest MicroPET system. Spatial resolution was measured with a glass capillary tube (0.26 mm inside diameter, 0.29 mm wall thickness) filled with (18)F solution. Transaxial and axial resolutions were measured with the source placed parallel and perpendicular to the axis of the scanner. The sensitivity of the scanner was measured with a (22)Na point source, placed on the animal bed and positioned at different offsets from the center of the field of view (FOV), as well as at different energy and coincidence windows. The noise equivalent count rates (NECR) and the system scatter fraction were measured using rat-like (Phi = 60, L = 150 mm) and mouse-like (Phi = 25 mm, L = 70 mm) cylindrical phantoms. Line sources filled with high activity (18)F (>250 MBq) were inserted parallel to the axes of the phantoms (13.5 and 10 mm offset). For each phantom, list-mode data were collected over 24 h at 350-650 keV and 250-750 keV energy windows and 3.4 ns coincidence window. System scatter fraction was measured when the random event rates were below 1%. Performance phantoms consisting of cylinders with hot rod inserts filled with (18)F were imaged. In addition, we performed imaging studies that show the suitability of the Inveon scanner for imaging small structures such as those in mice with a variety of tracers. The radial, tangential and axial resolutions at the center of FOV were 1.46 mm, 1.49 and 1.15 mm, respectively. At a radial offset of 2 cm, the FWHM values were 1.73, 2.20 and 1.47 mm, respectively. At a coincidence window of 3.4 ns, the sensitivity was 5.75% for EW = 350-650 keV and 7.4% for EW = 250-750 keV. For an energy window of 350-650 keV, the peak NECR was 538 kcps at 131.4 MBq for the rat-like phantom, and 1734 kcps at 147.4 MBq for the mouse-like phantom. The system scatter fraction values were 0.22 for the rat phantom and 0.06 for the mouse phantom. The Inveon system presents high image resolution, low scatter fraction values and improved sensitivity and count rate performance.
PMID: 19384008
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Elmore E,Lao XY,Kapadia R,Redpath JL
Department of Radiation Oncology and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California 92967, USA.
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Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.
Radiat Res. 2009 Jun;171(6):764-70
Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.
PMID: 19580483
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Fu LW,Longhurst JC
Department of Medicine, University of California, Irvine, CA 92697, USA. lwfu@uci.edu
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Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors.
J Appl Physiol. 2009 Jun;106(6):1800-9
Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (vlPAG), and rostral ventrolateral medulla (rVLM). Neurons in the ARC provide excitatory input to the vlPAG, whereas the vlPAG inhibits neuronal activity in the rVLM. gamma-Aminobutyric acid (GABA) and glutamate (Glu) have been identified in the vlPAG. Endocannabinoids (ECs), acting as atypical neurotransmitters, inhibit the release of both neurotransmitters in the hypothalamus and midbrain through a presynaptic cannabinoid type 1 (CB(1)) receptor mechanism. The EC system has been observed in the dorsal but not in the vlPAG. Since it is uncertain whether ECs influence GABA and Glu in the vlPAG, the present study tested the hypothesis that EA modulates the release of these neurotransmitters in the vlPAG through a presynaptic CB(1) receptor mechanism. We measured the release of GABA and Glu simultaneously by using HPLC to assess samples collected with microdialysis probes inserted unilaterally into the vlPAG of intact anesthetized rats. Twenty-eight min of EA (2 Hz, 2-4 mA, 0.5 ms) at the P5-6 acupoints reduced the release of GABA by 39% during EA and by 44% 15 min after EA. Thirty-five minutes after EA, GABA concentrations returned to pre-EA levels. In contrast, sham EA did not change the vlPAG GABA concentration. Blockade of CB(1) receptors with AM251, a selective CB(1) receptor antagonist, reversed the EA-modulated changes in GABA concentration, whereas microinjection of vehicle into the vlPAG did not alter EA-modulated GABA changes. In addition, we observed no changes in the vlPAG Glu concentrations during EA, although the baseline concentration of Glu was much higher than that of GABA (3,541 +/- 373 vs. 33.8 +/- 8.7 nM, Glu vs. GABA). These results suggest that EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA, but not Glu, in the vlPAG, most likely through a presynaptic CB(1) receptor mechanism.
PMID: 19359606
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Tjen-A-Looi SC,Li P,Longhurst JC
School of Medicine, University of California, Irvine, CA 92697-4075, USA. stjenalo@uci.edu
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Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA.
J Appl Physiol. 2009 Jun;106(6):1793-9
A long-loop pathway, involving the hypothalamic arcuate nucleus (ARC), ventrolateral periaqueductal gray (vlPAG), and the rostral ventrolateral medulla (rVLM), is essential in electroacupuncture (EA) attenuation of sympathoexcitatory cardiovascular reflex responses. The ARC provides excitatory input to the vlPAG, which, in turn, inhibits neuronal activity in the rVLM. Although previous studies have shown that endocannabinoid CB(1) receptor activation modulates gamma-aminobutyric acid (GABA)-ergic and glutamatergic neurotransmission in the dorsolateral PAG in stress-induced analgesia, an important role for endocannabinoids in the vlPAG has not yet been observed. We recently have shown (Fu LW, Longhurst JC. J Appl Physiol; doi:10.1152/japplphysiol.91648.2008) that EA reduces the local vlPAG concentration of GABA, but not glutamate, as measured with high-performance liquid chromatography from extracellular samples collected by microdialysis. We, therefore, hypothesized that, during EA, endocannabinoids, acting through CB(1) receptors, presynaptically inhibit GABA release to disinhibit the vlPAG and ultimately modulate excitatory reflex blood pressure responses. Rats were anesthetized, ventilated, and instrumented to measure heart rate and blood pressure. Gastric distention-induced blood pressure responses of 18 +/- 5 mmHg were reduced to 6 +/- 1 mmHg by 30 min of low-current, low-frequency EA applied bilaterally at pericardial P 5-6 acupoints overlying the median nerves. Like EA, microinjection of the fatty acid amide hydrolase inhibitor URB597 (0.1 nmol, 50 nl) into the vlPAG to increase endocannabinoids locally reduced the gastric distention cardiovascular reflex response from 21 +/- 5 to 3 +/- 4 mmHg. This inhibition was reversed by pretreatment with the GABA(A) antagonist gabazine (27 mM, 50 nl), suggesting that endocannabinoids exert their action through a GABAergic receptor mechanism in the vlPAG. The EA-related inhibition from 18 +/- 3 to 8 +/- 2 mmHg was reversed to 14 +/- 2 mmHg by microinjection of the CB(1) receptor antagonist AM251 (2 nmol, 50 nl) into the vlPAG. Pretreatment with gabazine eliminated reversal following CB(1)-receptor blockade. Thus EA releases endocannabinoids and activates presynaptic CB(1) receptors to inhibit GABA release in the vlPAG. Reduction of GABA release disinhibits vlPAG cells, which, in turn, modulate the activity of rVLM neurons to attenuate the sympathoexcitatory reflex responses.
PMID: 19325030
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Vardo-Zalik AM,Ford AF,Schall JJ
University of California at Irvine, 92697, USA. avardoza@uci.edu
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Detecting number of clones, and their relative abundance, of a malaria parasite (Plasmodium mexicanum) infecting its vertebrate host.
Parasitol Res. 2009 Jul;105(1):209-15
Microsatellites, short tandem repeats of nucleotides in the genome, are useful markers to detect clonal diversity within Plasmodium infections. However, accuracy in determining number of clones and their relative proportions based on standard genetic analyzer instruments is poorly known. DNA extracted from lizards infected with a malaria parasite, Plasmodium mexicanum, provided template to genotype the parasite based on three microsatellite markers. Replicate genotyping of the same natural infections demonstrated strong repeatability of data from the instrument. Mixing DNA extracted from several infected lizards simulated mixed-clone infections with known clonal diversity and relative proportions of clones (N = 56 simulations). The instrument readily detected at least four alleles (clones), even when DNA concentrations among clones differed up to tenfold, but alleles of similar size can be missed because they fall within the "stutter" artifact, and rarely does an allele fail to be detected. For simulations of infections that changed their relative proportions over time, changes in relative peak heights on the instrument output closely followed the known changes in relative proportions. Such data are useful for a broad range of studies on the ecology of malaria parasites.
PMID: 19277713
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Choi B,Bjorner JB,Ostergren PO,Clays E,Houtman I,Punnett L,Rosengren A,De Bacquer D,Ferrario M,Bilau M,Karasek R
Center for Occupational and Environmental Health, University of California Irvine, Irvine, CA 92617, USA. b.choi@uci.edu
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Cross-language differential item functioning of the job content questionnaire among European countries: the JACE study.
Int J Behav Med. 2009;16(2):136-47
BACKGROUND: Little is known about cross-language measurement equivalence of the job content questionnaire (JCQ) PURPOSE: The purposes of this study were to assess the extent of cross-language differential item functioning (DIF) of the 27 JCQ items in six languages (French, Dutch, Belgian-French, Belgian-Dutch (Flemish), Italian, and Swedish) from six European research centers and to test whether its effects on the scale-level mean comparisons among the centers were substantial or not. METHOD: A partial gamma coefficient method was used for statistical DIF analyses where the Flemish JCQ was the reference for other language versions. Additionally, equivalence between the Flemish and Dutch translations was subjected to a judgmental review. RESULTS: On average, 36% to 39% of the total tested items appeared to be cross-language DIF items in the statistical analyses. The judgmental review indicated that half of the DIF items may be associated with translation difference. The impacts of the DIF items on the mean comparisons of the JCQ scales between the centers were non-trivial: underestimated skill discretion (Milan), underestimated decision authority (Leiden), underestimated psychological demands (Milan women), and incomparable coworker support (Gothenburg 95). CONCLUSION: Cross-language DIF of the JCQ among European countries should be considered in international comparative studies on psychosocial job hazards using JCQ scales.
PMID: 19575297
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Bailey SR
University of California, Department of Sociology, 3151 Social Science Plaza, Irvine, California 92697-5100, USA. bailey@uci.edu
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Unmixing for race making in Brazil.
AJS. 2008 Nov;114(3):577-614
This article analyzes race-targeted policy in Brazil as both a political stake and a powerful instrument in an unfolding classificatory struggle over the definition of racial boundaries. The Brazilian state traditionally embraced mixed-race classification, but is adopting racial quotas employing a black/white scheme. To explore potential consequences of that turn for beneficiary identification and boundary formation, the author analyzes attitudinal survey data on race-targeted policy and racial classification in multiple formats, including classification in comparison to photographs. The results show that almost half of the mixed-race sample, when constrained to dichotomous classification, opts for whiteness, a majority rejects mixed-race individuals for quotas, and the mention of quotas for blacks in a split-ballot experiment nearly doubles the percentage choosing that racial category. Theories of how states make race emphasize the use of official categories to legislate exclusion. In contrast, analysis of the Brazilian case illuminates how states may also make race through policies of official inclusion.
PMID: 19569393
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Feliciano C,Robnett B,Komaie G
Department of Sociology, University of California, Irvine, CA 92697-5100, USA. felician@uci.edu
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Gendered racial exclusion among White internet daters.
Soc Sci Res. 2009 Mar;38(1):39-54
Acceptance by the dominant group reveals the current standing of racial groups in the U.S. hierarchy, as well as the possibility for assimilation. However, few researchers have addressed the gendered nature of racial preferences by whites. We examine whites' exclusion of blacks, Latinos, Asians, Middle Easterners, East Indians and Native Americans as possible dates, using a sample of profiles collected from an internet dating website. We find that white men are more willing than white women to date non-whites in general, yet, with the exception of their top two preferences for dates, whites and Latinos, the racial hierarchies of males and females differ. Among daters with stated racial preferences, white men are more likely to exclude blacks as possible dates, while white women are more likely to exclude Asians. We argue that exclusion relates to racialized images of masculinity and femininity, and shapes dating and marriage outcomes, and thus minority groups' possibilities for full social incorporation.
PMID: 19569291
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Burke MK,Rose MR
Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92617-2525, USA. burkem@uci.edu
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Experimental evolution with Drosophila.
Am J Physiol Regul Integr Comp Physiol. 2009 Jun;296(6):R1847-54
Experimental evolution is a powerful approach that can be used for the study of adaptation. Evolutionary biologists often use Drosophila as a model organism in experiments that test theories about the evolution of traits related to fitness. Such evolution experiments can take three forms: direct selection for a trait of interest; surveys of traits of interest in populations selected for other traits; and reverse selection. We review some of the Drosophila experiments that have provided insight into both the evolution of particular physiological traits and the correlations between physiological and life history traits, focusing on stress resistance. The most common artifacts that can obscure the results from evolution experiments are discussed. We also include a treatment of genomic technologies that are now available for the Drosophila model. The primary goal of this review is to introduce the kind of experimental evolution strategies and technologies that evolutionary physiologists might use in the future.
PMID: 19339679
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Suding KN,Hobbs RJ
Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, Irvine, CA 92697-2525, USA. ksuding@uci.edu
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Threshold models in restoration and conservation: a developing framework.
Trends Ecol Evol. 2009 May;24(5):271-9
The recognition that a system can appear resilient to changes in the environment, only to reach a critical threshold of rapid and unexpected change, is spurring work to apply threshold models in conservation and restoration. Here we address the relevance of threshold models to habitat management. Work to date indicates these concepts are highly applicable: human impacts can widen the range of habitats where threshold dynamics occur and shift communities into new states that are difficult to reverse. However, in many applied settings, threshold concepts are being adopted without evaluation of evidence and uncertainty. We suggest a framework for incorporating threshold models that reflects an emphasis on applicability to decision making and management on relatively short timescales and in human-impacted systems.
PMID: 19269057
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Vilberg KL,Rugg MD
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA 92697-3800, USA. kvilberg@uci.edu
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Functional significance of retrieval-related activity in lateral parietal cortex: Evidence from fMRI and ERPs.
Hum Brain Mapp. 2009 May;30(5):1490-501
The present study addressed the question whether neural activity in left lateral parietal cortex is modulated by amount of information recollected. In two experiments (one using fMRI and the other ERPs), subjects first studied pairs of pictures presented for either 1 or 6 s. They then performed a standard "Remember/Know" recognition memory test in which the old items comprised one of the pictures from each studied pair. In both experiments, a surprise posttest indicated that subjects recollected more details about the study presentation of the items presented for the longer duration. In the fMRI experiment, recollection- and familiarity-based recognition elicited activity in distinct cortical networks. Additionally, recollection-related activity in left inferior parietal cortex was of greater magnitude for test items presented for 6 s than for 1 s. In the ERP study the "left-parietal old/new effect"-a putative correlate of successful recollection-was likewise modulated by amount of information retrieved. Together, these findings provide further support for dual-process models of recognition memory and add weight to the proposal that retrieval-related activity in left inferior parietal cortex reflects processes supporting the online representation of retrieved episodic information.
PMID: 18649352
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Milne RL,Benítez J,Nevanlinna H,Heikkinen T,Aittomäki K,Blomqvist C,Arias JI,Zamora MP,Burwinkel B,Bartram CR,Meindl A,Schmutzler RK,Cox A,Brock I,Elliott G,Reed MW,Southey MC,Smith L,Spurdle AB,Hopper JL,Couch FJ,Olson JE,Wang X,Frederi
Affiliations of authors: Genetic and Molecular Epidemiology Group (RLM) and Human Genetics Group (JBe), Spanish National Cancer Research Centre [CNIO], Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras [CIBERER], Madrid, Spain (JBe); Department of Obstetrics and Gynecology (HN, TH), Department of Clinical Genetics (KA), and Department of Oncology (CB), Helsinki University Central Hospital, Helsinki, Finland; Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain (JIA); Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain (MPZ); Department of Obstetrics and Gynecology (BB) and Institute of Human Genetics (CRB), University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group (BB) and Division of Cancer Epidemiology (JC-C), German Cancer Research Center [DKFZ]), Heidelberg, Germany; Department of Gynaecology and Obstetrics, Technical University of Munich, Munich, Germany (AMe); Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, Köln, Germany (RKS); Institute for Cancer Studies (AC, IB, GE) and Academic Unit of Surgical Oncology (MWRR), Sheffield University Medical School, Sheffield, UK; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology (JLH, DRE) and Department of Pathology (MCS, LS), University of Melbourne, Victoria, Australia; Department of Laboratory Medicine and Pathology (FJC, XW) and Department of Health Sciences Research (JEO, ZF), Mayo Clinic, Rochester, MN; Department of Obstetrics and Gynaecology (TD, PS, PHi, NVB, MBe) and Department of Radiation Oncology (MBr, NVB), Hannover Medical School, Hannover, Germany; Department of Human Genetics (PD), Department of Pathology (PD), Department of Clinical Genetics (CJvA), and Department of Surgery (RAEMT), Leiden University Medical Centre, Leiden, the Netherlands; Department of Medical Oncology, Rotterdam Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands (CS); Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden (PHa, KC); Human Genetics Laboratory, Genome Institute of Singapore, Singapore (JLi, YL); Department of Oncology (SA, AMD, MM, PDPP), Department of Public Health and Primary Care (PDPP), University of Cambridge, Cambridge, UK; Division of Genetics and Population Health (GC-T, JBee, ABS), Queensland Institute of Medical Research (AOCS), Brisbane, Australia; Peter MacCallum Cancer Center, Melbourne, Australia (kConFab, AOCS); N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (NVB, NNA, IVZ); Department of Epidemiology, University of California Irvine, Irvine, CA (HA-C, AZ); Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (HB, CJ); University of Tübingen, Tübingen, Germany (HB, CJ); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (Y-DK); Institute of Pathology, University of Bonn, Bonn, Germany (SHa); University Breast Center (PAF, RS, MWB) and Institute of Human Genetics (ABE), University Hospital Erlangen, Erlangen, Germany; Department of Gynecology and Obstetrics, David Geffen School of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA (PAF); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia (GGG, GS, LB); Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK (OF, NJ); Cancer Research UK Epidemiology and Genetics Group, London School of Hygiene and Tropical Medicine, London, UK (OF, IdSS, JP); Section of Cancer Genetics (CT, SHi, AR, NR), Institute of Cancer Research (JP), Sutton, Surrey, UK; Department of Clinical Biochemistry and Department of Breast Surgery, Herlev University Hospital, University of Copenhagen, Denmark (BGN, SEB, HF); Seoul National University College of Medicine, Seoul, Korea (DK, K-YY, D-YN); Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio (AMa, V-MK); Department of Oncology and Department of Pathology, University Hospital of Kuopio and Biocenter Kuopio, Kuopio, Finland (VK); Department of Oncology, Vaasa Central Hospital, Vaasa, Finland (VK); Division of Cancer Epidemiology and Genetics (MG-C, SC) and Hormonal and Reproductive Epidemiology Branch (LAB), National Cancer Institute, Rockville, MD; Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland (JLis); Department of Gynecology and Obstetrics, Ulm Medical School, Ulm, Germany (SW-G); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (C-YS, H-CW); Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan (J-CY); Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan (S-TC); Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia (MBe, EK); Department of Medical Genetics, Yakut Research Center of Russian Academy of Medical Sciences, Yakutsk, Russia (TN); Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK (MKH, JM, RP, DFE).
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Risk of Estrogen Receptor-Positive and -Negative Breast Cancer and Single-Nucleotide Polymorphism 2q35-rs13387042.
J Natl Cancer Inst. 2009 Jun 30;:
Background A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. Methods 2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided. Results We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P >/= .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002). Conclusion The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
PMID: 19567422
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Wang TH,Kruggel F,Rugg MD
Center for the Neurobiology of Learning and Memory, and Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-3800, United States. tracy.wang@uci.edu
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Effects of advanced aging on the neural correlates of successful recognition memory.
Neuropsychologia. 2009 Apr;47(5):1352-61
Functional neuroimaging studies have reported that the neural correlates of retrieval success (old>new effects) are larger and more widespread in older than in young adults. In the present study we investigated whether this pattern of age-related 'over-recruitment' continues into advanced age. Using functional magnetic resonance imaging (fMRI), retrieval-related activity from two groups (N=18 per group) of older adults aged 84-96 years ('old-old') and 64-77 years ('young-old') was contrasted. Subjects studied a series of pictures, half of which were presented once, and half twice. At test, subjects indicated whether each presented picture was old or new. Recognition performance of the old-old subjects for twice-studied items was equivalent to that of the young-old subjects for once-studied items. Old>new effects common to the two groups were identified in several cortical regions, including medial and lateral parietal and prefrontal cortex. There were no regions where these effects were of greater magnitude in the old-old group, and thus no evidence of over-recruitment in this group relative to the young-old individuals. In one region of medial parietal cortex, effects were greater (and only significant) in the young-old group. The failure to find evidence of over-recruitment in the old-old subjects relative to the young-old group, despite their markedly poorer cognitive performance, suggests that age-related over-recruitment effects plateau in advanced age. The findings for the medial parietal cortex underscore the sensitivity of this cortical region to increasing age.
PMID: 19428399
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Pyles JA,Grossman ED
Center for Cognitive Neuroscience & Department of Cognitive Sciences, University of California, Irvine, California 92697-5100, United States. jpyles@uci.edu
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Neural adaptation for novel objects during dynamic articulation.
Neuropsychologia. 2009 Apr;47(5):1261-8
Human observers readily identify objects with moving parts, and recognize their underlying structure even when the component parts undergo complex movement. This suggests the existence of neural representations that are invariant to motion and state of articulation, which together allow our visual system to maintain 'object constancy'. Ventral temporal cortex has previously been implicated in object perception and in coding object identity, but it is unclear where this is achieved when objects undergo motion-driven shape changes. In the present study, we use fMRI adaptation to probe the neural response properties when subjects view dynamic novel objects. Our results reveal neural selectivity for novel objects in the LOC region of the occipito-temporal lobe, even when those objects are viewed as moving and articulating. We also identify a bilateral area of posterior fusiform outside of the LOC with neural populations invariant to changes in the articulatory state of an object, a critical feature of object constancy. These results demonstrate the functional importance of ventral temporal cortex in the perception of moving objects, and the existence of neural populations coding for object constancy across movement and articulation.
PMID: 19428389
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Wilson SE,O'Riordan W,Hopkins A,Friedland HD,Barriere SL,Kitt MM,
Department of Surgery, University of California, Irvine School of Medicine, Orange, CA, USA. wilsonse@uci.edu
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Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections associated with surgical procedures.
Am J Surg. 2009 Jun;197(6):791-6
BACKGROUND: We compared telavancin with vancomycin for the treatment of complicated skin and skin-structure infections (cSSSI) caused by Gram-positive bacteria. METHODS: This was a retrospective analysis of clinical and microbiologic efficacy assessed at test-of-cure (7 to 14 days after completing therapy) in 194 patients from 2 randomized, double-blind clinical trials comparing telavancin (10 mg/kg intravenous [IV] every 24 hours; n = 101) with vancomycin (1 g IV every 12 hours; n = 93) for the treatment of cSSSI. RESULTS: Baseline characteristics were similar for both treatment groups. Clinical cure and microbiologic eradication rates demonstrated consistent trends favoring telavancin over vancomycin; however, the differences were not statistically significant. The incidence of adverse events was mostly similar between groups. CONCLUSIONS: The efficacy of telavancin was at least equivalent to that of vancomycin for the treatment of cSSSI. These data suggest that telavancin may be a useful alternative for treatment of cSSSI caused by S. aureus, particularly MRSA.
PMID: 19095213
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Kosins AM,McConnell MP,Mendoza C,Shepard B,Scholz T,Evans GR,Keirstead HS
Department of Tissue Engineering and Regenerative Medicine, Reeve-Irvine Research Center, Aesthetic and Plastic Surgery Institute, University of California, Irvine, Calif 92868, USA. akosins@uci.edu
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A novel model to measure the regenerative potential of the peripheral nervous system after experimental immunological demyelination.
Plast Reconstr Surg. 2009 Jun;123(6):1688-96
BACKGROUND: Immunological demyelination is a proposed strategy to improve nerve regeneration in the peripheral nervous system. To investigate the remyelinating potential of Schwann cells in vivo in the peripheral nervous system, the authors have reproduced and expanded upon a novel model of immunological demyelination in the adult rat sciatic nerve. The authors demonstrate (1) the peripheral nervous system's quantitative, regenerative response to immunological demyelination and (2) whether Schwann cells within a region of demyelination are induced to divide in the presence of demyelinated axons. METHODS: The sciatic nerves of female Sprague-Dawley rats were exposed and injected with demyelinating agent bilaterally. At 3 days (n = 3), 7 days (n = 3), and 14 days (n = 3), the animals were euthanized for histological evaluation. A second group of animals (n = 3) was similarly injected with demyelinating agent and then exposed to bromodeoxyuridine between 48 and 72 hours after the onset of demyelination. These animals were euthanized soon after the last injection of bromodeoxyuridine. The tissue was analyzed for Schwann cells (labeled with antibodies to S100) and bromodeoxyuridine assay. RESULTS: A single epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 3 days after injection, peripheral nerve demyelination and Schwann cell proliferation were evident. Maximum demyelination was seen at 7 days; however, Schwann cell proliferation and remyelination peaked at 14 days after injection. CONCLUSIONS: These studies demonstrate an immunological model of demyelination and remyelination in the peripheral nervous system and quantitatively measure regenerative potential. This model will be used to isolate nerve segments and to measure their regenerative potential when given demyelinating agent after acute contusion and transection injuries.
PMID: 19483567
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Hawkins JS,Casey BM,Lo JY,Moss K,McIntire DD,Leveno KJ
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. jshawkin@uci.edu
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Weekly compared with daily blood glucose monitoring in women with diet-treated gestational diabetes.
Obstet Gynecol. 2009 Jun;113(6):1307-12
OBJECTIVE: To estimate whether daily blood glucose self-monitoring reduces macrosomia when compared with weekly office testing in women with gestational diabetes. METHODS: Between January 1991 and December 1997, standard treatment at our hospital for women with diet-treated gestational diabetes included routine office monitoring of fasting blood glucose. Beginning in January 1998, blood glucose self-monitoring (four times daily) became the standard management. Women with diet-treated gestational diabetes who underwent routine office-based monitoring of fasting glucose values were compared with similar women who used blood glucose self-monitoring. The outcomes of interest were birthweight at or above 4,000 g and large for gestational age (LGA) in relation to the method of blood glucose self-monitoring. RESULTS: A total of 315 women used daily blood glucose self-monitoring, and they were compared with 675 women with weekly office-based glucose testing. Women with daily blood glucose self-monitoring had fewer macrosomic (29.5% compared with 21.9%, P=.013) and LGA neonates (34.4% compared with 23.1%, P < or = .001) and gained significantly less weight (median 0.56, interquartile range 0.22-1.08 lb per week compared with 0.74, interquartile range 0.33-1.17 lb per week, P=.009). CONCLUSION: Daily blood glucose self-monitoring, compared with weekly office-based testing, is associated with a reduction in the incidence of macrosomia. LEVEL OF EVIDENCE: II.
PMID: 19461427
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Odgers CL,Mulvey EP,Skeem JL,Gardner W,Lidz CW,Schubert C
Department of Psychology and Social Behavior, University of California-Irvine, Irvine, CA 92697-7085, USA. codgers@uci.edu
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Capturing the ebb and flow of psychiatric symptoms with dynamical systems models.
Am J Psychiatry. 2009 May;166(5):575-82
OBJECTIVE: Psychiatric symptoms play a crucial role in psychology and psychiatry. However, little is known about how dimensions of symptoms--other than symptom level--relate to psychiatric outcomes. Until recently, methods for measuring dynamic aspects of symptoms have not been available to clinicians or researchers. The authors sought to test whether systematic patterns of change in psychiatric symptoms can be recovered across weekly assessments of individuals at high risk for violence. A secondary objective was to explore whether dynamic features of symptoms (specifically, oscillation speed and dysregulation) are concurrently associated with violence, an important indicator of functional impairment for these individuals. METHOD: Participants (N=132) were drawn from a sample of patients evaluated at the emergency room of an urban psychiatric hospital. Patients actuarially classified as being at high risk for violence were eligible for participation in the study. Participants and collateral informants were interviewed weekly for 26 weeks following an acute psychiatric evaluation. Psychiatric symptoms were assessed using the Brief Symptom Inventory. Measures of symptom fluctuation and regulation were derived using dynamical systems models. Involvement in violence was assessed using self, informant, and official reports. RESULTS: Individuals' symptom dynamics were recovered by a linear oscillator model that described how quickly symptoms oscillated and whether symptoms were amplifying or moving back toward equilibrium across time. Patterns of rapid symptom fluctuation and symptom amplification were concurrently associated with violence. CONCLUSIONS: Psychiatric researchers and clinicians have long been interested in adopting more dynamic approaches to understanding symptom change. This study is the first to demonstrate that systematic fluctuations in symptom patterns may be captured by dynamic models. Moreover, the concurrent association between symptom dynamics and violence suggests avenues for future research to test how features of symptom fluctuation could affect behavior.
PMID: 19369320
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