Chen X,Aledia AS,Ghajar CM,Griffith CK,Putnam AJ,Hughes CC,George SC
Department of Biomedical Engineering, University of California Irvine, Irvine, California 92697-2715, USA.
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Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature.
Tissue Eng Part A. 2009 Jun;15(6):1363-71
One critical obstacle facing tissue engineering is the formation of functional vascular networks that can support tissue survival in vivo. We hypothesized that prevascularizing a tissue construct with networks of well-formed capillaries would accelerate functional anastomosis with the host upon implantation. Fibrin-based tissues were prevascularized with capillary networks by coculturing human umbilical vein endothelial cells (HUVECs) and fibroblasts in fibrin gels for 1 week. The prevascularized tissue and nonprevascularized controls were implanted subcutaneously onto the dorsal surface of immune-deficient mice and retrieved at days 3, 5, 7 and 14. HUVEC-lined vessels containing red blood cells were evident in the prevascularized tissue by day 5, significantly earlier than nonprevascularized tissues (14 days). Analysis of the HUVEC-lined vessels demonstrated that the number and area of perfused lumens in the prevascularized tissue were significantly larger compared to controls. In addition, collagen deposition and a larger number of proliferating cells were evident in the prevascularized tissue at day 14. Our results demonstrate that prevascularizing a fibrin-based tissue with well-formed capillaries accelerates anastomosis with the host vasculature, and promotes cellular activity consistent with tissue remodeling. Our prevascularization strategy may be useful to design large three-dimensional engineered tissues.
PMID: 18976155
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Chen X,Aledia AS,Popson SA,Him LK,Hughes CC,George S
University of California, Irvine, Biomedical Engineering, Irvine, California, United States; xchen1@uci.edu.
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Rapid anastomosis of endothelial precursor cell-derived vessels with host vasculature is promoted by a high density of co-transplanted fibroblasts.
Tissue Eng Part A. 2009 Sep 8;:
To ensure survival of engineered implantable tissues thicker than 2-3 mm, convection of nutrients and waste products to enhance the rate of transport will be required. Creating a network of vessels in vitro, prior to implantation (prevascularization), is one potential strategy to achieve this aim. In this study we developed 3-dimensional engineered vessel networks in vitro by co-culture of endothelial cells (EC) and fibroblasts in a fibrin gel for 7 days. Vessels formed by cord blood endothelial precursor cell-derived EC (EPC-EC) in the presence of a high density of fibroblasts created an interconnected tubular network within 4 days, compared to 5-7 days in the presence of a low density of fibroblasts. Vessels derived from human umbilical vein EC (HUVEC) in vitro showed similar kinetics. Implantation of the prevascularized tissues into immune compromised mice, however, revealed a dramatic difference in the ability of EPC-EC and HUVEC to form anastomoses with the host vasculature. Vascular beds derived from EPC-EC were perfused within one day of implantation whereas no HUVEC vessels were perfused at day 1. Furthermore, while almost 90% of EPC-EC derived vascular beds were perfused at day 3, only one third of HUVEC derived vascular beds were perfused. In both cases a high density of fibroblasts accelerated anastomosis by 2-3 days. We conclude that both EPC-EC and a high density of fibroblasts significantly accelerate the rate of functional anastomosis, and that prevascularizing an engineered tissue may be an effective strategy to enhance convective transport of nutrients in vivo.
PMID: 19737050
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Wilder-Smith P,Lee K,Guo S,Zhang J,Osann K,Chen Z,Messadi D
Beckman Laser Institute, University of California, Irvine, California 92612, USA. pwsmith@uci.edu
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In vivo diagnosis of oral dysplasia and malignancy using optical coherence tomography: preliminary studies in 50 patients.
Lasers Surg Med. 2009 Jul;41(5):353-7
BACKGROUND: In vivo, non-invasive optical coherence tomography (OCT) permits high-resolution imaging of tissue surfaces and subsurfaces, with the potential capability for detection and mapping of epithelial pathologies. PURPOSE: To evaluate the clinical capability of non-invasive in vivo OCT for diagnosing oral dysplasia and malignancy. EXPERIMENTAL DESIGN: In 50 patients with oral lesions, conventional clinical examination was followed by OCT imaging, then standard biopsy and histopathology. Two blinded, pre-standardized investigators separately diagnosed each lesion based on (1) OCT and (2) histopathology. RESULTS: Intra- and inter-observer agreement between diagnoses based on histopathology and imaging data was excellent, with lambda values between 0.844 and 0.896. Sensitivity and specificity were also very good. CONCLUSIONS: These data demonstrate the excellent capability of in vivo OCT for detecting and diagnosing oral premalignancy and malignancy in human subjects.
PMID: 19533765
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Wang A,Raniga PP,Lane S,Lu Y,Liu H
Department of Biological Chemistry, University of California, Irvine, CA 92697-1700, USA. h4liu@uci.edu
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Hyphal chain formation in Candida albicans: Cdc28-Hgc1 phosphorylation of Efg1 represses cell separation genes.
Mol Cell Biol. 2009 Aug;29(16):4406-16
Cell chain formation is a characteristic of filamentous growth in fungi. How it is regulated developmentally in multimorphic fungi is not known. In Candida albicans, degradation of septa during yeast growth is accomplished by enzymes encoded by Ace2 activated genes expressed in G(1). We found that phosphorylation of a conserved developmental regulator, Efg1, by the cyclin-dependent kinase Cdc28-Hgc1 (hypha-specific G(1) cyclin) downregulates Ace2 target genes during hyphal growth in G(1). A strain containing a threonine-to-alanine mutation at a conserved Cdc28 phosphorylation site of Efg1 displays a loss of hypha-specific repression of these genes and impaired cell chain formation, mimicking the hgc1 deletion, whereas a strain containing the threonine to aspartic acid mutation leads to a downregulation of these genes and cell chain formation during yeast growth. Furthermore, the phosphomimic mutation can suppress cell separation defects of hgc1. Efg1 also displays preferential association with Ace2 target gene promoters during hyphal growth. We show that convergent regulation of Ace2 and Efg1 defines the transcriptional program of cell chain formation.
PMID: 19528234
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Peralta ER,Edinger AL
Department of Developmental and Cell Biology, University of California-Irvine, Irvine, CA 92697-2300, USA.
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Ceramide-induced starvation triggers homeostatic autophagy.
Autophagy. 2009 Apr;5(3):407-9
Autophagy is triggered by ceramide, a sphingolipid that regulates diverse cellular processes including survival, differentiation and senescence. Both ceramide and autophagy play important, but incompletely understood, roles in type 2 diabetes and cancer. We reasoned that defining the connection between ceramide and autophagy might provide an important insight into these highly prevalent diseases. Our recently published work demonstrates that ceramide-induced autophagy is a homeostatic response to starvation caused by nutrient transporter downregulation. Preventing nutrient transporter loss or supplementation with transporter-independent nutrients protects cells from ceramide-induced death and delays the onset of autophagy. Thus, we propose a model where ceramide kills cells by inducing acute and severe intracellular nutrient limitation. Consistent with this idea, AMPK-deficient cells that are less able to deal with bioenergetic stress are also more sensitive to ceramide than wild-type cells. Our observation that gradually adapting cells to tolerate low levels of extracellular nutrients confers striking resistance to ceramide toxicity further supports this model. These results highlight the value of measuring nutrient transporter expression in cells undergoing protective autophagy. In addition, this novel mechanism for ceramide-induced cell death suggests new approaches to studying and treating multiple human diseases.
PMID: 19202357
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McDougall EM,Kolla SB,Santos RT,Gan JM,Box GN,Louie MK,Gamboa AJ,Kaplan AG,Moskowitz RM,Andrade LA,Skarecky DW,Osann KE,Clayman RV
Department of Urology, University of California, Irvine, Orange, California, USA. elspethm@uci.edu
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Preliminary study of virtual reality and model simulation for learning laparoscopic suturing skills.
J Urol. 2009 Sep;182(3):1018-25
PURPOSE: Repetitive practice of laparoscopic suturing and knot tying can facilitate surgeon proficiency in performing this reconstructive technique. We compared a silicone model and pelvic trainer to a virtual reality simulator in the learning of laparoscopic suturing and knot tying by laparoscopically naïve medical students, and evaluated the subsequent performance of porcine laparoscopic cystorrhaphy. MATERIALS AND METHODS: A total of 20 medical students underwent a 1-hour didactic session with video demonstration of laparoscopic suturing and knot tying by an expert laparoscopic surgeon. The students were randomized to a pelvic trainer (10) or virtual reality simulator (10) for a minimum of 2 hours of laparoscopic suturing and knot tying training. Within 1 week of the training session the medical students performed laparoscopic closure of a 2 cm cystotomy in a porcine model. Objective structured assessment of technical skills for laparoscopic cystorrhaphy was performed at the procedure by laparoscopic surgeons blinded to the medical student training format. A video of the procedure was evaluated with an objective structured assessment of technical skills by an expert laparoscopic surgeon blinded to medical student identity and training format. The medical students completed an evaluation questionnaire regarding the training format after the laparoscopic cystorrhaphy. RESULTS: All students were able to complete the laparoscopic cystorrhaphy. There was no difference between the pelvic trainer and virtual reality groups in mean +/- SD time to perform the porcine cystorrhaphy at 40 +/- 15 vs 41 +/- 10 minutes (p = 0.87) or the objective structured assessment of technical skills score of 8.8 +/- 2.3 vs 8.2 +/- 2.2 (p = 0.24), respectively. Bladder leak occurred in 3 (30%) of the pelvic trainer trained and 6 (60%) of the virtual reality trained medical student laparoscopic cystorrhaphy procedures (Fisher exact test p = 0.37). The only significant difference between the 2 groups was that 4 virtual reality trained medical students considered the training session too short compared to none of those trained on the pelvic trainer (p = 0.04). CONCLUSIONS: There is no significant difference between the pelvic trainer and virtual reality trained medical students in proficiency to perform laparoscopic cystorrhaphy in a pig model, although both groups require considerably more training before performing this procedure clinically. The pelvic trainer training may be more user-friendly for the novice surgeon to begin learning these challenging laparoscopic skills.
PMID: 19616797
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Nien CJ,Paugh JR,Massei S,Wahlert AJ,Kao WW,Jester JV
The Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA.
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Age-related changes in the meibomian gland.
Exp Eye Res. 2009 Sep 3;:
The purpose of this study was to characterize the age-related changes of the mouse meibomian gland. Eyelids from adult C57Bl/6 mice at 2, 6, 12 and 24 months of age were stained with specific antibodies against peroxisome proliferator activated receptor gamma (PPARgamma) to identify differentiating meibocytes, Oil Red O(ORO) to identify lipid, Ki67 nuclear antigen to identify cycling cells, B-lymphocyte-induced maturation protein-1 (Blimp1) to identify potential stem cells and CD45 to identify immune cells. Meibomian glands from younger mice (2 and 6 months) showed cytoplasmic and perinuclear staining with anti-PPARgamma antibodies with abundant ORO staining of small, intracellular lipid droplets. Meibomian glands from older mice (12 and 24 months) showed only nuclear PPARgamma localization with less ORO staining and significantly reduced acinar tissue (p<0.04). Acini of older mice also showed significantly reduced (p<0.004) numbers of Ki67 stained nuclei. While Blimp1 appeared to diffusely stain the superficial ductal epithelium, isolated cells were occasionally stained within the meibomian gland duct and acini of older mice that also stained with CD45 antibodies, suggesting the presence of infiltrating plasmacytoid cells.These findings suggest that there is altered PPARgamma receptor signaling in older mice that may underlie changes in cell cycle entry/proliferation, lipid synthesis and gland atrophy during aging. These results are consistent with the hypothesis that mouse meibomian glands undergo age-related changes similar to those identified in humans and may be used as a model for age-related meibomian gland dysfunction.
PMID: 19733559
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Jian Z,Yu Z,Yu L,Rao B,Chen Z,Tromberg BJ
Beckman Laser Institute, University of California, Irvine, California 92612, USA. zjian@uci.edu
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Speckle attenuation in optical coherence tomography by curvelet shrinkage.
Opt Lett. 2009 May 15;34(10):1516-8
We describe an algorithm based on shrinkage in the curvelet domain to attenuate speckles in optical coherence tomography (OCT) images. The algorithm exploits the curvelet transform's sparse representation of edge discontinuities that are common in OCT images and its ability to map signals and noise into different areas in the curvelet domain. The speckle attenuation is controlled by a single parameter that determines the threshold in the curvelet domain. Applying the algorithm to OCT images shows significant improvement of image quality.
PMID: 19448806
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Bateman AP,Nizkorodov SA,Laskin J,Laskin A
Department of Chemistry, University of California, Irvine, Irvine, California 92697, USA. nizkorod@uci.edu.
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Time-resolved molecular characterization of limonene/ozone aerosol using high-resolution electrospray ionization mass spectrometry.
Phys Chem Chem Phys. 2009 Sep 28;11(36):7931-42
Molecular composition of limonene/O(3) secondary organic aerosol (SOA) was investigated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) as a function of reaction time. SOA was generated by ozonation of d-limonene in a reaction chamber and sampled at different time intervals using a cascade impactor. The SOA samples were extracted into acetonitrile and analyzed using a HR-ESI-MS instrument with a resolving power of 100 000 (m/Deltam). The resulting mass spectra provided detailed information about the extent of oxidation inferred from the O : C ratios, double bond equivalency (DBE) factors, and aromaticity index (AI) values in hundreds of identified individual SOA species. The chemical composition of SOA was approximately the same for all size-fractionated samples studied in this experiment (0.05 to 0.5 mum range). The SOA constituents quickly reached an average O : C ratio of 0.43, which grew to 0.46 after one hour of additional oxidation of particles by the excess ozone. The dominant mechanism of oligomerization, inferred from high resolution ESI-MS data, was reaction between Criegee intermediates and stable first-generation products of limonene ozonolysis. Although the SOA composition was dominated by various oxidized aliphatic compounds, a small fraction of products appeared to contain aromatic rings. SOA generation was also studied in the presence of UV radiation and at elevated relative humidity (RH). The presence of UV radiation had a negligible effect on the SOA composition. The presence of water vapor resulted in a slight redistribution of peak intensities in the mass spectrum likely arising from hydration of certain SOA constituents. The data are consistent with fast production of the first-generation SOA constituents, including oligomers, followed by very slow aging processes that have a relatively small effect on the average molecular composition on the timescale of our experiments.
PMID: 19727500
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Finlayson-Pitts BJ
Department of Chemistry, University of California, Irvine, Irvine, CA 92697-2025, USA. bjfinlay@uci.edu
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Reactions at surfaces in the atmosphere: integration of experiments and theory as necessary (but not necessarily sufficient) for predicting the physical chemistry of aerosols.
Phys Chem Chem Phys. 2009 Sep 28;11(36):7760-79
While particles have significant deleterious impacts on human health, visibility and climate, quantitative understanding of their formation, composition and fates remains problematic. Indeed, in many cases, even qualitative understanding is lacking. One area of particular uncertainty is the nature of particle surfaces and how this determines interactions with gases in the atmosphere, including water, which is important for cloud formation and properties. The focus in this Perspective article is on some chemistry relevant to airborne particles and especially to reactions occurring on their surfaces. The intent is not to provide a comprehensive review, but rather to highlight a few selected examples of interface chemistry involving inorganic and organic species that may be important in the lower atmosphere. This includes sea salt chemistry, nitrate and nitrite ion photochemistry, organics on surfaces and heterogeneous reactions of oxides of nitrogen on proxies for airborne mineral dust and boundary layer surfaces. Emphasis is on the molecular level understanding that can only be gained by fully integrating experiment and theory to elucidate these complex systems.
PMID: 19727483
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Ngo-Metzger Q
University of California, Irvine, CA, USA. Qhngo@uci.edu
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Breaking bad news over the phone.
Am Fam Physician. 2009 Sep 1;80(5):520
PMID: 19725492
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Garcia JO,Grossman ED
Department of Cognitive Sciences, University of California Irvine, Irvine, CA 92697-5100, USA. jogarcia@uci.edu
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Motion opponency and transparency in the human middle temporal area.
Eur J Neurosci. 2009 Sep;30(6):1172-82
Motion transparency is the perception of multiple, moving surfaces within the same retinal location (for example, a ripple on the surface of a drifting stream), and is an interesting challenge to motion models because multiple velocities must be represented within the same region of space. When these motion vectors are in opposite directions, brief in duration and spatially constrained within a very local region, the result is little or no perceived motion (motion opponency). Both motion transparency and motion opponency inhibit the firing rate of single middle temporal area (MT) neurons as compared with the preferred direction alone, but neither generally influences the firing rate of primary visual cortex neurons. Surprisingly, neuroimaging studies of human middle temporal area (hMT+) have found less activation due only to motion opponency and an increase in neural responses for motion transparency. Here we parametrically manipulate the local balance between competing motion vectors and find an interaction between motion opponency and transparency in the population blood oxygen level-dependent (BOLD) response. We find reduced BOLD amplitude for motion opponency throughout visual cortex, but weakened responses due to perceptual transparency that is most apparent only within the hMT+. We interpret our results as evidence for two distinct mechanisms mediating opponency and transparency.
PMID: 19723288
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Anderson KD
Reeve-Irvine Research Center, Department of Neurological Surgery, University of California, 92697-1385, USA. kanderso@uci.edu
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Consideration of user priorities when developing neural prosthetics.
J Neural Eng. 2009 Oct;6(5):55003
For too long there has been separation of basic science, biomedical engineering, clinical science and the people these disciplines are serving. A key ingredient to understanding the real-life consequences of many neurologic disorders that produce physical disabilities, such as spinal cord injury, is to obtain valuable information from the individuals that are actually living with the disorders everyday. This information can be obtained in an objective and usable format, which can then be used to direct biomedical research in a manner that is meaningful to the intended beneficiaries. In particular, the field of neural prosthetics for spinal cord injury can make great strides if user input is obtained throughout the stages of development. Presented here is the perspective of a scientist who also has 20 years of experience living with a cervical spinal cord injury.
PMID: 19721182
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Shahrestani P,Leung HT,Le PK,Pak WL,Tse S,Ocorr K,Huang T
Ecology and Evolution, University of California Irvine, Irvine, California, United States of America.
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Heterozygous mutation of Drosophila Opa1 causes the development of multiple organ abnormalities in an age-dependent and organ-specific manner.
PLoS One. 2009;4(8):e6867
Optic Atrophy 1 (OPA1) is a ubiquitously expressed dynamin-like GTPase in the inner mitochondrial membrane. It plays important roles in mitochondrial fusion, apoptosis, reactive oxygen species (ROS) and ATP production. Mutations of OPA1 result in autosomal dominant optic atrophy (DOA). The molecular mechanisms by which link OPA1 mutations and DOA are not fully understood. Recently, we created a Drosophila model to study the pathogenesis of optic atrophy. Heterozygous mutation of Drosophila OPA1 (dOpa1) by P-element insertion results in no obvious morphological abnormalities, whereas homozygous mutation is embryonic lethal. In eye-specific somatic clones, homozygous mutation of dOpa1 causes rough (mispatterning) and glossy (decreased lens deposition) eye phenotypes in adult Drosophila. In humans, heterozygous mutations in OPA1 have been associated with mitochondrial dysfunction, which is predicted to affect multiple organs. In this study, we demonstrated that heterozygous dOpa1 mutation perturbs the visual function and an ERG profile of the Drosophila compound eye. We independently showed that antioxidants delayed the onset of mutant phenotypes in ERG and improved larval vision function in phototaxis assay. Furthermore, heterozygous dOpa1 mutation also caused decreased heart rate, increased heart arrhythmia, and poor tolerance to stress induced by electrical pacing. However, antioxidants had no effects on the dysfunctional heart of heterozygous dOpa1 mutants. Under stress, heterozygous dOpa1 mutations caused reduced escape response, suggesting abnormal function of the skeletal muscles. Our results suggest that heterozygous mutation of dOpa1 shows organ-specific pathogenesis and is associated with multiple organ abnormalities in an age-dependent and organ-specific manner.
PMID: 19718456
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Rosso D,Bolzonella D
Department of Civil and Environmental Engineering, University of California, Irvine CA 92697-2175, USA. bidui@uci.edu
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Carbon footprint of aerobic biological treatment of winery wastewater.
Water Sci Technol. 2009;60(5):1185-9
The carbon associated with wastewater and its treatment accounts for approximately 6% of the global carbon balance. Within the wastewater treatment industry, winery wastewater has a minor contribution, although it can have a major impact on wine-producing regions. Typically, winery wastewater is treated by biological processes, such as the activated sludge process. Biomass produced during treatment is usually disposed of directly, i.e. without digestion or other anaerobic processes. We applied our previously published model for carbon-footprint calculation to the areas worldwide producing yearly more than 10(6) m(3) of wine (i.e., France, Italy, Spain, California, Argentina, Australia, China, and South Africa). Datasets on wine production from the Food and Agriculture Organisation were processed and wastewater flow rates calculated with assumptions based on our previous experience. Results show that the wine production, hence the calculated wastewater flow, is reported as fairly constant in the period 2005-2007. Nevertheless, treatment process efficiency and energy-conservation may play a significant role on the overall carbon-footprint. We performed a sensitivity analysis on the efficiency of the aeration process (alphaSOTE per unit depth, or alphaSOTE/Z) in the biological treatment operations and showed significant margin for improvement. Our results show that the carbon-footprint reduction via aeration efficiency improvement is in the range of 8.1 to 12.3%.
PMID: 19717904
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Sarnecka BW,Lee MD
Department of Cognitive Sciences, University of California, Irvine, CA 92697, USA. sarnecka@uci.edu
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Levels of number knowledge during early childhood.
J Exp Child Psychol. 2009 Jul;103(3):325-37
Researchers have long disagreed about whether number concepts are essentially continuous (unchanging) or discontinuous over development. Among those who take the discontinuity position, there is disagreement about how development proceeds. The current study addressed these questions with new quantitative analyses of children's incorrect responses on the Give-N task. Using data from 280 children, ages 2 to 4 years, this study showed that most wrong answers were simply guesses, not counting or estimation errors. Their mean was unrelated to the target number, and they were lower-bounded by the numbers children actually knew. In addition, children learned the number-word meanings one at a time and in order; they treated the number words as mutually exclusive; and once they figured out the cardinal principle of counting, they generalized this principle to the rest of their count list. Findings support the 'discontinuity' account of number development in general and the 'knower-levels' account in particular.
PMID: 19345956
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Swanson JM,Entringer S,Buss C,Wadhwa PD
Department of Pediatrics, University of California, Irvine, School of Medicine, 19722 MacArthur Boulevard, Irvine, CA 92612-4480, USA. jmswanso@uci.edu
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Developmental origins of health and disease: environmental exposures.
Semin Reprod Med. 2009 Sep;27(5):391-402
The developmental origins of health and disease (DOHaD) approach has evolved over the past 20 years, and the current hypothesis proposes that fetal adaptations to intrauterine and maternal conditions during development shape structure and function of organs. Here we present a review of some environmental exposures that may trigger fetal maladaptations in these processes, including three examples: exposures to tobacco smoke, antidepressant medication, and folic acid deficits in the food supply. We provide a selected review of current research on the effects of each of these exposures on fetal development and birth outcomes, and use the DOHaD approach to suggest how these exposures may alter long-term outcomes. In the interpretation of this literature, we review the evidence of gene-environment interactions based on evaluation of biological pathways and evidence that some exposures to the fetus may be moderated by maternal and fetal genotypes. Finally, we use the design of the National Children's Study (now in progress) to propose how the DOHaD approach could be used to address questions that have emerged in this area that are relevant to reproductive medicine and subsequent health outcomes.
PMID: 19711249
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Wadhwa PD,Buss C,Entringer S,Swanson JM
Department of Pediatrics, University of California, Irvine, School of Medicine, 3117 GillespieNeuroscience Research Facility, Irvine, CA 92697-4260, USA. pwadhwa@uci.edu
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Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms.
Semin Reprod Med. 2009 Sep;27(5):358-68
"Barker's hypothesis" emerged almost 25 years ago from epidemiological studies of birth and death records that revealed a high geographic correlation between rates of infant mortality and certain classes of later adult deaths as well as an association between birthweight and rates of adult death from ischemic heart disease. These observations led to a theory that undernutrition during gestation was an important early origin of adult cardiac and metabolic disorders due to fetal programming that permanently shaped the body's structure, function, and metabolism and contributed to adult disease. This theory stimulated interest in the fetal origins of adult disorders, which expanded and coalesced approximately 5 years ago with the formation of an international society for developmental origins of health and disease (DOHaD). Here we review a few examples of the many emergent themes of the DOHaD approach, including theoretical advances related to predictive adaptive responses of the fetus to a broad range of environmental cues, empirical observations of effects of overnutrition and stress during pregnancy on outcomes in childhood and adulthood, and potential epigenetic mechanisms that may underlie these observations and theory. Next, we discuss the relevance of the DOHaD approach to reproductive medicine. Finally, we consider the next steps that might be taken to apply, evaluate, and extend the DOHaD approach.
PMID: 19711246
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Christley S,Nie Q,Xie X
Department of Mathematics, University of California Irvine, Irvine, CA, USA. scott.christley@uci.edu
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Incorporating existing network information into gene network inference.
PLoS One. 2009;4(8):e6799
One methodology that has met success to infer gene networks from gene expression data is based upon ordinary differential equations (ODE). However new types of data continue to be produced, so it is worthwhile to investigate how to integrate these new data types into the inference procedure. One such data is physical interactions between transcription factors and the genes they regulate as measured by ChIP-chip or ChIP-seq experiments. These interactions can be incorporated into the gene network inference procedure as a priori network information. In this article, we extend the ODE methodology into a general optimization framework that incorporates existing network information in combination with regularization parameters that encourage network sparsity. We provide theoretical results proving convergence of the estimator for our method and show the corresponding probabilistic interpretation also converges. We demonstrate our method on simulated network data and show that existing network information improves performance, overcomes the lack of observations, and performs well even when some of the existing network information is incorrect. We further apply our method to the core regulatory network of embryonic stem cells utilizing predicted interactions from two studies as existing network information. We show that including the prior network information constructs a more closely representative regulatory network versus when no information is provided.
PMID: 19710931
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Wohlford-Lenane CL,Meyerholz DK,Perlman S,Zhou H,Tran D,Selsted ME,McCray PB
Departments of Pediatrics, Pathology, Internal Medicine, Microbiology, and Carver College of Medicine, University of Iowa, Iowa City, IA 52242; Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA 92697.
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Rhesus Theta-Defensin Prevents Death in a Mouse Model of SARS Coronavirus Pulmonary Disease.
J Virol. 2009 Aug 26;:
We evaluated the efficacy of rhesus theta-defensin 1 (RTD-1), a novel cyclic antimicrobial peptide, as a prophylactic antiviral in a mouse model of SARS coronavirus (CoV) lung disease. BALB/c mice exposed to a mouse-adapted strain of SARS-CoV demonstrated 100% survival and modest reductions in lung pathology without reductions in virus titer when treated with two intranasal doses of RTD-1, while mortality in untreated mice was approximately 75%. RTD-1 treated, SARS-CoV infected mice displayed altered lung tissue cytokine responses 2 and 4 days post-infection compared to untreated animals, suggesting one possible mechanism of action for RTD-1 is immunomodulatory.
PMID: 19710146
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Zender R,Olshansky E
Program in Nursing Science, College of Health Sciences, University of California, Irvine, CA 92697, USA. rzender@uci.edu
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Women's mental health: depression and anxiety.
Nurs Clin North Am. 2009 Sep;44(3):355-64
Sex ratios for selected mental disorders such as major depressive disorder and anxiety disorder are much higher in women than men. Anxiety disorders constitute the most prevalent mental disorder in adults, and affect twice as many women as men. Depression and anxiety exist comorbidly and along with other mental disorders. This article focuses on depression and anxiety in women, and other conditions comorbid with depression or anxiety: cardiac disease, obesity, vitamin D deficiency, and irritable bowel syndrome.
PMID: 19683096
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Knudtson M,Tiso S,Phillips S
Program in Nursing Science, Department of Nursing, University of California, Irvine, Irvine, CA 92697, USA. mdknudts@uci.edu
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Human papillomavirus and the HPV vaccine: are the benefits worth the risks?
Nurs Clin North Am. 2009 Sep;44(3):293-9
Human papillomavirus (HPV) is the most commonly sexually transmitted infection in the United States. This article gives an overview and discussion of HPV virus types and transmission, and the quadrivalent vaccine now available to protect against it. Included are the nursing implications for the HPV vaccine related to education and counseling of parents, patients, and young adult women regarding HPV vaccination, for whom the vaccine is indicated.
PMID: 19683091
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Zender R,Olshansky E
Program in Nursing Science, College of Health Sciences, University of California, Irvine, CA 92697, USA. rzender@uci.edu
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Promoting wellness in women across the life span.
Nurs Clin North Am. 2009 Sep;44(3):281-91
For the purposes of this article, wellness is defined as an individual's subjective experience of overall life satisfaction in relation to physical, mental, emotional, spiritual, social, economic, occupational, and environmental dimensions. Women's wellness focuses on those aspects of well-being that pertain disproportionately, or solely, to women. Wellness includes but is not limited to physical, emotional and social aspects and disruptions that alter a woman's quality of life, such as reproductive and hormonal issues, bone health, gastrointestinal stress, and urinary incontinence. This article discusses women's wellness through the life span, from preconception through death, and considers the implications of these issues for the nursing profession.
PMID: 19683090
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Olshansky E
Program in Nursing Science, College of Health Sciences, University of California, Irvine, CA 92697, USA. e.olshansky@uci.edu
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Women's health. Preface.
Nurs Clin North Am. 2009 Sep;44(3):ix-x
PMID: 19683088
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Marchal-Crespo L,Reinkensmeyer DJ
Department of Mechanical and Aerospace Engineering, University of California, Irvine, CA, USA. lmarchal@uci.edu
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Review of control strategies for robotic movement training after neurologic injury.
J Neuroeng Rehabil. 2009;6:20
There is increasing interest in using robotic devices to assist in movement training following neurologic injuries such as stroke and spinal cord injury. This paper reviews control strategies for robotic therapy devices. Several categories of strategies have been proposed, including, assistive, challenge-based, haptic simulation, and coaching. The greatest amount of work has been done on developing assistive strategies, and thus the majority of this review summarizes techniques for implementing assistive strategies, including impedance-, counterbalance-, and EMG- based controllers, as well as adaptive controllers that modify control parameters based on ongoing participant performance. Clinical evidence regarding the relative effectiveness of different types of robotic therapy controllers is limited, but there is initial evidence that some control strategies are more effective than others. It is also now apparent there may be mechanisms by which some robotic control approaches might actually decrease the recovery possible with comparable, non-robotic forms of training. In future research, there is a need for head-to-head comparison of control algorithms in randomized, controlled clinical trials, and for improved models of human motor recovery to provide a more rational framework for designing robotic therapy control strategies.
PMID: 19531254
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