Guenther GG,Edinger AL
Department of Developmental and Cell Biology, University of California-Irvine, Irvine, CA 92697-2300, USA.
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A new take on ceramide: starving cells by cutting off the nutrient supply.
Cell Cycle. 2009 Apr 15;8(8):1122-6
Ceramide generation is increased by a broad array of signals. In general, ceramide limits cell survival and proliferation and promotes differentiation and senescence. Despite its role in the pathogenesis of multiple human diseases, ceramide's mechanism of action remains poorly defined. Understanding how this sphingolipid modulates cell physiology is therefore an important goal. Building on prior observations that ceramide induces autophagy, we demonstrate that ceramide kills cells by inducing severe bioenergetic stress secondary to nutrient transporter downregulation. In support of this model, maintaining nutrient access blocks ceramide-induced autophagy and cell death. This bioenergetic mechanism of action may explain the increased sensitivity of cancer cells to ceramide. Starvation induces quiescence in normal cells. Tumor cells, in contrast, carry oncogenic mutations that block the switch to catabolism and prevent a reduction in metabolic demand leading to a bioenergetic crisis when nutrients become scarce. We propose that the non-lethal effects of ceramide might also stem from ceramide-induced starvation. While severe nutrient stress kills cells, mild nutrient limitation slows proliferation and may contribute to the induction of senescence. In sum, our new model for ceramide action suggests that regulated nutrient transporter expression may play a previously unappreciated role in cancer and other diseases where ceramide metabolism is altered.
PMID: 19282666
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Nguyen NT,Hinojosa MW,Smith BR,Gray J,Varela E
Department of Surgery, University of California, Irvine Medical Center, 333 City Blvd. West, Suite 850, Orange, CA 92868, USA. ninhn@uci.edu
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Improvement of restrictive and obstructive pulmonary mechanics following laparoscopic bariatric surgery.
Surg Endosc. 2009 Apr;23(4):808-12
BACKGROUND: Morbidly obese patients often have impaired respiratory mechanics leading to restrictive and obstructive lung diseases. Weight loss after bariatric surgery has been shown to improve or resolve many obesity-related comorbidities. However, few studies have examined long-term changes in pulmonary mechanics after bariatric surgery. We hypothesize that pulmonary function improves after surgically induced weight loss. METHODS: We examined the pulmonary function of 104 morbidly obese patients who underwent laparoscopic gastric bypass or gastric banding. Pulmonary studies, including forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory volume at midexpiratory phase (FEV(25-75%)) were measured preoperatively and at 3-month intervals. All results are expressed as a percentage of the baseline values. RESULTS: There were 80 females and 24 males with a mean age of 41 years. The mean body mass index was 48 kg/m(2). The mean percentage of excess body weight loss at 12 months was 54%. At 12 months postoperatively, restrictive pulmonary mechanics significantly improved as demonstrated by an increase in the FEV(1) to 112% of baseline value, increase in the FVC to 109% of baseline value, increase in the PEF to 115% of baseline value, and increase in the FEV(25-75%) to 130% of baseline value. Additionally, the percentage of patients with obstructive lung pattern (FEV(1)/FVC ratio less than 0.8) decreased from 9.6% preoperatively to 1.9% postoperatively (p=0.03). CONCLUSIONS: Weight loss after laparoscopic gastric bypass significantly improves restrictive and obstructive respiratory mechanics. The improvements were observed as early as 3 months postoperatively.
PMID: 18806943
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Silman E,Langdorf MI,Rudkin S,Lotfipour S
Department of Emergency Medicine, University of California Irvine School of Medicine.
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Images in Emergency Medicine: Pediatric Spinal Cord Injury without Radiographic Abnormality.
West J Emerg Med. 2008 May;9(2):124
PMID: 19561722
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Milenkovi? T,Filippis I,Lappe M,Przulj N
Department of Computer Science, University of California Irvine, Irvine, CA, USA.
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Optimized null model for protein structure networks.
PLoS One. 2009;4(6):e5967
Much attention has recently been given to the statistical significance of topological features observed in biological networks. Here, we consider residue interaction graphs (RIGs) as network representations of protein structures with residues as nodes and inter-residue interactions as edges. Degree-preserving randomized models have been widely used for this purpose in biomolecular networks. However, such a single summary statistic of a network may not be detailed enough to capture the complex topological characteristics of protein structures and their network counterparts. Here, we investigate a variety of topological properties of RIGs to find a well fitting network null model for them. The RIGs are derived from a structurally diverse protein data set at various distance cut-offs and for different groups of interacting atoms. We compare the network structure of RIGs to several random graph models. We show that 3-dimensional geometric random graphs, that model spatial relationships between objects, provide the best fit to RIGs. We investigate the relationship between the strength of the fit and various protein structural features. We show that the fit depends on protein size, structural class, and thermostability, but not on quaternary structure. We apply our model to the identification of significantly over-represented structural building blocks, i.e., network motifs, in protein structure networks. As expected, choosing geometric graphs as a null model results in the most specific identification of motifs. Our geometric random graph model may facilitate further graph-based studies of protein conformation space and have important implications for protein structure comparison and prediction. The choice of a well-fitting null model is crucial for finding structural motifs that play an important role in protein folding, stability and function. To our knowledge, this is the first study that addresses the challenge of finding an optimized null model for RIGs, by comparing various RIG definitions against a series of network models.
PMID: 19557139
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Motoyama S,Sarai M,Harigaya H,Anno H,Inoue K,Hara T,Naruse H,Ishii J,Hishida H,Wong ND,Virmani R,Kondo T,Ozaki Y,Narula J
Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan; Division of Cardiology, University of California Irvine School of Medicine, Irvine, California.
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Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome.
J Am Coll Cardiol. 2009 Jun 30;54(1):49-57
OBJECTIVES: In a computed tomographic (CT) angiography study, we identified the characteristics of atherosclerotic lesions that were associated with subsequent development of acute coronary syndrome (ACS). BACKGROUND: The CT characteristics of culprit lesions in ACS include positive vessel remodeling (PR) and low-attenuation plaques (LAP). These 2 features have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described. METHODS: In 1,059 patients who underwent CT angiography, atherosclerotic lesions were analyzed for the presence of 2 features: PR and LAP. The remodeling index, and plaque and LAP areas and volumes were calculated. The plaque characteristics of lesions resulting in ACS during the follow-up of 27 +/- 10 months were evaluated. RESULTS: Of the 45 patients showing plaques with both PR and LAP (2-feature positive plaques), ACS developed in 10 (22.2%), compared with 1 (3.7%) of the 27 patients with plaques displaying either feature (1-feature positive plaques). In only 4 (0.5%) of the 820 patients with neither PR nor LAP (2-feature negative plaques) did ACS develop. None of the 167 patients with normal angiograms had acute coronary events (p < 0.001). ACS was independently predicted by PR and/or LAP (hazard ratio: 22.8, 95% confidence interval: 6.9 to 75.2, p < 0.001). Among 2- or 1-feature positive segments, those resulting in ACS demonstrated significantly larger remodeling index (126.7 +/- 3.9% vs. 113.4 +/- 1.6%, p = 0.003), plaque volume (134.9 +/- 14.1 mm(3) vs. 57.8 +/- 5.7 mm(3), p < 0.001), LAP volume (20.4 +/- 3.4 mm(3) vs. 1.1 +/- 1.4 mm(3), p < 0.001), and percent LAP/total plaque area (21.4 +/- 3.7 mm(2) vs. 7.7 +/- 1.5 mm(2), p = 0.001) compared with segments not resulting in ACS. CONCLUSIONS: The patients demonstrating positively remodeled coronary segments with low-attenuation plaques on CT angiography were at a higher risk of ACS developing over time when compared with patients having lesions without these characteristics.
PMID: 19555840
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Herscu G,Wilson SE
Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA. gherscu@uci.edu
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Prosthetic infection: lessons from treatment of the infected vascular graft.
Surg Clin North Am. 2009 Apr;89(2):391-401, viii
Surgical prosthetics provide unquestioned benefit to patients in maintenance of life and limb. However, complications associated with prosthetic devices continue to represent a significant source of morbidity and mortality. Even as the surgeon becomes more adept at management of infections, the bacterial characteristics change in favor of increased virulence and greater resistance to antimicrobials. Excision or retention of the prosthesis depends on the time of presentation, the microbial isolates recovered, and the extent of surrounding tissue destruction. Recent work shows improving results with in situ replacement.
PMID: 19281890
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Charvet CJ,Striedter GF
Department of Neurobiology & Behavior and Center for the Neurobiology of Learning & Memory, University of California, Irvine, California 92697, USA. ccharvet@uci.edu
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Developmental origins of mosaic brain evolution: Morphometric analysis of the developing zebra finch brain.
J Comp Neurol. 2009 May 10;514(2):203-13
In adult zebra finches (Taeniopygia guttata), the telencephalon occupies 64% of the entire brain. This fraction is similar to what is seen in parrots, but many other birds possess a significantly smaller telencephalon. The aim of the present study was to determine the developmental time course and cellular basis of telencephalic enlargement in zebra finches, and then to compare these findings with what is known about telencephalic enlargement in other birds. To this end we estimated the volumes of all major brain regions from serial sections in embryonic and post-hatching zebra finches. We also labeled proliferating cells with antibodies against proliferating cell nuclear antigen and phosphorylated histone H3. An important finding to emerge from this work is that the telencephalon of zebra finches at hatching contains a thick proliferative subventricular zone (SVZ) that extends from the subpallium into the dorsal pallium. The data also show that the onset and offset of telencephalic neurogenesis are both delayed in zebra finches relative to quail (Galliformes). This delay in neurogenesis, in conjunction with the expanded SVZ, probably accounts for most of the telencephalic enlargement in passerines such as the zebra finch. In addition, passerines enlarged their telencephalon by decreasing the proportional size of their midbrain tectum. Because the presumptive tectum is proportionally smaller in zebra finches than quail before neurogenesis begins, this difference in tectum size cannot be due to evolutionary alterations in neurogenesis timing. Collectively these findings indicate that several different developmental mechanisms underlie the evolution of a large telencephalon in passerines.
PMID: 19266567
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Kasof J
Department of Psychology and Social Behavior, School of Social Ecology, University of California, Irvine, California 92697-7085, USA. jkasof@uci.edu
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Cultural variation in seasonal depression: cross-national differences in winter versus summer patterns of seasonal affective disorder.
J Affect Disord. 2009 May;115(1-2):79-86
BACKGROUND: Research suggests that two dimensions of national culture, individualism-collectivism and power distance, predict affective responses to the seasonally varying levels of ambient sunlight that may underlie regular cycles of mood and behavior in Seasonal Affective Disorder (SAD). Specifically, negative affect is predicted by the diminished sunlight of fall-winter in countries higher in individualism and lower in power distance, and by the increased sunlight of spring-summer in countries lower in individualism and higher in power distance. This study tests whether individualism correlates positively, and power distance negatively, with the frequency of winter-SAD relative to that of summer-SAD. METHOD: A search for studies reporting frequencies of both winter-SAD and summer-SAD identified 55 samples encompassing 18 countries and 38,408 participants, including 1931 with SAD. RESULTS: The frequency of winter-SAD, relative to that of summer-SAD, correlated positively with individualism (r=.67, p=.001) and negatively with power distance (r=-.72, p=.0001). Countries in which winter-SAD was more common than summer-SAD were significantly more individualistic and less power-distant than countries in which summer-SAD was more common than winter-SAD. Results survived various tests of threats to validity. LIMITATIONS: The study is limited by the quantity, quality, diversity, and representativeness of the research under review and by its correlational design. CONCLUSIONS: Individualism and power distance are strongly related to the relative prevalence of winter-SAD and summer-SAD. Culture may play an important but previously overlooked role in the etiology of SAD.
PMID: 18849078
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Ruf IK,Houmani JL,Sample JT
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA. iruf@uci.edu
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Epstein-Barr virus independent dysregulation of UBP43 expression alters interferon-stimulated gene expression in Burkitt lymphoma.
PLoS One. 2009;4(6):e6023
Epstein-Barr virus (EBV) persists as a life-long latent infection within memory B cells, but how EBV may circumvent the innate immune response within this virus reservoir is unclear. Recent studies suggest that the latency-associated non-coding RNAs of EBV may actually induce type I (antiviral) interferon production, raising the question of how EBV counters the negative consequences this is likely to have on viral persistence. We addressed this by examining the type I interferon response in Burkitt lymphoma (BL) cell lines, the only in vitro model of the restricted program of EBV latency-gene expression in persistently infected B cells in vivo. Importantly, we observed no effect of EBV on interferon alpha-induced signaling or evidence of type I interferon production, suggesting that EBV in this latent state is silent to the cell's innate antiviral surveillance. We did uncover, however, a defect in the negative feedback control of interferon signaling in a subpopulation of BL lines as was revealed by prolonged interferon-stimulated gene transcription consistent with sustained tyrosine phosphorylation on STAT1 and STAT2. This was due to inadequate induction of expression of the ubiquitin-specific protease UBP43, which removes the ubiquitin-like ISG15 polypeptide conjugated to proteins (ISGylation) in response to type I interferons. Results here are consistent with previous findings in genetically engineered Ubp43(-/-) murine cells that UBP43 down-regulates interferon signaling, independent of its ISG15 isopeptidase activity, by precluding the protein kinase JAK1 from the interferon receptor. This natural deficiency in UBP43 expression may therefore provide a useful model to further probe the biological roles of UBP43 and ISGylation.
PMID: 19551150
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Zell JA,Ignatius Ou SH
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Survival prognostication in non-small cell lung cancer.
J Thorac Oncol. 2009 Jul;4(7):785-6
PMID: 19550241
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Chernyavsky AI,Arredondo J,Qian J,Galitovskiy V,Grando SA
University of California Irvine, United States.
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Coupling of ionic events to protein kinase signaling cascades upon activation of alpha7 nicotinic receptor: Cooperative regulation of alpha2-integrin expression and Rho-kinase activity.
J Biol Chem. 2009 Jun 23;:
Defining the signaling mechanisms and effector proteins mediating phenotypic and mechanical plasticity of keratinocytes (KCs) during wound epithelialization is one of the major goals in epithelial cell biology. The acetylcholine (ACh)-gated ion channels, or nicotinic ACh receptors (nAChRs), mediate the nicotinergic signaling that controls crawling locomotion of KCs. To elucidate relative contributions of the ionic and protein kinase-mediated events elicited due to activation of a7 nAChRs, we quantitated expression of a2-integrin gene at the mRNA and protein levels and also measured Rho-kinase activity in KCs stimulated with the a7 agonist AR-R17779 while blocking the Na+ or Ca2+ entry and/or inhibiting signaling kinases. The results demonstrated the existence of the two-component signaling systems coupling the ionic events and protein kinase signaling cascades downstream of a7 nAChR to simultaneous upregulation of a2-integrin expression and activation of Rho-kinase (ROK). The Raf/MEK1/ERK1/2 cascade upregulating a2-integrin was activated due to both Ca2+-dependent recruitment of Ca2+/calmodulin-dependent protein-kinase II (CaMKII) and protein kinase C and Ca2+-independent activation of Ras. Likewise, the PI3K-mediated activation of ROK was elicited due to both Ca2+ entry-dependent involvement of CaMKII and Ca2+-independent activation of Jak2. Thus, although the initial signals emanating from activated a7 nAChR are different in nature the pathways intersect at common effector molecules providing for a common endpoint effect. This novel paradigm of nAChR mediated coordination of the ionic and metabolic signaling events can allow an auto/paracrine ACh to simultaneously alter gene expression and induce reciprocal changes in the cytoskeleton and contractile system of KCs required to compete a particular step of wound epithelialization.
PMID: 19549780
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Berger WE,Kerwin E,Bernstein DI,Pedinoff A,Bensch G,Karafilidis J
Allergy and Asthma Associates of Southern California, Mission Viejo, California, USA. wberger@uci.edu
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Efficacy and safety evaluation of ciclesonide in subjects with mild-to-moderate asthma not currently using inhaled corticosteroids.
Allergy Asthma Proc. 30(3):304-14
Inhaled corticosteroids (ICSs) are a first-line treatment for persistent asthma. This study was designed to compare the efficacy and safety of ciclesonide (CIC) in subjects with mild-to-moderate persistent asthma not using an ICS. This was a multicenter, double-blind, parallel-group, placebo-controlled, 16-week study in subjects who were > or =12 years old, had a > or =6-month history of persistent asthma, a forced expiratory volume in 1 second (FEV(1)) of > or =60 to < or =85% predicted, and who were not using an ICS < or =30 days before study entry. Subjects were randomized to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 170); CIC, 160 microg once daily in the morning (CIC160 q.d. in the A.M.; n = 173); CIC80 b.i.d. for 4 weeks followed by CIC160 q.d. for 12 weeks (CIC80 b.i.d./CIC160 q.d.; n = 171); or placebo (n = 177). Change in FEV(1) from baseline to the average of weeks 12 and 16 (primary end point) and to week 16, A.M. peak expiratory flow, rescue albuterol use, nighttime awakenings, asthma symptom scores, and safety were evaluated. FEV(1) improved from baseline to the average of weeks 12 and 16 for CIC80 b.i.d. (+0.30L; p < 0.0001), CIC160q.d. (+0.19L; p < 0.0001), CIC80 b.i.d./CIC160 q.d. (+0.19L; p < 0.0001), and placebo (+0.06L; p = 0.0251); improvement was greatest for CIC80 b.i.d. (p < 0.01). At week 16, all CIC treatments significantly improved FEV(1) and A.M. PEF from baseline (p < 0.0001) and compared with placebo (p < or = 0.015). All treatments reduced albuterol use and nighttime awakenings and improved asthma symptom scores (p < or = 0.05 versus baseline); these improvements were greater for CIC80 b.i.d. than for placebo (p < 0.01). The incidence of adverse events was similar among treatment groups (range, 53-58%). In this study, CIC80 b.i.d. improved disease control in subjects with mild-to-moderate persistent asthma not using an ICS and provided greater improvements than CIC160 q.d.
PMID: 19549432
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Amin A,Spyropoulos AC,Dobesh P,Shorr A,Hussein M,Mozaffari E,Benner JS
Department of Medicine, University of California Irvine, Irvine, CA, USA, anamin@uci.edu.
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Are hospitals delivering appropriate VTE prevention? The venous thromboembolism study to assess the rate of thromboprophylaxis (VTE start).
J Thromb Thrombolysis. 2009 Jun 23;:
The 7th conference of the American College of Chest Physicians (ACCP7) provides recommendations on the type, dose, and duration of thromboprophylaxis in hospitalized patients at risk of venous thromboembolism (VTE), but the extent to which hospitals follow these criteria has not been well studied. Discharge and billing records for patients admitted to any of 16 acute-care hospitals from January 2005 to December 2006 were obtained. Patients 18 years or older who had an inpatient stay >/=2 days and no apparent contraindications for thromboprophylaxis were grouped into the categories of critical care, surgery and medically ill before being assessed for additional VTE risk factors based on the diagnostic criteria outlined in ACCP7. For patients at risk, the recommended type (mechanical or pharmacologic), dose, and duration of thromboprophylaxis was identified based on the guidelines and compared to the regimen actually received, if any. Among the 258,556 hospitalized patients, 68,278 (26.4%) were determined to be at risk of VTE without apparent contraindications for thromboprophylaxis. The proportions of patients who received the appropriate type, dose, and duration of thromboprophylaxis were 10.5, 9.8, and 17.9% for critical care, medical, and surgical patients, respectively. Of those at risk, 36.8% received no thromboprophylaxis and an additional 50.2% received thromboprophylaxis deemed inappropriate for one or more reasons. The implementation of ACCP7 guidelines for type, dosage, and duration of thromboprophylaxis is low in patients at risk of VTE. There is a need for physicians and health systems to improve awareness and implementation of recommended thromboprophylaxis.
PMID: 19548071
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Zell JA,Tsang WY,Taylor TH,Mehta RS,Anton-Culver H
Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California-Irvine, Irvine, CA 92697, USA. jzell@uci.edu
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Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry.
Breast Cancer Res. 2009;11(1):R9
INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer associated with overexpression of Her2/Neu (human epidermal growth factor-like receptor 2 (HER2)) and poor survival. We investigated survival differences for IBC patient cases based on hormone receptor status and HER2 receptor status using data from the California Cancer Registry, as contrasted with locally advanced breast cancer (LABC), metastatic breast cancer (MBC) and non-T4 breast cancer. METHODS: A case-only analysis of 80,099 incident female breast cancer patient cases in the California Cancer Registry during 1999 to 2003 was performed, with follow-up through March 2007. Overall survival (OS) and breast cancer-specific survival (BC-SS) were analyzed using Kaplan-Meier methods and Cox proportional hazards ratios. RESULTS: A total of 2,014 IBC, 1,268 LABC, 3,059 MBC, and 73,758 non-T4 breast cancer patient cases were identified. HER2+ was associated with advanced tumor stage (P < 0.0001). IBC patient cases were more likely to be HER2+ (40%) and less likely to be hormone receptor-positive (HmR+) (59%) compared with LABC (35% and 69%, respectively), MBC (35% and 74%), and non-T4 patient cases (22% and 82%). HmR+ status was associated with improved OS and BC-SS for each breast cancer subtype after adjustment for clinically relevant factors. In multivariate analysis, HER2+ (versus HER2-) status was associated with poor BC-SS for non-T4 patient cases (hazards ratio = 1.16, 95% confidence interval 1.05 to 1.28) and had a borderline significant association with improved BC-SS for IBC (hazards ratio = 0.82, 95% confidence interval = 0.68 to 0.99). CONCLUSIONS: Despite an association with advanced tumor stage, HER2+ status is not an independent adverse prognostic factor for survival among IBC patient cases.
PMID: 19228416
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Berg J,Brecht ML,Morphew T,Tichacek MJ,Chowdhury Y,Galant S
Program in Nursing Science, The University of California, Irvine, CA 92697, USA. jpberg@uci.edu
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Identifying preschool children with asthma in Orange County.
J Asthma. 2009 Jun;46(5):460-4
Airway changes related to childhood asthma occur early in the disease process. This pilot study focuses on the validation of the Breathmobile Case Identification Survey (BCIS) in preschool-age children in Orange County, CA. Fifty-two children from low-income Spanish-speaking families participated in the study. Thirteen children were identified as possibly having asthma from the survey results compared with 20 children diagnosed by an asthma specialist. We found that the complete seven-question survey had a sensitivity of 0.65 and a specificity of 0.94. An abbreviated three-question version had a sensitivity of 0.70 and a specificity of 0.84. Our data suggest that the abbreviated BCIS, which is simple and easily analyzed, may be a useful tool in identifying young children who are at risk for asthma and need further evaluation and appropriate therapy.
PMID: 19544165
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Randhawa I,Chin T,Nussbaum E
UC Irvine Department of Pediatrics, Miller Children's Hospital, 2801 Atlantic Ave., Long Beach, California 90806, USA. docrandhawa@yahoo.com
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Resolution of corticosteroid-induced diabetes in allergic bronchopulmonary aspergillosis with omalizumab therapy: a novel approach.
J Asthma. 2009 Jun;46(5):445-7
PMID: 19544162
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Kaplan AG,Kolla SB,Gamboa AJ,Box GN,Louie MK,Andrade L,Santos RT,Gan JM,Moskowitz RM,Shell C,Gustin W,Clayman RV,McDougall EM
Department of Urology, University of California Irvine, Orange, California 92868-3298, USA.
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Preliminary evaluation of a genitourinary skills training curriculum for medical students.
J Urol. 2009 Aug;182(2):668-73
PURPOSE: Basic urology training in medical school is considered important for many medical and surgical disciplines. We developed a 2-day intensive genitourinary skills training curriculum for medical students beginning their clinical clerkship training years and evaluated the initial experience with this program. MATERIALS AND METHODS: All 94 third-year medical students at the University of California, Irvine were required to participate in a 5.5-hour genitourinary examination skills training program. The teaching course included 1.5 hours of didactic lecture and video presentation with questions and answers, followed by 5, 45-minute hands-on stations including male Foley catheter placement, female Foley catheter placement, testicular examination and digital rectal examination training with a standardized patient, virtual reality cystourethroscopy and, lastly, a urologist led tutorial of abnormal genitourinary findings. The students completed questionnaires before and after the course concerning their experience. At the end of the course the students rated the usefulness of each part of the curriculum and evaluated the faculty. In addition, they were required to complete a multiple choice examination that included 4 genitourinary specific questions. RESULTS: All 94 medical students completed the genitourinary skills training course. Before the course less than 10% of students reported comfort with genitourinary skills, including testicular examination (5%), digital rectal examination (10%), male Foley catheter placement and female Foley catheter placement (2%). Following the course the comfort level improved in all parameters of digital rectal examination (100%) and testicular examination, male Foley catheter placement and female Foley catheter placement (98%). The students rated in the order of most to least useful training 1) standardized patient for testicular examination and digital rectal examination teaching, 2) male Foley catheter placement and female Foley catheter placement training, 3) didactic lecture, 4) tutorial of abnormal genitourinary examination findings and 5) virtual reality cystourethroscopy. On the examination questions following the course 80% to 98% of the class answered each urology content question correctly. CONCLUSIONS: An intensive skills training curriculum significantly improved medical student comfort and knowledge with regard to basic genitourinary skills including testicular examination, rectal examination, and Foley catheter placement in the male and female patient. Further followup will be performed to determine the application of these skills during clinical clerkship rotations.
PMID: 19539310
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Halpern AR,Nishi N,Wen J,Yang F,Xiang C,Penner RM,Corn RM
Department of Chemistry, University of California-Irvine, Irvine, California 92697, USA.
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Characterization of electrodeposited gold and palladium nanowire gratings with optical diffraction measurements.
Anal Chem. 2009 Jul 15;81(14):5585-92
Parallel arrays of either Au or Pd nanowires were fabricated on glass substrates via the electrochemical process of lithographically patterned nanowire electrodeposition (LPNE) and then characterized with scanning electron microscopy (SEM) and a series of optical diffraction measurements at 633 nm. Nanowires with widths varying from 25 to 150 nm were electrodeposited onto nanoscale Ni surfaces created by the undercut etching of a photoresist pattern on a planar substrate. With the use of a simple transmission grating geometry, up to 60 diffraction orders were observed from the nanowire gratings, with separate oscillatory intensity patterns appearing in the even and odd diffraction orders. The presence of these intensity oscillations is attributed to the LPNE array fabrication process, which creates arrays with alternating interwire spacings of distances d +Delta and d -Delta, where d = 25 microm and the asymmetry Delta varied from 0 to 3.5 microm. The amount of asymmetry could be controlled by varying the LPNE undercut etching time during the creation of the nanoscale Ni surfaces. The Fourier transform of a mathematical model of the nanowire array was used to predict the diffraction intensity patterns and quantitatively determine Delta for any grating. Additional sensitivity and an expanded diffraction order range were obtained through the use of external reflection (ER) and total internal reflection (TIR) diffraction geometries.
PMID: 19537714
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Pohl N,Sison-Mangus MP,Yee EN,Liswi SW,Briscoe AD
Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA. npohl@uci.edu
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Impact of duplicate gene copies on phylogenetic analysis and divergence time estimates in butterflies.
BMC Evol Biol. 2009;9:99
BACKGROUND: The increase in availability of genomic sequences for a wide range of organisms has revealed gene duplication to be a relatively common event. Encounters with duplicate gene copies have consequently become almost inevitable in the context of collecting gene sequences for inferring species trees. Here we examine the effect of incorporating duplicate gene copies evolving at different rates on tree reconstruction and time estimation of recent and deep divergences in butterflies. RESULTS: Sequences from ultraviolet-sensitive (UVRh), blue-sensitive (BRh), and long-wavelength sensitive (LWRh) opsins,EF-1 and COI were obtained from 27 taxa representing the five major butterfly families (5535 bp total). Both BRh and LWRh are present in multiple copies in some butterfly lineages and the different copies evolve at different rates. Regardless of the phylogenetic reconstruction method used, we found that analyses of combined data sets using either slower or faster evolving copies of duplicate genes resulted in a single topology in agreement with our current understanding of butterfly family relationships based on morphology and molecules. Interestingly, individual analyses of BRh and LWRh sequences also recovered these family-level relationships. Two different relaxed clock methods resulted in similar divergence time estimates at the shallower nodes in the tree, regardless of whether faster or slower evolving copies were used, with larger discrepancies observed at deeper nodes in the phylogeny. The time of divergence between the monarch butterfly Danaus plexippus and the queen D. gilippus (15.3-35.6 Mya) was found to be much older than the time of divergence between monarch co-mimic Limenitis archippus and red-spotted purple L. arthemis (4.7-13.6 Mya), and overlapping with the time of divergence of the co-mimetic passionflower butterflies Heliconius erato and H. melpomene (13.5-26.1 Mya). Our family-level results are congruent with recent estimates found in the literature and indicate an age of 84-113 million years for the divergence of all butterfly families. CONCLUSION: These results are consistent with diversification of the butterfly families following the radiation of angiosperms and suggest that some classes of opsin genes may be usefully employed for both phylogenetic reconstruction and divergence time estimation.
PMID: 19439087
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Johnson BA,Xu Z,Ali SS,Leon M
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697-4550, USA. bajohnso@uci.edu
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Spatial representations of odorants in olfactory bulbs of rats and mice: similarities and differences in chemotopic organization.
J Comp Neurol. 2009 Jun 20;514(6):658-73
In previous studies, we mapped glomerular layer 2-deoxyglucose uptake evoked by hundreds of both systematically related and chemically distinct odorants in rat olfactory bulbs. To determine which principles of chemotopic organization revealed in these studies may be more fundamental and which may be more species typical, we now have characterized patterns of responses to 30 of these odorants in mice. We found that only a few odorants evoked their multiple foci of peak activity in exactly the same locations in the two species. In mice, as in rats, odorants that shared molecular features evoked overlapping patterns, but the locations of the feature-responsive domains often differed in rats and mice. In rats, increasing carbon number within a homologous series of aliphatic odorants is generally associated with rostral and ventral progressions of activity within domains responding to odorant functional group and/or hydrocarbon backbone. Such chemotopic progressions were not obvious in mice, which instead showed more abrupt differences in activated glomeruli within the domains for odorants differing by a single methylene group. Despite the differences, quantitative relationships between overall uptake patterns exhibited a similar organization with respect to odorant chemistry for the two species, probably as a result of partial overlaps of peak domains and more extensive overlaps in large, low-activity areas for rats and mice. We conclude that clustering responses to shared odorant features may be a general strategy for odor coding but that the specific locations of high-activity domains may be unique to a species.
PMID: 19363812
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Minckler DS,Hill RA
University of California Irvine, Department of Ophthalmology, Irvine, CA 92697-4375, USA. minckler@uci.edu
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Use of novel devices for control of intraocular pressure.
Exp Eye Res. 2009 Apr;88(4):792-8
This brief review in honor of Douglas Johnson, MD describes the rationales and initial clinical outcomes in studies to date on Trabectome, Glaukos iStent, iScience (canaloplasty), and Solx (suprachoroidal shunt), all newly developed surgical technologies for treatment of open-angle glaucomas. These new approaches to angle surgery have been demonstrated in preliminary case series to safely lower IOP in the mid-teens with far fewer complications than expected with trabeculectomy and without anti-fibrotics. Trabectome and iStent are relatively non-invasive, aim to improve access of aqueous to collector channels and do not preclude subsequent standard surgery. Canaloplasty, modified from viscocanalostomy, is thought to improve trans-trabecular flow. Solx potentially offers an adjustable aqueous outflow into the suprachoroidal space.
PMID: 19154735
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Moskowitz RM,Young JL,Box GN,Paré LS,Clayman RV
Department of Urology, University of California, Irvine, Irvine, California, USA. Rmoskowi@uci.edu
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Retroperitoneal transdiaphragmatic robotic-assisted laparoscopic resection of a left thoracolumbar neurofibroma.
JSLS. 13(1):64-8
OBJECTIVE: Robotic technology has been used in a variety of surgical procedures for its 3D magnification and precision. Minimally invasive techniques have already become common in neurosurgery; however, robotic-assisted procedures in neurosurgery are still a relatively new frontier. This report describes the first use of robotic technology to resect a left thoracolumbar neurofibroma. CASE REPORT: A 19-year-old male with a family history of neurofibromatosis was diagnosed with a suspected 3-cm x 4-cm neurofibroma in the T12-L1 left paraspinal area. His only complaint was back pain requiring narcotic analgesics. He had no other findings on physical examination or laboratory/radiologic workup. METHODS: After consulting urologic robotic surgeons, it was agreed to use the da Vinci robot (Intuitive Surgical, Sunnyvale, CA) for the resection of this mass. Following retroperitoneal laparoscopic access, the urologic surgeons opened the diaphragm and began the initial mobilization of the mass laparoscopically. The robot was docked, and the neurosurgeon operated the robot at the console to resect the mass from its nerve origin. There were no complications, and the mass, a confirmed neurofibroma, was completely removed. The patient was discharged on postoperative day 2; his back pain resolved, requiring no analgesia by the end of the first postoperative week. CONCLUSION: This case provides early evidence that robotic assistance can be successfully used for the resection of a paraspinal neurofibroma.
PMID: 19366544
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Swamidass SJ,Azencott CA,Lin TW,Gramajo H,Tsai SC,Baldi P
School of Information and Computer Sciences, Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, California 92697-3435, USA. sswamida@ics.uci.edu
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Influence relevance voting: an accurate and interpretable virtual high throughput screening method.
J Chem Inf Model. 2009 Apr;49(4):756-66
Given activity training data from high-throughput screening (HTS) experiments, virtual high-throughput screening (vHTS) methods aim to predict in silico the activity of untested chemicals. We present a novel method, the Influence Relevance Voter (IRV), specifically tailored for the vHTS task. The IRV is a low-parameter neural network which refines a k-nearest neighbor classifier by nonlinearly combining the influences of a chemical's neighbors in the training set. Influences are decomposed, also nonlinearly, into a relevance component and a vote component. The IRV is benchmarked using the data and rules of two large, open, competitions, and its performance compared to the performance of other participating methods, as well as of an in-house support vector machine (SVM) method. On these benchmark data sets, IRV achieves state-of-the-art results, comparable to the SVM in one case, and significantly better than the SVM in the other, retrieving three times as many actives in the top 1% of its prediction-sorted list. The IRV presents several other important advantages over SVMs and other methods: (1) the output predictions have a probabilistic semantic; (2) the underlying inferences are interpretable; (3) the training time is very short, on the order of minutes even for very large data sets; (4) the risk of overfitting is minimal, due to the small number of free parameters; and (5) additional information can easily be incorporated into the IRV architecture. Combined with its performance, these qualities make the IRV particularly well suited for vHTS.
PMID: 19391629
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Saremi F,Gurudevan SV,Harrison AT
Department of Radiological Sciences, Division of Cardiothoracic Imaging, University of California, Irvine, Orange, CA 92868, USA. fsaremi@uci.edu
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Isolated right ventricular infarction owing to anomalous origin of right coronary artery: role of MR and CT in diagnosis.
J Thorac Imaging. 2009 Feb;24(1):34-7
Our case report describes a very rare example of isolated right ventricular infarction in a 39-year-old patient with nondominant anomalous right coronary artery. We took advantage of both computed tomography and magnetic resonance imaging techniques to diagnose this case. The computed tomography scan characterized the anatomy and course of the right coronary artery and cardiac magnetic resonance imaging distinguished the area of infarction to the right ventricles.
PMID: 19242301
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Katz MH,Wang H,Fleming JB,Sun CC,Hwang RF,Wolff RA,Varadhachary G,Abbruzzese JL,Crane CH,Krishnan S,Vauthey JN,Abdalla EK,Lee JE,Pisters PW,Evans DB
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. katzmh@uci.edu
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Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma.
Ann Surg Oncol. 2009 Apr;16(4):836-47
INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy. METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed. RESULTS: Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival. CONCLUSIONS: Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy.
PMID: 19194760
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