Head E,Corrada MM,Kahle-Wrobleski K,Kim RC,Sarsoza F,Goodus M,Kawas CH
Institute of Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA. ehead@uci.edu
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Synaptic proteins, neuropathology and cognitive status in the oldest-old.
Neurobiol Aging. 2009 Jul;30(7):1125-34
An increasing number of individuals in our population are surviving to over 90 years and a subset is at risk for developing dementia. However, senile plaque and neurofibrillary tangle pathology do not consistently differentiate individuals with and without dementia. Synaptic protein loss is a feature of aging and dementia and may dissociate 90+ individuals with and without dementia. Synaptophysin (SYN), postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were studied in the frontal cortex of an autopsy series of 32 prospectively followed individuals (92-105 years) with a range of cognitive function. SYN protein levels were decreased in individuals with dementia and increased in those with clinical signs of cognitive impairment insufficient for a diagnosis of dementia. SYN but neither PSD-95 nor GAP-43 protein levels were significantly correlated with mini-mental status examination (MMSE) scores. Frontal cortex SYN protein levels may protect neuronal function in oldest-old individuals and reflect compensatory responses that may be involved with maintaining cognition.
PMID: 18006193
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Abolhoda A,Bui TD,Milliken JC,Wirth GA
Department of Surgery, Division of Cardiothoracic Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA. aabolhod@uci.edu
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Pedicled latissimus dorsi muscle flap: routine use in high-risk thoracic surgery.
Tex Heart Inst J. 2009;36(4):298-302
Bronchopleural fistula and empyema are serious complications after thoracic surgical procedures, and their prevention is paramount. Herein, we review our experience with routine prophylactic use of the pedicled ipsilateral latissimus dorsi muscle flap. From January 2004 through February 2006, 10 surgically high-risk patients underwent intrathoracic transposition of this muscle flap for reinforcement of bronchial-stump closure or obliteration of empyema cavities. Seven of the patients were chronically immunosuppressed, 5 were severely malnourished (median preoperative serum albumin level, 2.4 g/dL), and 5 had severe underlying obstructive pulmonary disease (median forced expiratory volume in 1 second, 44% of predicted level). Three upper lobectomies and 1 completion pneumonectomy were performed in order to treat massive hemoptysis that was secondary to complex aspergilloma. One patient underwent left pneumonectomy due to ruptured-cavitary primary lung lymphoma. One upper lobectomy was performed because of necrotizing, localized Mycobacterium avium-intracellulare infection. One patient underwent right upper lobectomy and main-stem bronchoplasty for carcinoma after chemoradiation therapy. In 3 patients, the pedicled latissimus dorsi muscle was used to obliterate chronic empyema cavities and to buttress the closure of underlying bronchopleural fistulas. No operative deaths or recurrent empyemas resulted. Two patients retained peri-flap air that required no surgical intervention. We conclude that the use of transposed pedicled latissimus dorsi muscle flap effectively and reliably prevents clinically overt bronchopleural fistula and recurrent empyema. We advocate its routine use in first-time and selected reoperative thoracotomies in patients who are undergoing high-risk lung resection or reparative procedures.
PMID: 19693302
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Rosenbaum A,Kain ZN,Larsson P,Lönnqvist PA,Wolf AR
Department of Anesthesiology & Perioperative Care, University of California Irvine, Orange, CA, USA.
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The place of premedication in pediatric practice.
Paediatr Anaesth. 2009 Sep;19(9):817-28
Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro-con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.
PMID: 19691689
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Patterson JV,Sandman CA,Ring A,Jin Y,Bunney WE
Department of Psychiatry and Human Behavior, University of California at Irvine, Irvine, California 92868, USA. jvpatter@uci.edu
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An initial report of a new biological marker for bipolar disorder: P85 evoked brain potential.
Bipolar Disord. 2009 Sep;11(6):596-609
OBJECTIVES: Progress toward understanding the neurobiological and genetic underpinnings of bipolar disorder has been limited by the scarcity of potential biological markers that predict its occurrence. A measure of the integrity of brain inhibitory function, sensory gating, measured using the amplitude of the evoked potential at 50 ms to the first of two paired clicks divided by the response to the second, has been characterized as a biological marker for schizophrenia. Currently, no such biological marker exists for bipolar disorder. The goal of this research was to determine how gating of an auditory brain potential at 85 ms (P85), not previously examined in sensory gating studies, differentiated control and patient groups. METHODS: P50 and P85 auditory evoked potentials were collected from individuals diagnosed with schizoaffective disorder (n = 45), paranoid schizophrenia (n = 66), and bipolar I disorder (n = 42) using DSM-IV criteria and the Structured Clinical Interview for DSM-IV; and from 56 healthy controls. RESULTS: The P85 gating ratio was significantly larger in the bipolar disorder group compared to each of the other groups (F(3,204) = 5.47, p = 0.001, and post-hoc tests). The P50 gating ratio was significantly larger for the schizoaffective group than for the control group (F(3,204) = 2.81, p = 0.040), but did not differ from the ratio for the schizophrenia, paranoid type (p = 0.08) and bipolar groups. CONCLUSIONS: The previously unstudied P85 gating ratio may provide a new marker specific to bipolar disorder. The findings will promote further studies to investigate the unique contribution of this measure as an endophenotype.
PMID: 19689502
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McLaren CE,Chen WP,Nie K,Su MY
Department of Epidemiology, University of California, Irvine, 224 Irvine Hall, Irvine, CA 92697-7550, USA. cmclaren@uci.edu
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Prediction of malignant breast lesions from MRI features: a comparison of artificial neural network and logistic regression techniques.
Acad Radiol. 2009 Jul;16(7):842-51
RATIONALE AND OBJECTIVES: Dynamic contrast-enhanced magnetic resonance imaging is a clinical imaging modality for the detection and diagnosis of breast lesions. Analytic methods were compared for diagnostic feature selection and the performance of lesion classification to differentiate between malignant and benign lesions in patients. MATERIALS AND METHODS: The study included 43 malignant and 28 benign histologically proved lesions. Eight morphologic parameters, 10 gray-level co-occurrence matrix texture features, and 14 Laws texture features were obtained using automated lesion segmentation and quantitative feature extraction. Artificial neural network (ANN) and logistic regression analysis were compared for the selection of the best predictors of malignant lesions among the normalized features. RESULTS: Using ANN, the final four selected features were compactness, energy, homogeneity, and Law_LS, with an area under the receiver-operating characteristic curve (AUC) of 0.82 and accuracy of 0.76. The diagnostic performance of these four features computed on the basis of logistic regression yielded an AUC of 0.80 (95% confidence interval [CI], 0.688-0.905), similar to that of ANN. The analysis also showed that the odds of a malignant lesion decreased by 48% (95% CI, 25%-92%) for every increase of 1 standard deviation in the Law_LS feature, adjusted for differences in compactness, energy, and homogeneity. Using logistic regression with z-score transformation, a model composed of compactness, normalized radial length entropy, and gray-level sum average was selected, and it had the highest overall accuracy, 0.75, among all models, with an AUC of 0.77 (95% CI, 0.660-0.880). When logistic modeling of transformations using the Box-Cox method was performed, the most parsimonious model with predictors compactness and Law_LS had an AUC of 0.79 (95% CI, 0.672-0.898). CONCLUSION: The diagnostic performance of models selected by ANN and logistic regression was similar. The analytic methods were found to be roughly equivalent in terms of predictive ability when a small number of variables were chosen. The robust ANN methodology uses a sophisticated nonlinear model, while logistic regression analysis provides insightful information to enhance the interpretation of the model features.
PMID: 19409817
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Deshmukh-Rane SA,Wu ML
Department of Pathology and Laboratory Medicine, University of California Irvine Medical Center, Orange, CA 92868, USA.
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Pseudolipomatosis affects specimens from endometrial biopsies.
Am J Clin Pathol. 2009 Sep;132(3):374-7
Pseudolipomatosis refers to optically clear vacuoles that artifactually contaminate specimens, and it most commonly affects the gastrointestinal tract. Pseudolipomatosis closely resembles adult white fat and is of group "A" or "B" when vacuoles have mild or marked variation in size, respectively. Pseudolipomatosis has yet to be reported to occur in the endometrium. Pseudolipomatosis in the endometrium might be easily mistaken for extrauterine adipocytes and misdiagnosed as perforation. We retrospectively reviewed 50 consecutive specimens from endometrial biopsies to determine the prevalence of endometrial pseudolipomatosis and whether pseudolipomatosis was related to perforation. All 50 specimens contained pseudolipomatosis of group "B," and lacked extrauterine tissue. To our knowledge, all patients lacked clinical evidence of perforation at follow-up. Pseudolipomatosis commonly affects specimens from endometrial biopsies and is likely unrelated to perforation. Awareness of pseudolipomatosis is necessary to avoid misdiagnosing uterine perforation.
PMID: 19687313
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Young JL,Liss MA,Szabo RJ
Department of Urology, University of California, Irvine, 92868, USA. jlyoung@uci.edu
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Sepsis due to fluoroquinolone-resistant Escherichia coli after transrectal ultrasound-guided prostate needle biopsy.
Urology. 2009 Aug;74(2):332-8
OBJECTIVES: To report a series of patients with sepsis due to fluoroquinolone-resistant Escherichia coli after prostate needle biopsy across 4 hospitals in southern California. METHODS: Five patients presented with fever and blood cultures positive for fluoroquinolone-resistant E. coli after prostate needle biopsy with pre-procedure fluoroquinolone antimicrobial prophylaxis. The cases are described and the published data reviewed. RESULTS: Of the 5 patients, 1 was treated at Hoag Memorial Hospital in 2008, 2 were treated at the Long Beach Veterans Affairs Medical Center, 1 was treated at Kaiser Permanente Hospital in 2007, and 1 presented to University of California, Irvine, Medical Center in 2006. All patients received an oral fluoroquinolone antibiotic the morning of or 1 hour before biopsy. Of the 5 patients, 4 also received gentamicin intramuscularly before biopsy. CONCLUSIONS: The estimated incidence of sepsis was 0.1%-0.9%, assuming patients reported to the hospital at which the biopsy was performed. From a review of the published data, we recommend a fluoroquinolone antibiotic before and after biopsy for < or =24 hours. From our findings, if the patient has taken a fluoroquinolone antibiotic in the past 8 months, a second- or third-generation cephalosporin should be used or an aminoglycoside (1.5-2 mg/kg intramuscularly) with metronidazole or clindamycin. A carbapenem should be substituted if the patient has a history of infections with extended-spectrum beta-lactamase producers. Cases of fluoroquinolone-resistant E. coli should be tracked in a nationalized database.
PMID: 19464041
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Cole SA
Department of Criminology, Law & Society, 2340 Social Ecology II, University of California, Irvine, CA 92697-7080, U.S.A. scole@uci.edu
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Cultural consequences of miscarriages of justice.
Behav Sci Law. 2009;27(3):431-49
Social science scholarship has tended to focus more on the causes than the consequences of miscarriages of justice. Within the literature on consequences, the overwhelming emphasis has been on individual consequences: psychological and material impacts on the wrongly convicted individual and, in some cases, other indirectly impacted individuals such as family members of the wrongly convicted and victims of the true perpetrator's future crimes. Some attention has been devoted to social harms, the impact of miscarriages of justice on the broader society within which they are situated, such as the undermining of the legitimacy of the criminal justice system. This paper focuses on what are called here cultural consequences of miscarriages of justice: the way in which some high-profile miscarriages of justice can shape the public's beliefs about some of the most basic "facts" about crime, such as the nature, prevalence, or even existence of certain categories of crime and the types of individual who tend to perpetrate particular types of crime. In this way, the paper argues, miscarriages of justice may have hitherto underexplored consequences: reshaping, based on false premises, the public's belief about the very nature of crime itself. This paper discusses three cases studies of miscarriages of justice that for varying periods of time created widespread false beliefs about the nature of crime in large segments of the public. The paper concludes by noting that the "righting" of these false beliefs was in most cases fortuitous. This suggests that unexposed miscarriages of justice may still be shaping popular beliefs about the nature of crime, and aspects of the public's current conception of crime may yet be based on false premises.
PMID: 19402029
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Finley DS,Calvert VS,Inokuchi J,Lau A,Narula N,Petricoin EF,Zaldivar F,Santos R,Tyson DR,Ornstein DK
Department of Urology, University of California-Irvine, Orange, California, USA.
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Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness.
J Urol. 2009 Oct;182(4):1621-7
PURPOSE: Adipose tissue has been suggested to contribute to the pathogenesis of various disease states, including prostate cancer. We investigated the association of cytokines and growth factors secreted by periprostatic adipose tissue with pathological features of aggressive prostate cancer. MATERIALS AND METHODS: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy and cultured for 24 hours to generate conditioned medium or snap frozen immediately for functional signaling profiling. Multiplex analysis of the periprostatic adipose tissue conditioned medium was used to detect cytokine levels and compared to patient matched serum from 7 patients. Interleukin-6 in serum and periprostatic adipose tissue conditioned medium was further analyzed by enzyme-linked immunosorbent assay and correlated with clinical variables, such as age, body mass index and Gleason score, in 45 patients. Interleukin-6 expression in periprostatic adipose tissue was determined by immunohistochemistry. Reverse phase protein microarray technology was used to analyze cell signaling networks in periprostatic adipose tissue. RESULTS: Interleukin-6 in periprostatic adipose tissue conditioned medium was approximately 375 times greater than that in patient matched serum and levels correlated with pathological grade. This finding was further extended by cell signaling analysis of periprostatic adipose tissue, which showed greater phosphorylation on Stat3 with high grade tumors (any component of Gleason score 4 or 5). CONCLUSIONS: Higher Gleason score correlated with high levels of conditioned medium derived interleukin-6. Moreover, cell signaling analysis of periprostatic adipose tissue identified activated signaling molecules, including STAT3, that correlated with Gleason score. Since STAT3 is interleukin-6 regulated, these findings suggest that periprostatic adipose tissue may have a role in modulating prostate cancer aggressiveness by serving as a source of interleukin-6. Also, we found low numbers of inflammatory cells in the fat, suggesting that adipocytes are the major secretors of interleukin-6.
PMID: 19683746
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Rudkin SE,Langdorf MI,Oman JA,Kahn CA,White H,Anderson CL
Department of Emergency Medicine, University of California, Irvine, Orange, CA 92868, USA. srudkin@uci.edu
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The worsening of ED on-call coverage in California: 6-year trend.
Am J Emerg Med. 2009 Sep;27(7):785-91
To reassess problems with on-call physician coverage in California, we repeated our anonymous 2000 survey of the California chapter of the American College of Emergency Physicians. Physicians responded from 77.4% of California emergency departments (EDs), 51.0% of ED directors, and 34% of those surveyed. Of 21 specialties, on-call availability worsened since 2000 for 9, was unchanged for 11, and improved for 1. Of ED directors, 54% report medical staff rules require on-call duty, down from 72% in 2000. Hospitals have increased specialist on-call payments (from 21% to 35%, with 75% paying at least one specialty). Most emergency physicians (80.3%) report insurance status negatively affects on-call physician responsiveness, up from 42% in 2000. Emergency departments with predominantely minority or uninsured patients had fewer specialists and more trouble accessing them. Insurance status has a major negative effect on ED consultation and follow-up care. The on-call situation in California has worsened substantially in 6 years.
PMID: 19683105
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Wallace DC,Fan W
Organizational Research Unit for Molecular and Mitochondrial Medicine and Genetics, University of California at Irvine, Irvine, California 92697, USA. dwallace@uci.edu
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The pathophysiology of mitochondrial disease as modeled in the mouse.
Genes Dev. 2009 Aug 1;23(15):1714-36
It is now clear that mitochondrial defects are associated with a plethora of clinical phenotypes in man and mouse. This is the result of the mitochondria's central role in energy production, reactive oxygen species (ROS) biology, and apoptosis, and because the mitochondrial genome consists of roughly 1500 genes distributed across the maternal mitochondrial DNA (mtDNA) and the Mendelian nuclear DNA (nDNA). While numerous pathogenic mutations in both mtDNA and nDNA mitochondrial genes have been identified in the past 21 years, the causal role of mitochondrial dysfunction in the common metabolic and degenerative diseases, cancer, and aging is still debated. However, the development of mice harboring mitochondrial gene mutations is permitting demonstration of the direct cause-and-effect relationship between mitochondrial dysfunction and disease. Mutations in nDNA-encoded mitochondrial genes involved in energy metabolism, antioxidant defenses, apoptosis via the mitochondrial permeability transition pore (mtPTP), mitochondrial fusion, and mtDNA biogenesis have already demonstrated the phenotypic importance of mitochondrial defects. These studies are being expanded by the recent development of procedures for introducing mtDNA mutations into the mouse. These studies are providing direct proof that mtDNA mutations are sufficient by themselves to generate major clinical phenotypes. As more different mtDNA types and mtDNA gene mutations are introduced into various mouse nDNA backgrounds, the potential functional role of mtDNA variation in permitting humans and mammals to adapt to different environments and in determining their predisposition to a wide array of diseases should be definitively demonstrated.
PMID: 19651984
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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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