Rutherglen C,Burke P
Engineering Gateway 2232, Irvine, CA 92697-2625, USA. pburke@uci.edu
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Nanoelectromagnetics: circuit and electromagnetic properties of carbon nanotubes.
Small. 2009 Apr;5(8):884-906
This Review presents a discussion of the electromagnetic properties of nanoscale electrical conductors, which are quantum mechanical one-dimensional systems. Of these, carbon nanotubes are the most technologically advanced example, and are discussed mainly in this paper. The properties of such systems as transmission electron microscopy waveguides for on-chip signal propagation and also the radiation properties of such systems are discussed. This work is primarily aimed at microwave, nanometer-wave, and THz electronics. However, the use of nanotubes as antennas in the IR and optical frequency range is not precluded on first principles and remains an open research area.
PMID: 19358165
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Zell JA,Pelot D,Chen WP,McLaren CE,Gerner EW,Meyskens FL
Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA. jzell@uci.edu
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Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas.
Cancer Prev Res (Phila Pa). 2009 Mar;2(3):209-12
Nonsteroidal anti-inflammatory drugs (NSAID) have been associated with adverse cardiovascular (CV) outcomes in cancer prevention and other clinical trials. A recent meta-analysis suggested that baseline CV risk is associated with NSAID-associated adverse CV events. We evaluated the effect of baseline CV risk on adverse CV events in a phase III trial of difluoromethylornithine (DFMO) plus the NSAID sulindac versus placebo in preventing colorectal adenomas. Trial data were analyzed to determine baseline CV risk. CV toxicity outcomes were then assessed overall and excluding high CV-risk patients. Baseline CV risk scores were evenly distributed within our overall trial population of 184 placebo (low risk, 27%; moderate risk, 34%; high risk, 39%) and 191 DFMO/sulindac (low risk, 30%; moderate risk, 29%; high risk, 41%) patients. In patients with a high baseline CV risk, the number of adverse CV events was greater among DFMO/sulindac (n = 9) than among placebo (n = 3) patients. Excluding patients with a high baseline CV risk, the numbers of adverse CV events were similar in the DFMO/sulindac (n = 7) and placebo (n = 6) arms. A high CV risk score at baseline may confer an increased risk of CV events associated with treatment with DFMO/sulindac, and a low baseline score may not increase this risk. These results have implications for future NSAID-based cancer prevention clinical trials.
PMID: 19258540
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Martiny AC,Huang Y,Li W
Department of Earth System Science, University of California, Irvine, 92697 CA, USA. amartiny@uci.edu
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Occurrence of phosphate acquisition genes in Prochlorococcus cells from different ocean regions.
Environ Microbiol. 2009 Jun;11(6):1340-7
The cyanobacterium Prochlorococcus is the numerically dominant phototroph in oligotrophic parts of the oceans. Recently, it was shown that the distribution of phosphate acquisition genes did not match the 16S rRNA phylogeny among isolates from this group but rather appeared related to phosphate availability where the strains had been isolated. To further understand adaptation to phosphate limitation in Prochlorococcus, the distribution of phosphate acquisition genes was investigated in different ocean regions and related to local ortho-phosphate concentration. In regions characterized by less than 0.1 microM phosphate, most Prochlorococcus cells contain genes involved in phosphate uptake, regulation and utilization of organic phosphates. In contrast, most of these genes are absent in regions with more than 0.1 microM phosphate with the exception of genes involved in transport of phosphate (phoE and pstABCS) and three genes of unknown function. This pattern of phosphate acquisition genes showed no significant correspondence to the distribution of rRNA phylotypes. In addition, it was demonstrated that several genes in a separate genomic island were commonly present in low-P sites while absent in high-P sites. Overall, this study further demonstrates a linkage between environmental conditions in the ocean and genome content of Prochlorococcus.
PMID: 19187282
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Goodwin SC,Spies JB
Department of Radiological Sciences, University of California at Irvine, Orange CA 92868, USA. sgoodwin@uci.edu
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Uterine fibroid embolization.
N Engl J Med. 2009 Aug 13;361(7):690-7
PMID: 19675331
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Ashida R,Nakata B,Shigekawa M,Mizuno N,Sawaki A,Hirakawa K,Arakawa T,Yamao K
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. rashida@uci.edu
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Gemcitabine sensitivity-related mRNA expression in endoscopic ultrasound-guided fine-needle aspiration biopsy of unresectable pancreatic cancer.
J Exp Clin Cancer Res. 2009;28:83
BACKGROUND: The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). METHODS: mRNAs extracted from 35 pancreatic tubular adenocarcinoma tissues obtained by EUS-FNA before GEM-treatment were studied. mRNAs were amplified and applied to a Focused DNA Array, which was restricted to well-known genes, including GEM sensitivity-related genes, deoxycytidine kinase (dCK), human equilibrative nucleoside transporter 1 (hENT1), hENT2, dCMP deaminase, cytidine deaminase, 5'-nucleotidase, ribonucleotide reductase 1 (RRM1) and RRM2. mRNA levels were classified into high and low expression based on a cut-off value defined as the average expression of 35 samples. These 35 patients were divided into the following two groups. Patients with partial response and those with stable disease whose tumor markers decreased by 50% or more were classified as the effective group. The rest of patients were classified as the non-effective group. The relationship between GEM efficacy and mRNA expression was then examined by chi-squared test. RESULTS: Among these GEM sensitivity-related genes, dCK alone showed a significant correlation with GEM efficacy. Eight of 12 patients in the effective group had high dCK expression, whereas 16 of 23 patients in non-effective group had low dCK expressions (P = 0.0398). CONCLUSION: dCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Quantitative mRNA measurements of dCK using EUS-FNA samples are necessary for definitive conclusions.
PMID: 19531250
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Horn EJ,Gervay-Hague J
Department of Chemistry, University of California-Davis, One Shields Avenue, Davis, California 95616, USA. horne@uci.edu
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Efficient method for the preparation of peracetylated Neu5Ac2en by flash vacuum pyrolysis.
J Org Chem. 2009 Jun 5;74(11):4357-9
Peracetylated Neu5Ac2en methyl ester, an intermediate in the synthesis of the influenza neuraminidase inhibitor Relenza, has been synthesized in high yields from peracetylated Neu5Ac methyl ester by flash vacuum pyrolysis. Mechanistic evidence including deuterium labeled studies and DFT (B3LYP) calculations suggest this transformation proceeds via an intramolecular syn-elimination.
PMID: 19413276
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Duverne S,Lemaire P,Vandierendonck A
Laboratoire de Psychologie Cognitive, Université de Provence, Marseille, France. sduverne@uci.edu
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Do working-memory executive components mediate the effects of age on strategy selection or on strategy execution? Insights from arithmetic problem solving.
Psychol Res. 2008 Jan;72(1):27-38
Younger and older adults performed an inequality verification task (7+6 < 15, Yes/No?) in a control condition and in a dual-task condition where they simultaneously performed an executive-component task. Arithmetic-problem characteristics were manipulated in order to test strategy selection (i.e., choice of appropriate strategies in order to improve performance) and strategy execution (i.e., performance of the cognitive processes involved in each strategy). Results revealed that strategy selection changes with age: Older adults mainly selected one type of strategies in contrast to younger adults who used several types of strategies. These age-related changes were similar in the control and dual-task conditions. Strategy execution also changed with age, as shown by larger age-related differences on hardest problems. These age-related changes were larger in the dual-task condition, compared to the control condition. This impact of executive components as mediator of age-related changes depended on general age-related slowing. We discuss these findings in order to further understand the effects of age on arithmetic performance.
PMID: 16838186
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Tan Z
Department of Neurology, University of California Irvine School of Medicine, ZOT 4275, 100 Irvine Hall, Irvine, CA 92697 USA.
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Neural protection by naturopathic compounds-an example of tetramethylpyrazine from retina to brain.
J Ocul Biol Dis Infor. 2009 Jun;2(2):57-64
Given the advantages of being stable in the ambient environment, being permeable to the blood-brain and/or blood-eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague-Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer's disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, it would not take much preclinical data to justify bringing such therapeutic compounds to clinical trials in humans.
PMID: 19672463
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Delfino RJ,Staimer N,Tjoa T,Gillen DL,Polidori A,Arhami M,Kleinman MT,Vaziri ND,Longhurst J,Sioutas C
Department of Epidemiology, School of Medicine, University of California, Irvine, Irvine, California 92617, USA. rdelfino@uci.edu
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Air pollution exposures and circulating biomarkers of effect in a susceptible population: clues to potential causal component mixtures and mechanisms.
Environ Health Perspect. 2009 Aug;117(8):1232-8
BACKGROUND: Mechanisms involving oxidative stress and inflammation have been proposed to explain associations of ambient air pollution with cardiovascular morbidity and mortality. Experimental evidence suggests that organic components and ultrafine particles (UFP) are important. METHODS: We conducted a panel study of 60 elderly subjects with coronary artery disease living in retirement communities within the Los Angeles, California, air basin. Weekly biomarkers of inflammation included plasma interleukin-6, tumor necrosis factor-alpha soluble receptor II (sTNF-RII), soluble platelet selectin (sP-selectin), and C-reactive protein (CRP). Biomarkers of erythrocyte antioxidant activity included glutathione peroxidase-1 and superoxide dismutase. Exposures included outdoor home daily particle mass [particulate matter < 0.25, 0.25-2.5, and 2.5-10 microm in aerodynamic diameter (PM(0.25), PM(0.25-2.5), PM(2.5-10))], and hourly elemental and black carbon (EC-BC), estimated primary and secondary organic carbon (OC(pri), SOC), particle number (PN), carbon monoxide (CO), and nitrogen oxides-nitrogen dioxide (NO(x)-NO(2)). We analyzed the relation of biomarkers to exposures with mixed effects models adjusted for potential confounders. RESULTS: Primary combustion markers (EC-BC, OC(pri), CO, NO(x)-NO(2)), but not SOC, were positively associated with inflammatory biomarkers and inversely associated with erythrocyte anti-oxidant enzymes (n = 578). PN and PM(0.25) were more strongly associated with biomarkers than PM(0.25-2.5). Associations for all exposures were stronger during cooler periods when only OC(pri), PN, and NO(x) were higher. We found weaker associations with statin (sTNF-RII, CRP) and clopidogrel use (sP-selectin). CONCLUSIONS: Traffic-related air pollutants are associated with increased systemic inflammation, increased platelet activation, and decreased erythrocyte antioxidant enzyme activity, which may be partly behind air pollutant-related increases in systemic inflammation. Differences in association by particle size, OC fraction, and seasonal period suggest components carried by UFP are important.
PMID: 19672402
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García Molina P,Balaguer López E
UCI Pediátrica, Hospital Clínico Universitario, Valencia.
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[Special surfaces for managing pressure in pediatrics (II). Choice, assigned algorithm (Tarise) and management models]
Rev Enferm. 2009 Apr;32(4):14-20
Bed sores among children are an adverse effect provoked by the application of new technology adapted to pediatrics. Special surfaces for managing pressure in pediatrics are a preventive measure effective to avoid the development of these lesions. So that children benefit from this preventive measure, it must be adapted to their specific circumstances. In order for this to occur, it is fundamental to know: the specific characteristics which differentiate children from adults, and the type of special surfaces for managing pressure in pediatrics which are available on the market and to evaluate their appropriateness and effectiveness. The Group of Nurses to Improve Quality in Pediatrics at the University Clinical Hospital in Valencia has developed some tools which make it possible to manage and assign different sizes and types of special surfaces for managing pressure in pediatrics by means of a scientific method (Tarise). These are based on anthropometric measurements (Pediatric Space table) for each age range, the risk to develop a bed sore or skin ulcer due to pressure, the presence of a bed sore, the pathological seriousness and the type of special surfaces for managing pressure in pediatrics.
PMID: 19554896
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Hickok G
Department of Cognitive Sciences, Center for Cognitive Neuroscience, University of California, Irvine, CA 92697, USA. greg.hickok@uci.edu
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Eight problems for the mirror neuron theory of action understanding in monkeys and humans.
J Cogn Neurosci. 2009 Jul;21(7):1229-43
The discovery of mirror neurons in macaque frontal cortex has sparked a resurgence of interest in motor/embodied theories of cognition. This critical review examines the evidence in support of one of these theories, namely, that mirror neurons provide the basis of action understanding. It is argued that there is no evidence from monkey data that directly tests this theory, and evidence from humans makes a strong case against the position.
PMID: 19199415
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Potkin SG,Guffanti G,Lakatos A,Turner JA,Kruggel F,Fallon JH,Saykin AJ,Orro A,Lupoli S,Salvi E,Weiner M,Macciardi F,
Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, United States of America.
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Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer's Disease.
PLoS One. 2009;4(8):e6501
BACKGROUND: With the exception of APOE epsilon4 allele, the common genetic risk factors for sporadic Alzheimer's Disease (AD) are unknown. METHODS AND FINDINGS: We completed a genome-wide association study on 381 participants in the ADNI (Alzheimer's Disease Neuroimaging Initiative) study. Samples were genotyped using the Illumina Human610-Quad BeadChip. 516,645 unique Single Nucleotide Polymorphisms (SNPs) were included in the analysis following quality control measures. The genotype data and raw genetic data are freely available for download (LONI, http://www.loni.ucla.edu/ADNI/Data/). Two analyses were completed: a standard case-control analysis, and a novel approach using hippocampal atrophy measured on MRI as an objectively defined, quantitative phenotype. A General Linear Model was applied to identify SNPs for which there was an interaction between the genotype and diagnosis on the quantitative trait. The case-control analysis identified APOE and a new risk gene, TOMM40 (translocase of outer mitochondrial membrane 40), at a genome-wide significance level ofPMID: 19668339
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Liu JZ,Pezeshki M,Raffatellu M
Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA, USA; Institute for Immunology, University of California Irvine, Irvine, CA, USA.
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Th17 cytokines and host-pathogen interactions at the mucosa: Dichotomies of help and harm.
Cytokine. 2009 Aug 6;:
The mucosal surfaces are often the first site of interaction between pathogenic microorganisms and the host. Activation of the mucosal immune response has the important function of containing an infection and preventing dissemination of pathogens to systemic sites (barrier function). Numerous lines of evidence suggest that the barrier function is orchestrated by a subset of cytokines (interleukin (IL-)17 and IL-22), which belong to the Th17 family. IL-17 and IL-22 induce expression of antimicrobial peptides and neutrophil chemoattractants at mucosal sites, and thus play an important role in controlling mucosal infections. However, there is increasing evidence that mucosal pathogens achieve greater colonization during inflammation because they are resistant to a subset of these antimicrobial responses. In this review we compare the antimicrobial responses elicited by Th17 cytokines during mucosal infections with four different pathogens: Klebsiella pneumoniae, Citrobacter rodentium, Candida albicans and Salmonella typhimurium. We will then discuss which responses may constitute the mucosal barrier, thus providing a benefit to the host, and which ones may promote the colonization of pathogens, thereby providing a benefit to the microbes.
PMID: 19665391
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Cobb JP,Ognibene FP,Ingbar DH,Mann HJ,Hoyt DB,Angus DC,Thomas AV,Danner RL,Suffredini AF
From the Center for Critical Illness and Health Engineering (JPC), Washington University, St. Louis, MO; Critical Care Medicine Department and the Functional Genomics and Proteomics Facility (RLD, AFS), Clinical Center (FPO), National Institutes of Health, Department of Health and Human Services, Bethesda, MD; Pulmonary, Allergy, and Critical Care Division, Department of Medicine (DHI), and College of Pharmacy (HJM), University of Minnesota, Minneapolis, MN; Department of Surgery (DBH), University of California-Irvine, Orange, CA; CRISMA Laboratory and Department of Critical Care Medicine (DCA), University of Pittsburgh, PA; Pulmonary Division (AVT), Department of Medicine, Howard University College of Medicine, Washington, DC.
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Forging a critical alliance: Addressing the research needs of the United States critical illness and injury community*
Crit Care Med. 2009 Aug 5;:
PMID: 19661806
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Vaziri ND,Zhou XJ
Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Bldg 53 Rm 125 Rt 81, Orange, CA 92868, USA. ndvaziri@uci.edu
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Potential mechanisms of adverse outcomes in trials of anemia correction with erythropoietin in chronic kidney disease.
Nephrol Dial Transplant. 2009 Apr;24(4):1082-8
PMID: 18987263
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Romero J,Vari A,Gambarrutta C,Oliviero A
Intensive Care Unit and Neurology Unit, UCI, Hospital Nacional de Paraplejicos, Finca "La Peraleda" s/n, 45071, Toledo, Spain, fjromero@sescam.jccm.es.
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Tracheostomy timing in traumatic spinal cord injury.
Eur Spine J. 2009 Aug 5;:
The study conducted is the retrospective study and the main objective is to evaluate the benefits and safety of early versus late tracheostomy in traumatic spinal cord injury (SCI) patients requiring mechanical ventilation. Tracheostomy offers many advantages in critical patients who require prolonged mechanical ventilation. Despite the large amount of patients treated, there is still an open debate about advantages of early versus late tracheostomy. Early tracheostomy following the short orotracheal intubation is probably beneficial in appropriately selected patients. It is a retrospective clinical study and we evaluated clinical records of 152 consecutive trauma patients who required mechanical ventilation and who received tracheostomy. The results show that the early placement (before day 7 of mechanical ventilation) offers clear advantages for shortening of mechanical ventilation, reducing ICU stay and lowering rates of severe orotracheal intubation complication, such as tracheal granulomas and concentric tracheal stenosis. On the other hand, we could not demonstrate that early tracheostomy avoids neither risk of ventilator-associated pneumonia nor the mortality rate. In SCI patients, the early tracheostomy was associated with shorter duration of mechanical ventilation, shorter length of ICU stay and decreased laryngotracheal complications. We conclude by suggesting early tracheostomy in traumatic SCI patients who are likely to require prolonged mechanical ventilation.
PMID: 19655178
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Udar N,Atilano SR,Small K,Nesburn AB,Kenney MC
Department of Ophthalmology, The Eye Institute, University of California Irvine, Orange, CA, USA.
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SOD1 haplotypes in familial keratoconus.
Cornea. 2009 Sep;28(8):902-7
PURPOSE: We reported previously a 7-base intronic deletion close to the intron/exon junction of the SOD1 gene in 2 separate families with an autosomal-dominant form of keratoconus. The goal of this study was to determine if the 2 families (families A and H) shared a common haplotype by identifying closely linked new microsatellite markers flanking the SOD1 gene. METHODS: Total genomic DNA was extracted from the blood of available members of families A and H. The DNA was amplified by polymerase chain reaction and digested with HpyCH4 III. A genomic contig was first constructed flanking the human SOD1 gene on chromosome 21q22.1-21q22.11. New polymorphic microsatellite markers were identified. All available individuals from the 2 families were genotyped using a set of 7 different markers (SOD1NU10, SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU13, SOD1NU8, and SOD1NU9) to identify phase and the disease haplotype was constructed. RESULTS: Five of the 7 markers are novel (SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU8, and SOD1NU9). Family A is a 3-generation family and the disease haplotype was inferred based on segregation data for 7 different markers. Family H shared only 3 of the disease-associated alleles (SOD1NU1, SOD1NU2, and SOD1NU13) compared with family A. CONCLUSION: Based on the dissimilarity of disease-associated alleles, the 2 families do not appear to share the same haplotype and therefore are not closely related. This strongly supports the uniqueness of the 7-base deletion in intron 2 of the SOD1 gene to the keratoconus phenotype.
PMID: 19654524
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Wiglesworth A,Austin R,Corona M,Schneider D,Liao S,Gibbs L,Mosqueda L
Program in Geriatrics, School of Medicine, University of California at Irvine, Irvine, California, USA. awiglesw@uci.edu
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Bruising as a marker of physical elder abuse.
J Am Geriatr Soc. 2009 Jul;57(7):1191-6
OBJECTIVES: To describe bruising as a marker of physical elder abuse. DESIGN: Consenting older adults were examined to document location and size of bruises and assess whether they were inflicted during physical abuse. An expert panel confirmed physical abuse. Findings were compared with results of an earlier study of accidental bruising in older adults. SETTING: Residences of participants. PARTICIPANTS: Sixty-seven adults aged 65 and older reported to Adult Protective Services (APS) for suspected physical elder abuse. MEASUREMENTS: Age, sex, ethnicity, race, functional status, medical conditions, cognitive status, history of falls, bruise size and location, recall of cause, and responses to Revised Conflicts Tactics Scale and Elder Abuse Inventory. RESULTS: Seventy-two percent (n=48) of older adults who had been physically abused within 30 days before examination had bruises. The physically abused older adults had significantly larger bruises; more of them knew the cause of their bruises (43 (89.6%) vs 16 (23.5%) of the comparison group); and they were significantly more likely to have bruises on the face, lateral aspect of the right arm and the posterior torso (including back, chest, lumbar, and gluteal regions) than older adults from an earlier study who had not been abused (n=68). CONCLUSION: Bruises that occur as a result of physical elder mistreatment are often large (>5 cm) and on the face, lateral right arm, or posterior torso. Older adults with bruises should be asked about the cause of the bruises to help ascertain whether physical abuse occurred.
PMID: 19558476
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Murgu S,Colt HG
Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, Irvine, California 92868, USA. smurgu@uci.edu
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Morphometric bronchoscopy in adults with central airway obstruction: case illustrations and review of the literature.
Laryngoscope. 2009 Jul;119(7):1318-24
The severity of airway narrowing impacts ventilatory function, quality of life, and choice of therapy for patients with central airway obstruction. The quantification of airway caliber remains a subjective estimate that depends on patient positioning, technique, and operator experience. In this article, we describe how morphometric bronchoscopy, a software processing method whereby bronchoscopic digital images are analyzed in order to measure airway lumen diameter, can be used to objectively quantify the degree of airway narrowing in adult patients with central airway obstruction.
PMID: 19444886
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Potkin SG,Turner JA,Fallon JA,Lakatos A,Keator DB,Guffanti G,Macciardi F
Department of Psychiatry and Human Behavior, Brain Imaging Center, University of California, Irvine, CA 92617, USA. sgpotkin@uci.edu
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Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia.
Mol Psychiatry. 2009 Apr;14(4):416-28
We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in an independent study provided additional support for this association. We have both discovered and verified the association of two genes, RSRC1 and ARHGAP18, with schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs) related to these genes as consistently associated with the phenotypic variation. To control for the risk of false positives, the empirical P-value for association significance was calculated using permutation testing. The quantitative phenotype was Blood-Oxygen-Level Dependent (BOLD) Contrast activation in the left dorsal lateral prefrontal cortex measured during a working memory task. The differential distribution of SNPs associated with these two genes in cases and controls was then corroborated in a larger, independent sample of patients with schizophrenia (n=82) and healthy controls (n=91), thus suggesting a putative etiological function for both genes in schizophrenia. Up until now these genes have not been linked to any neuropsychiatric illness, although both genes have a function in prenatal brain development. We introduce the use of functional magnetic resonance imaging activation as a quantitative phenotype in conjunction with genome-wide association as a gene discovery tool.
PMID: 19065146
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Bai Y,Jabbari B,Ye S,Campese VM,Vaziri ND
Division of Nephrology and Hypertension, University of California-Irvine, 101 The City Drive, Orange, CA 92868, USA.
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Regional expression of NAD(P)H oxidase and superoxide dismutase in the brain of rats with neurogenic hypertension.
Am J Nephrol. 2009;29(5):483-92
BACKGROUND: Single injection of small quantities of phenol into the kidney cortex causes hypertension which is mediated by renal afferent sympathetic pathway activation. This phenomenon can be prevented by superoxide dismutase (SOD) infusion in the lateral ventricle, suggesting the role of superoxide (O(2)(-).) in noradrenergic control of arterial pressure. Since NAD(P)H oxidase is a major source of O(2)(-)., we tested the hypothesis that hypertension in this model may be associated with upregulation of NAD(P)H oxidase in relevant regions of brain. METHODS: NAD(P)H oxidase subunits, mitochondrial (MnSOD) and cytoplasmic (CuZnSOD) SOD were measured in rats 4 weeks after injection of phenol or saline in the left kidney cortex. RESULTS: Phenol-injected rats exhibited hypertension, upregulation of gp91(phox), p22(phox), p47(phox) and p67(phox) in the medulla, gp91(phox) and p22(phox) in pons and gp91(phox) in hypothalamus. This was associated with upregulation of MnSOD with little change in CuZnSOD. CONCLUSIONS: Chronic hypertension in phenol-injected rats is associated with upregulation of NAD(P)H oxidase and hence increased O(2)(-). production capacity in the key regions of the brain involved in regulation of blood pressure. Since reactive oxygen species can intensify central noradrenergic activity, the observed maladaptive changes may contribute to the genesis and maintenance of the associated hypertension.
PMID: 19047792
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McGaugh JL,Roozendaal B
Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800, USA. JLMCGAUG@UCI.EDU
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Drug enhancement of memory consolidation: historical perspective and neurobiological implications.
Psychopharmacology (Berl). 2009 Jan;202(1-3):3-14
INTRODUCTION: Studies of drug enhancement of cognition began with Lashley's (Psychobiology 1:141-170, 1917) report that strychnine administered before daily training trials enhanced rats' maze learning. Many subsequent studies confirmed that finding and found that stimulant drugs also enhance the learning of a wide range of tasks. DISCUSSION: A central problem in interpreting such findings is that of distinguishing the drug effects on brain processes underlying memory formation from many other possible effects of the drugs on the behavior used to assess learning. The subsequent finding that comparable learning enhancement can be obtained by posttraining drug administration provided compelling evidence that drugs can enhance memory by acting on memory consolidation processes. Such evidence stimulated the investigation of endogenous regulation of memory consolidation by arousal-released adrenal stress hormones. CONCLUSION: Considerable evidence now indicates that such hormones regulate memory consolidation via activation of the basolateral amygdala and subsequent influences on many efferent brain regions involved in processing recent experiences. The implications of these findings for the development of cognitive enhancing drugs are discussed.
PMID: 18704369
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Amin AN,Lin J,Lenhart G,Schulman KL
University of California - Irvine, Orange, CA 92868, USA. anamin@uci.edu
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Clinical and economic outcomes in patients at risk of venous thromboembolism receiving appropriate enoxaparin or unfractionated heparin prophylaxis.
Thromb Haemost. 2009 Aug;102(2):321-6
Clinical and economic outcomes were compared following appropriate prophylaxis with enoxaparin or unfractionated heparin (UFH) in a large, real-world population of US hospitalised medical and surgical patients at risk of venous thromboembolism (VTE). Discharges from the Thomson Reuters MarketScan Hospital Drug Database (January 2004-March 2007) of patients aged > or =40 years, at risk of VTE according to the 7(th) American College of Chest Physicians (ACCP) guidelines, who spent > or =6 days in hospital and received appropriate ACCP-recommended enoxaparin or UFH prophylaxis were included. Patients with contraindications to anticoagulation were excluded. Hospital-acquired VTE, adverse events, and hospital costs for enoxaparin versus UFH were compared using univariate and multivariate analyses. Of the 5,136 discharges included, 4,014 (78%) received enoxaparin and 1,122 (22%) received UFH. Compared with UFH, enoxaparin was associated with significantly lower risk of hospital-acquired VTE (adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.30-0.86, p = 0.012), pulmonary embolism (adjusted OR 0.33, 95% CI 0.14-0.79, p = 0.013) or adverse events (adjusted OR 0.73, 95% CI 0.54-0.98, p = 0.034). Total hospital costs per discharge were lower for enoxaparin (US $16,865 +/- 10,979) than UFH (US $19,252 +/- 14,970), with a mean difference of US $2,388 in favour of enoxaparin (p < 0.001) (adjusted difference US $439, 95% CI US $ -39 to 909, p = 0.072). In patients at risk of VTE, appropriate enoxaparin prophylaxis was associated with a reduction in hospital-acquired VTE, adverse events, and costs compared with appropriate UFH prophylaxis. Increased appropriate use of enoxaparin in patients at risk of VTE may help to reduce the clinical and economic burden of this condition.
PMID: 19652883
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Lee JG
University of California Irvine Medical Center, 101 The City Drive, Building 53, Room 113, Orange, CA 92868, USA. jglee@uci.edu
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Diagnosis and management of acute cholangitis.
Nat Rev Gastroenterol Hepatol. 2009 Sep;6(9):533-41
Bacterial infection that occurs in the setting of biliary obstruction can lead to acute cholangitis, a condition characterized by fever, abdominal pain and jaundice. Choledocholithiasis is the most common cause of acute cholangitis and is often associated with bacterial infection and colonization in addition to biliary obstruction. Iatrogenic introduction of bacteria into the biliary system most commonly occurs during endoscopic retrograde cholangiopancreatography in patients with biliary obstruction. The majority of patients with acute cholangitis respond to antibiotic therapy, but endoscopic biliary drainage is ultimately required to treat the underlying obstruction. Acute cholangitis is often diagnosed using the clinical Charcot triad criteria; however, recommendations from an international consensus meeting in Tokyo produced the most comprehensive recommendations for the diagnosis and management of acute cholangitis. These guidelines enable a more accurate diagnosis of acute cholangitis than do earlier methods, and they facilitate the classification of disease as mild, moderate or severe. Although these guidelines represent a notable advance toward defining a universally accepted consensus for the definition of acute cholangitis, they have several limitations. This Review discusses current recommendations for the diagnosis of acute cholangitis and addresses the advantages and disadvantages of different modalities for the treatment of this disease.
PMID: 19652653
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Ou SH,Ziogas A,Zell JA
Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of Irvine Medical Center, Orange, California 92868-3298, USA. Ignatius.ou@uci.edu
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Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer (NSCLC) and is independent of smoking status.
J Thorac Oncol. 2009 Sep;4(9):1083-93
BACKGROUND: We previously showed that Asian ethnicity was an independent favorable prognostic factor in non-small cell lung cancer (NSCLC). Many Asian NSCLC patients were never-smokers, and never-smokers had improved survival than ever-smokers. We investigated whether Asian ethnicity is a favorable prognostic factor independent of smoking status. METHODS: Retrospective population-based study of NSCLC cases from the cancer surveillance programs of three Southern California counties from 1991 to 2005. RESULTS: A total of 20,140 NSCLC patients with known smoking status were analyzed of which 9.1% were never-smokers and 6.5% were Asians. There was a threefold increase in the percentage of Asian never-smokers as compared with ever-smokers. Asians had the highest overall survival (OS) among the 4 major ethnicities (p < 0.0001) and never-smokers had improved OS over ever-smokers (p = 0.0183) by univariate analyses. By multivariate analyses, Asian ethnicity was an independent and favorable prognostic factor for OS (versus non-Asian; hazard ratio [HR] = 0.861, 95% confidence interval [CI]: 0.808-0.918, p < 0.0001), among smokers (versus non-Asian; HR = 0.867, 95% CI: 0.807-0.931, p < 0.0001), and among never-smokers (versus non-Asian; HR = 0.841, 95% CI: 0.728-0.971, p = 0.0180). Never-smoker was a favorable prognostic factor if ethnicity was not accounted for (versus ever-smoker; HR = 0.936, 95% CI: 0.886-0.988, p = 0.0169) but was no longer an independent favorable prognostic factor (versus ever-smoker; HR = 0.953, 95% CI: 0.902-1.007, p = 0.0861) after accounting for ethnicity. CONCLUSIONS: Asian ethnicity is an independent favorable prognostic factor for OS in NSCLC regardless of smoking status.
PMID: 19652625
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