Rajan PV,Chung JH,Porto M,Wing DA
Department of Obstetrics and Gynecology, University of California, Irvine, Orange, California 92868, USA. mfm@uci.edu
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Correlation of increased fetal asymmetry with shoulder dystocia in the nondiabetic woman with suspected macrosomia.
J Reprod Med. 2009 Aug;54(8):478-82
OBJECTIVE: To determine if the sonographic difference of > or = 2.6 cm between the fetal abdominal diameter (AD) and biparietal diameter (BPD), a proxy for fetal asymmetry, has an association with shoulder dystocia in nondiabetic women with suspected macrosomia. STUDY DESIGN: A retrospective cohort study was performed in 3 Southern California tertiary care hospitals. We identified patients in whom sonographic evaluation after 36 weeks' gestation demonstrated an estimated fetal weight > 4,000 g. Additional prenatal and delivery information was obtained from hospital records. RESULTS: We identified 159 subjects who met ultrasound criteria and underwent a vaginal delivery. The mean AD-BPD difference in the shoulder dystocia group was significantly greater than in the group without shoulder dystocia (2.76 +/- 0.59 vs. 2.37 +/- 0.56, p = 0.001). The adjusted OR of shoulder dystocia in the group with an AD-BPD difference > or = 2.6 was 3.67 (95% CI, 1.44-9.36). CONCLUSION: Significant discordance between the fetal head and abdomen appears to be associated with an increased rate of shoulder dystocia in a nondiabetic population with suspected macrosomia.
PMID: 19769192
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Colt H,Murgu SD,Ahn YC,Brenner M
University of California School of Medicine, Pulmonary and Critical Care Medicine, Department of Medicine, 101 the City Drive South, Building 53, Room 119, Route 81 Orange, California 92868, USA. hcolt@uci.edu
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Multimodality bronchoscopic imaging of tracheopathica osteochondroplastica.
J Biomed Opt. 14(3):034035
Results of a commercial optical coherence tomography system used as part of a multimodality diagnostic bronchoscopy platform are presented for a 61-year-old patient with central airway obstruction from tracheopathica osteochondroplastica. Comparison to results of white-light bronchoscopy, histology, and endobronchial ultrasound examination are accompanied by a discussion of resolution, penetration depth, contrast, and field of view of these imaging modalities. White-light bronchoscopy revealed irregularly shaped, firm submucosal nodules along cartilaginous structures of the anterior and lateral walls of the trachea, sparing the muscular posterior membrane. Endobronchial ultrasound showed a hyperechoic density of 0.4 cm thickness. optical coherence tomography (OCT) was performed using a commercially available, compact time-domain OCT system (Niris System, Imalux Corp., Cleveland, Ohio) with a magnetically actuating probe (two-dimensional, front imaging, and inside actuation). Images showed epithelium, upper submucosa, and osseous submucosal nodule layers corresponding with histopathology. To our knowledge, this is the first time these commercially available systems are used as part of a multimodality bronchoscopy platform to study diagnostic imaging of a benign disease causing central airway obstruction. Further studies are needed to optimize these systems for pulmonary applications and to determine how new-generation imaging modalities will be integrated into a multimodality bronchoscopy platform.
PMID: 19566328
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Kravitz BA,Corrada MM,Kawas CH
Department of Neurobiology and Behavior, University of California at Irvine, Irvine, CA, USA. bkravitz@uci.edu
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Elevated C-reactive protein levels are associated with prevalent dementia in the oldest-old.
Alzheimers Dement. 2009 Jul;5(4):318-23
BACKGROUND: C-reactive protein (CRP) is a nonspecific marker of inflammation that is increased in the brain and serum of patients with Alzheimer's disease (AD), and has been associated with increased risk of developing dementia. Inflammation increases with age, and the number of people reaching age 90 years and older is growing, making the association between inflammation and dementia increasingly relevant. Using a cross-sectional design, we examined whether high levels of serum CRP are associated with increased odds of prevalent dementia in the oldest-old. METHODS: Serum CRP levels of 305 participants (mean age +/- standard deviation, 94.3 +/- 2.9 years) from the 90+ Study, a longitudinal cohort study of people aged 90 years and older, were evaluated with respect to all-cause dementia. Levels of CRP were divided into three categories: undetectable (<0.5 mg/dL), detectable (0.5-0.7 mg/dL), and elevated (> or =0.8 mg/dL). Odds ratios (ORs) were calculated using logistic regression, and were adjusted for covariates. RESULTS: Relative to participants with undetectable CRP levels, participants with detectable or elevated CRP levels had increased odds of all-cause dementia (detectable: OR, 3.0; 95% confidence interval, 1.2-7.3; elevated: OR, 5.0; 95% confidence interval, 1.9-12.9). When participants were subdivided by gender, significantly increased ORs were seen only in women. CONCLUSIONS: In the oldest-old, high CRP levels are associated with increased odds of all-cause dementia, particularly in women. Prospective studies are necessary to confirm whether increased CRP levels are associated with an increased risk of developing dementia in this age group.
PMID: 19560102
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Cramer SC,Dobkin BH,Noser EA,Rodriguez RW,Enney LA
Department of Neurology, University of California, Irvine, USA. scramer@uci.edu
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Randomized, placebo-controlled, double-blind study of ropinirole in chronic stroke.
Stroke. 2009 Sep;40(9):3034-8
BACKGROUND AND PURPOSE: Evidence suggests the potential to improve motor status in patients with stroke by modifying brain catecholaminergic tone. The current study hypothesized that increased dopaminergic tone via the dopamine agonist ropinirole, when combined with physiotherapy (PT), would significantly and safely increase gait velocity. METHODS: Patients with moderate motor deficits due to stroke 1 to 12 months prior were randomized (double blinded) to 9 weeks of immediate-release ropinirole or placebo, each with PT, and followed up for 3 additional weeks. Drug dose (0.25 to 4 mg once daily) was titrated weekly, as tolerated. The primary end point was gait velocity during the 12 weeks of study participation. RESULTS: Patients in the ropinirole+PT group averaged 2.4 mg/d by end of week 9, although the target dose was at least 3 mg/d. Ropinirole+PT was generally safe and well tolerated, including no drug-related serious adverse events. Across all 33 enrollees, significant gains were found over time for gait velocity and for most secondary end points. However, gains did not differ by treatment assignment. PT and occupational therapy were commonly prescribed outside of the trial, although the extent of these was not correlated with study outcomes. CONCLUSIONS: At doses achieved in this trial, increased dopaminergic tone via ropinirole+PT was generally well tolerated but did not show any improvement over and above the effects of PT alone.
PMID: 19520987
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Ayala FJ
University of California, Irvine, CA 92697, USA. fjayala@uci.edu
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One hundred fifty years without Darwin are enough!
Genome Res. 2009 May;19(5):693-9
PMID: 19411593
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Felgner PL,Kayala MA,Vigil A,Burk C,Nakajima-Sasaki R,Pablo J,Molina DM,Hirst S,Chew JS,Wang D,Tan G,Duffield M,Yang R,Neel J,Chantratita N,Bancroft G,Lertmemongkolchai G,Davies DH,Baldi P,Peacock S,Titball RW
Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA. pfelgner@uci.edu
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A Burkholderia pseudomallei protein microarray reveals serodiagnostic and cross-reactive antigens.
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13499-504
Understanding the way in which the immune system responds to infection is central to the development of vaccines and many diagnostics. To provide insight into this area, we fabricated a protein microarray containing 1,205 Burkholderia pseudomallei proteins, probed it with 88 melioidosis patient sera, and identified 170 reactive antigens. This subset of antigens was printed on a smaller array and probed with a collection of 747 individual sera derived from 10 patient groups including melioidosis patients from Northeast Thailand and Singapore, patients with different infections, healthy individuals from the USA, and from endemic and nonendemic regions of Thailand. We identified 49 antigens that are significantly more reactive in melioidosis patients than healthy people and patients with other types of bacterial infections. We also identified 59 cross-reactive antigens that are equally reactive among all groups, including healthy controls from the USA. Using these results we were able to devise a test that can classify melioidosis positive and negative individuals with sensitivity and specificity of 95% and 83%, respectively, a significant improvement over currently available diagnostic assays. Half of the reactive antigens contained a predicted signal peptide sequence and were classified as outer membrane, surface structures or secreted molecules, and an additional 20% were associated with pathogenicity, adaptation or chaperones. These results show that microarrays allow a more comprehensive analysis of the immune response on an antigen-specific, patient-specific, and population-specific basis, can identify serodiagnostic antigens, and contribute to a more detailed understanding of immunogenicity to this pathogen.
PMID: 19666533
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Romero Rosales K,Peralta ER,Guenther GG,Wong SY,Edinger AL
Department of Developmental and Cell Biology, University of California-Irvine, Irvine, CA 92697-2300, USA.
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Rab7 activation by growth factor withdrawal contributes to the induction of apoptosis.
Mol Biol Cell. 2009 Jun;20(12):2831-40
The Rab7 GTPase promotes membrane fusion reactions between late endosomes and lysosomes. In previous studies, we demonstrated that Rab7 inactivation blocks growth factor withdrawal-induced cell death. These results led us to hypothesize that growth factor withdrawal activates Rab7. Here, we show that growth factor deprivation increased both the fraction of Rab7 that was associated with cellular membranes and the percentage of Rab7 bound to guanosine triphosphate (GTP). Moreover, expressing a constitutively GTP-bound mutant of Rab7, Rab7-Q67L, was sufficient to trigger cell death even in the presence of growth factors. This activated Rab7 mutant was also able to reverse the growth factor-independent cell survival conferred by protein kinase C (PKC) delta inhibition. PKCdelta is one of the most highly induced proteins after growth factor withdrawal and contributes to the induction of apoptosis. To evaluate whether PKCdelta regulates Rab7, we first examined lysosomal morphology in cells with reduced PKCdelta activity. Consistent with a potential role as a Rab7 activator, blocking PKCdelta function caused profound lysosomal fragmentation comparable to that observed when Rab7 was directly inhibited. Interestingly, PKCdelta inhibition fragmented the lysosome without decreasing Rab7-GTP levels. Taken together, these results suggest that Rab7 activation by growth factor withdrawal contributes to the induction of apoptosis and that Rab7-dependent fusion reactions may be targeted by signaling pathways that limit growth factor-independent cell survival.
PMID: 19386765
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Astarita G,Ahmed F,Piomelli D
Department of Pharmacology, University of California - Irvine, Irvine, CA, USA.
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Lipidomic analysis of biological samples by liquid chromatography coupled to mass spectrometry.
Methods Mol Biol. 2009;579:201-19
Lipidomics studies the large-scale changes in nonwater-soluble metabolites (lipids) accompanying perturbations of biological systems. Because lipids are involved in crucial biological mechanisms, there is a growing scientific interest in using lipidomic approaches to understand the regulation of the lipid meta-bolism in all eukaryotic and prokaryotic organisms. Lipidomics is a powerful tool in system biology that can be used together with genomics, transcriptomics, and proteomics to answer biological questions arising from various scientific areas such as environmental sciences, pharmacology, nutrition, biophysics, cell biology, physiology, pathology, and disease diagnostics. One of the main challenges for lipidomic analysis is the range of concentrations and chemical complexity of different lipid species. In this chapter, we present a lipidomic approach that combines sample preparation, chromatographic, and intrasource ionization separation coupled to mass spectrometry for analyzing a broad-range of lipid molecules in biological samples.
PMID: 19763477
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Kawauchi S,Calof AL,Santos R,Lopez-Burks ME,Young CM,Hoang MP,Chua A,Lao T,Lechner MS,Daniel JA,Nussenzweig A,Kitzes L,Yokomori K,Hallgrimsson B,Lander AD
Department of Anatomy and Neurobiology, University of California Irvine, Irvine, California, United States of America.
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Multiple organ system defects and transcriptional dysregulation in the nipbl mouse, a model of cornelia de lange syndrome.
PLoS Genet. 2009 Sep;5(9):e1000650
Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75-80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only approximately 30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/- mice and in individuals with CdLS.
PMID: 19763162
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Jeter PE,Dosher BA,Petrov A,Lu ZL
Memory Attention Perception (MAP) Laboratory, Department of Cognitive Sciences, UC Irvine, Irvine, CA, USA. pjeter@uci.edu.
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Task precision at transfer determines specificity of perceptual learning.
J Vis. 2009;9(3):1.1-13
Perceptual learning, the improvement in performance with practice, reflects plasticity in the adult visual system. We challenge a standard claim that specificity of perceptual learning depends on task difficulty during training, instead showing that specificity, or conversely transfer, is primarily controlled by the precision demands (i.e., orientation difference) of the transfer task. Thus, for an orientation discrimination task, transfer of performance improvement is observed in low-precision transfer tasks, while specificity of performance improvement is observed in high-precision transfer tasks, regardless of the precision of initial training. The nature of specificity places important constraints on mechanisms of transfer in visual learning. These results contribute to understanding generalization of practiced improvements that may be key to the development of expertise and for applications in remediation.
PMID: 19757940
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Saremi F,Knoll AN,Bendavid OJ,Schultze-Haakh H,Narula N,Sarlati F
Department of Radiological Sciences, Division of Body Imaging, University of California-Irvine, UCI Medical Center, 101 The City Drive, Route 140, Orange, CA 92868-3298, USA. fsaremi@uci.edu
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Characterization of genitourinary lesions with diffusion-weighted imaging.
Radiographics. 29(5):1295-317
Diffusion-weighted imaging has been widely accepted as a powerful imaging technique in neuroradiology. Until recently, the inclusion of diffusion-weighted sequences in body imaging protocols has been hindered by technical limitations. However, with advances in magnetic resonance (MR) imaging technology and technique, these limitations are being overcome. The addition of diffusion-weighted sequences to routine abdominopelvic MR imaging protocols has been found to yield diagnostically useful information with only a minimal increase in imaging time. More specifically, the use of diffusion-weighted imaging in the genitourinary system can facilitate the detection and characterization of genitourinary tract lesions that demonstrate equivocal signal intensity characteristics with routine MR imaging sequences. Diffusion-weighted imaging is not only helpful in differentiating benign from malignant processes, but it can also be used to assess meta-static lesions, possible tumor recurrence, and treatment response. Because it does not require injection of a gadolinium-based contrast agent, diffusion-weighted imaging can be used in patients with renal insufficiency or contrast material allergy. Most of the body diffusion-weighted imaging studies reported in the literature to date have been conducted with 1.5-T magnets. However, the feasibility of body diffusion-weighted imaging at 3.0 T is currently under investigation in an effort to determine the efficacy of the routine inclusion of diffusion-weighted imaging sequences in 3.0-T body MR imaging protocols.
PMID: 19755597
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Cahalan MD,Chandy KG
Department of Physiology and Biophysics, and the Institute for Immunology, University of California, Irvine, Irvine, CA 92697-4561, USA. mcahalan@uci.edu
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The functional network of ion channels in T lymphocytes.
Immunol Rev. 2009 Sep;231(1):59-87
For more than 25 years, it has been widely appreciated that Ca2+ influx is essential to trigger T-lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers and genetic manipulation have shown that a unique contingent of ion channels orchestrates the initiation, intensity, and duration of the Ca2+ signal. Five distinct types of ion channels--Kv1.3, KCa3.1, Orai1+ stromal interacting molecule 1 (STIM1) [Ca2+-release activating Ca2+ (CRAC) channel], TRPM7, and Cl(swell)--comprise a network that performs functions vital for ongoing cellular homeostasis and for T-cell activation, offering potential targets for immunomodulation. Most recently, the roles of STIM1 and Orai1 have been revealed in triggering and forming the CRAC channel following T-cell receptor engagement. Kv1.3, KCa3.1, STIM1, and Orai1 have been found to cluster at the immunological synapse following contact with an antigen-presenting cell; we discuss how channels at the synapse might function to modulate local signaling. Immuno-imaging approaches are beginning to shed light on ion channel function in vivo. Importantly, the expression pattern of Ca2+ and K+ channels and hence the functional network can adapt depending upon the state of differentiation and activation, and this allows for different stages of an immune response to be targeted specifically.
PMID: 19754890
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Hoshino Y,Urakami T,Kodama T,Koide H,Oku N,Okahata Y,Shea KJ
Department of Chemistry, University of California, Irvine, Irvine, CA 92697, USA. yhoshino@uci.edu
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Design of synthetic polymer nanoparticles that capture and neutralize a toxic peptide.
Small. 2009 Jul;5(13):1562-8
Designed polymer nanoparticles (NPs) capable of binding and neutralizing a biomacromolecular toxin are prepared. A library of copolymer NPs is synthesized from combinations of functional monomers. The binding capacity and affinity of the NPs are individually analyzed. NPs with optimized composition are capable of neutralizing the toxin even in a complex biological milieu. It is anticipated that this strategy will be a starting point for the design of synthetic alternatives to antibodies.
PMID: 19296557
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Arold SP,Malavia N,George SC
Department of Biomedical Engineering, University of California, Irvine, USA. scgeorge@uci.edu
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Mechanical compression attenuates normal human bronchial epithelial wound healing.
Respir Res. 2009;10:9
BACKGROUND: Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. METHODS: Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1) unperturbed control cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH2O), and 4) 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. RESULTS: We found that mechanical compression and scrape injury increase TGF-beta2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. CONCLUSION: Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.
PMID: 19171062
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Kahn CA,Schultz CH,Miller KT,Anderson CL
Department of Emergency Medicine, University of California, Irvine, Orange, CA 92868, USA. ckahn@uci.edu
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Does START triage work? An outcomes assessment after a disaster.
Ann Emerg Med. 2009 Sep;54(3):424-30, 430.e1
STUDY OBJECTIVE: The mass casualty triage system known as simple triage and rapid treatment (START) has been widely used in the United States since the 1980s. However, no outcomes assessment has been conducted after a disaster to determine whether assigned triage levels match patients' actual clinical status. Researchers hypothesize that START achieves at least 90% sensitivity and specificity for each triage level and ensures that the most critical patients are transported first to area hospitals. METHODS: The performance of START was evaluated at a train crash disaster in 2003. Patient field triage categories and scene times were obtained from county reports. Patient medical records were then reviewed at all receiving hospitals. Victim arrival times were obtained and correct triage categories determined a priori using a combination of the modified Baxt criteria and hospital admission. Field and outcomes-based triage categories were compared, defining the appropriateness of each triage assignment. RESULTS: Investigators reviewed 148 records at 14 receiving hospitals. Field triage designations comprised 22 red (immediate), 68 yellow (delayed), and 58 green (minor) patients. Outcomes-based designations found 2 red, 26 yellow, and 120 green patients. Seventy-nine patients were overtriaged, 3 were undertriaged, and 66 patients' outcomes matched their triage level. No triage level met both the 90% sensitivity and 90% specificity requirement set forth in the hypothesis, although red was 100% sensitive (95% confidence interval [CI] 16% to 100%) and green was 89.3% specific (95% CI 72% to 98%). The Obuchowski statistic was 0.81, meaning that victims from a higher-acuity outcome group had an 81% chance of assignment to a higher-acuity triage category. The median arrival time for red patients was more than 1 hour earlier than the other patients. CONCLUSION: This analysis demonstrates poor agreement between triage levels assigned by START at a train crash and a priori outcomes criteria for each level. START ensured acceptable levels of undertriage (100% red sensitivity and 89% green specificity) but incorporated a substantial amount of overtriage. START proved useful in prioritizing transport of the most critical patients to area hospitals first.
PMID: 19195739
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Odgers CL,Moffitt TE,Tach LM,Sampson A,Taylor RJ,Matthews CL,Caspi A
Department of Psychology and Social Behavior, University of California, Irvine, CA, 92697-7085, USA. codgers@uci.edu
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The protective effects of neighborhood collective efficacy on British children growing up in deprivation: a developmental analysis.
Dev Psychol. 2009 Jul;45(4):942-57
This article reports on the influence of neighborhood-level deprivation and collective efficacy on children's antisocial behavior between the ages of 5 and 10 years. Latent growth curve modeling was applied to characterize the developmental course of antisocial behavior among children in the E-Risk Longitudinal Twin Study, an epidemiological cohort of 2,232 children. Children in deprived versus affluent neighborhoods had higher levels of antisocial behavior at school entry (24.1 vs. 20.5, p < .001) and a slower rate of decline from involvement in antisocial behavior between the ages of 5 and 10 (-0.54 vs. -0.78, p < .01). Neighborhood collective efficacy was negatively associated with levels of antisocial behavior at school entry (r = -.10, p < .01) but only in deprived neighborhoods; this relationship held after controlling for neighborhood problems and family-level factors. Collective efficacy did not predict the rate of change in antisocial behavior between the ages of 5 and 10. Findings suggest that neighborhood collective efficacy may have a protective effect on children living in deprived contexts.
PMID: 19586172
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Baliraine FN,Afrane YA,Amenya DA,Bonizzoni M,Menge DM,Zhou G,Zhong D,Vardo-Zalik AM,Githeko AK,Yan G
Program in Public Health, College of Health Sciences, University of California at Irvine, Irvine, California 92697, USA. fbalirai@uci.edu
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High prevalence of asymptomatic plasmodium falciparum infections in a highland area of western Kenya: a cohort study.
J Infect Dis. 2009 Jul 1;200(1):66-74
BACKGROUND: Transmission of malaria in an area of hypoendemicity in the highlands of western Kenya is not expected to lead to rapid acquisition of immunity to malaria. However, the subpopulation of individuals with asymptomatic Plasmodium falciparum infection may play a significant role as an infection reservoir and should be considered in malaria-control programs. Determination of the spatiotemporal dynamics of asymptomatic subpopulations provides an opportunity to estimate the epidemiological importance of this group to malaria transmission. METHODS: Monthly parasitological surveys were undertaken for a cohort of 246 schoolchildren over 12 months. The prevalence of P. falciparum infection among 2,611 blood samples was analyzed by both microscopy and polymerase chain reaction, and infection durations were determined. RESULTS: Infection prevalence and duration (range, 1-12 months) decreased with age and altitude. The prevalence was high among pooled blood samples recovered from children aged 5-9 years (34.4%) and from those aged 10-14 years (34.1%) but was significantly lower among blood samples obtained from older children (9.1%). The prevalence decreased from 52.4% among pooled blood samples from children living at an altitude of approximately 1,430 m to 23.3% among pooled samples from children living at an altitude of 1,580 m. CONCLUSIONS: The prevalence of asymptomatic P. falciparum infection was high, with polymerase chain reaction analysis detecting a significantly greater number of infections, compared with microscopy. Our results are consistent with gradual acquisition of immunity with increasing age upon repeated infection, and they also show that the risk of malaria transmission is highly heterogeneous in the highland area. The results provide strong support for targeted malaria-control interventions.
PMID: 19476434
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Berger WE
Department of pediatrics, division of allergy and immunology, College of Medicine, University of California, Irvine, USA. wberger@uci.edu
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Acute bronchospasm from the patient's perspective.
Postgrad Med. 2005 Dec;118(6 Suppl Acute):44-7; discussion 48
Vast differences exist between the actions physicians report that they take and the patient's perception of those actions. Several patient satisfaction survey results are presented in this article. Many show that although patients are not often satisfied with their treatments or with the side effects they experience from medications, they are, in general, very satisfied with their physicians. These research studies point out that a very real "communications gap" exists between physicians and patients when examined from the patient's perspective.
PMID: 19667716
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Berger WE
Department of pediatrics, division of allergy and immunology, College of Medicine, University of California, Irvine, USA. weberger@uci.edu
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Treatment of acute bronchospasm in elderly patients.
Postgrad Med. 2005 Dec;118(6 Suppl Acute):34-7; discussion 38
Both asthma and chronic obstructive pulmonary disease (COPD) are often underdiagnosed and undertreated among the elderly. Patient compliance with treatments plans and medication schedules are often less than ideal. This paper presents results from clinical studies examining levalbuterol and racemic albuterol use among elderly patients who have asthma or COPD.
PMID: 19667714
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Berger WE
Department of pediatrics, division of allergy and immunology, College of Medicine, University of California, Irvine, USA. wberger@uci.edu
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Current options in the treatment of acute bronchospasm.
Postgrad Med. 2005 Dec;118(6 Suppl Acute):18-26
Asthma therapy has evolved significantly in the last 40 years from that used for primarily symptomatic relief to that which incorporates short-term relief agents, long-term preventive medications, and exacerbation relief products. Agents can now be prescribed for routine as well as emergency care. Continued development of medications are likely to offer patients better agents for control of their illness and mitigate occurrence of acute exacerbations. Better control allows for better patient health, reduced number of physician and emergency department visits, and reduced health care costs.
PMID: 19667712
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Berger WE,Cline DC
Department of pediatrics, division of allergy and immunology, College of Medicine, University of California, Irvine, USA. wberger@uci.edu
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Asthma and COPD: definitions, epidemiology, and treatment guidelines.
Postgrad Med. 2005 Dec;118(6 Suppl Acute):2-8
Asthma and chronic obstructive pulmonary disease (COPD) are disorders that affect millions of people in the United States and other countries in the world. Asthma is a chronic inflammatory disease of the airways that has cellular and molecular pathways. Affected patients have recurrent episodes of wheezing, dyspnea, chest tightness, and cough that can be treated to minimize impact. COPD is a disease that is characterized by airflow limitation that is not fully reversible. Prevalence of asthma may be leveling off. Prevalence of COPD is increasing, especially in women. Although several therapies are available, many patients do not seek treatment until COPD is moderately advanced.
PMID: 19667710
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Tanaka H,Yi TM
Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, USA.
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Synthetic morphology using alternative inputs.
PLoS One. 2009;4(9):e6946
Designing the shape and size of a cell is an interesting challenge for synthetic biology. Prolonged exposure to the mating pheromone alpha-factor induces an unusual morphology in yeast cells: multiple mating projections. The goal of this work was to reproduce the multiple projections phenotype in the absence of alpha-factor using a gain-of-function approach termed "Alternative Inputs (AIs)". An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. Interestingly, none of the alternative inputs were sufficient to produce multiple projections although some produced a single projection. Then, we extended our search by creating all combinations of alternative inputs and deletions that were summarized in an AIs-Deletions matrix. We found a genetic manipulation (AI-Ste5p ste2Delta) that enhanced the formation of multiple projections. Following up this lead, we demonstrated that AI-Ste4p and AI-Ste5p were sufficient to produce multiple projections when combined. Further, we showed that overexpression of a membrane-targeted form of Ste5p alone could also induce multiple projections. Thus, we successfully re-engineered the multiple projections mating morphology using alternative inputs without alpha-factor.
PMID: 19746161
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Fisk Z
Department of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697-4575, USA. zfisk@uci.edu
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Physics. The thermodynamics of quantum critical points.
Science. 2009 Sep 11;325(5946):1348-9
PMID: 19745139
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Yakob L,Yan G
Program in Public Health, University of California Irvine, Irvine, California, United States of America. lyakob@uci.edu
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Modeling the effects of integrating larval habitat source reduction and insecticide treated nets for malaria control.
PLoS One. 2009;4(9):e6921
Integrated vector management for malaria control has received a lot of recent interest. Attacking multiple points in the transmission cycle is hoped to act synergistically and improve upon current single-tool interventions based on the use of insecticide-treated bed nets (ITNs). In the present study, we theoretically examined the application of larval habitat source reduction with ITNs in reducing malaria transmission. We selected this type of environmental management to complement ITNs because of a potential secondary mode of action that both control strategies share. In addition to increasing vector mortality, ITNs reduce the rate at which female mosquitoes locate human hosts for blood feeding, thereby extending their gonotrophic cycle. Similarly, while reducing adult vector emergence and abundance, source reduction of larval habitats may prolong the cycle duration by extending delays in locating oviposition sites. We found, however, that source reduction of larval habitats only operates through this secondary mode of action when habitat density is below a critical threshold. Hence, we illustrate how this strategy becomes increasingly effective when larval habitats are limited. We also demonstrate that habitat source reduction is better suited to human populations of higher density and in the presence of insecticide resistance or when the insecticidal properties of ITNs are depleted.
PMID: 19742312
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Malinoski DJ,Hadjizacharia P,Salim A,Kim H,Dolich MO,Cinat M,Barrios C,Lekawa ME,Hoyt DB
Division of Trauma & Critical Care Surgery, UCI Medical Center, 333 City Boulevard West, Suite 705, Orange, CA 92868, USA. malinosd@uci.edu
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Elevated serum pancreatic enzyme levels after hemorrhagic shock predict organ failure and death.
J Trauma. 2009 Sep;67(3):445-9
BACKGROUND: Intraluminal pancreatic enzymes have been shown in animal models to be associated with multiple organ failure after hemorrhagic shock, independent of pancreatitis. The translocation of these enzymes into the circulation may serve as a marker of hemorrhagic shock-induced gut ischemia in critically injured trauma patients. We hypothesized that serum amylase and lipase would be significantly elevated in patients presenting in hemorrhagic shock and in those who develop organ failure. METHODS:: Review of a prospective database at a level-1 trauma center from 2000 to 2005. Two thousand seven hundred eleven critically injured trauma patients without pancreatic injuries were evaluated for shock (systolic pressure <90 mm Hg in the emergency department), massive transfusion (10 units of packed red blood cells within the first 24 hours), and organ failure (standard criteria for acute pulmonary, cardiovascular, renal, and hepatic system failure were used). Serum levels >2 times the upper limit of normal for amylase (30-130 U/L) and lipase (7-60 U/L) were defined as elevated. Univariate analyses were performed with the Pearson's chi, and binary logistic regression was used to determine significant risk factors for organ failure. Results with a p value <0.05 were considered significant and are reported. RESULTS:: Patients with elevated amylase (n = 481, 18%) were more likely to present in shock (16% vs. 8%), require massive transfusion (19% vs. 9%), develop organ failure (34% vs. 16%), and die (23% vs. 13%). Patients with elevated lipase (n = 288, 11%) were more likely to require massive transfusion (18% vs. 10%) and develop organ failure (43% vs. 16%). Independent predictors of organ failure were age (odds ratio [OR] = 1.016), Injury Severity Score (OR = 1.02), massive transfusion (OR = 3.1), elevated amylase (OR = 1.9), and elevated lipase (OR = 3.2). Elevated amylase was also an independent predictor of mortality (OR = 1.3). CONCLUSIONS:: Serum levels of pancreatic enzymes are elevated in patients who present in shock or require a massive transfusion and are independent predictors of organ failure. Whether these elevations are caused by ischemic pancreatitis or the translocation of intraluminal enteric pancreatic enzymes is uncertain and future studies are needed. Trauma patients with elevated pancreatic enzymes in the absence of a pancreatic injury have an increased risk of morbidity and mortality.
PMID: 19741384
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