Digital Commons Network^™

Proton Magnetic Resonance Spectroscopy In Multiple Sclerosis, Balasrinivasa R Sajja, Jerry S Wolinsky, Ponnada A Narayana

Faculty, Staff and Student Publications

Proton magnetic resonance spectroscopy ((1)H-MRS) provides tissue metabolic information in vivo. This article reviews the role of MRS-determined metabolic alterations in lesions, normal-appearing white matter, gray matter, and spinal cord in advancing our knowledge of pathologic changes in multiple sclerosis (MS). In addition, the role of MRS in objectively evaluating therapeutic efficacy is reviewed. This potential metabolic information makes MRS a unique tool to follow MS disease evolution, understand its pathogenesis, evaluate the disease severity, establish a prognosis, and objectively evaluate the efficacy of therapeutic interventions.

Gstm1 And Gstt1 Null Polymorphisms And Risk Of Salivary Gland Carcinoma, Sayaka Kondo, Erich M. Sturgis, Fanglin Li, Qingyi Wei, Guojun Li

Faculty, Staff and Student Publications

Glutathione S-transferase (GST) genes detoxify and metabolize carcinogens, including oxygen free radicals which may contribute to salivary gland carcinogenesis. This cancer center-based case-control association study included 166 patients with incident salivary gland carcinoma (SGC) and 511 cancer-free controls. We performed multiplex polymerase chain reaction-based polymorphism genotyping assays for GSTM1 and GSTT1 null genotypes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with multivariable logistic regression analyses adjusted for age, sex, ethnicity, tobacco use, family history of cancer, alcohol use and radiation exposure. In our results, 27.7% of the SGC cases and 20.6% of the controls were null for …

Mutual Information For Testing Gene-Environment Interaction, Xuesen Wu, Li Jiin, Momiao Xiong

Faculty, Staff and Student Publications

Despite current enthusiasm for investigation of gene-gene interactions and gene-environment interactions, the essential issue of how to define and detect gene-environment interactions remains unresolved. In this report, we define gene-environment interactions as a stochastic dependence in the context of the effects of the genetic and environmental risk factors on the cause of phenotypic variation among individuals. We use mutual information that is widely used in communication and complex system analysis to measure gene-environment interactions. We investigate how gene-environment interactions generate the large difference in the information measure of gene-environment interactions between the general population and a diseased population, which motives …

Enhanced Estrogen-Induced Proliferation In Obese Rat Endometrium, Qian Zhang, Qi Shen, Joseph Celestino, Michael R Milam, Shannon N Westin, Robin A Lacour, Larissa A Meyer, Gregory L Shipley, Peter J A Davies, Lei Deng, Adrienne S Mccampbell, Russell R Broaddus, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals.

STUDY DESIGN: Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol.

RESULTS: No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed …

Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti

Faculty, Staff and Student Publications

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Improving Follow-Up Of Abnormal Cancer Screens Using Electronic Health Records: Trust But Verify Test Result Communication, Hardeep Singh, Lindsey Wilson, Laura A Petersen, Mona K Sawhney, Brian Reis, Donna Espadas, Dean F Sittig

Faculty, Staff and Student Publications

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response.

METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. …

Ontology Driven Integration Platform For Clinical And Translational Research, Parsa Mirhaji, Min Zhu, Mattew Vagnoni, Elmer V. Bernstam, Jiajie Zhang, Jack W. Smith

Faculty, Staff and Student Publications

Semantic Web technologies offer a promising framework for integration of disparate biomedical data. In this paper we present the semantic information integration platform under development at the Center for Clinical and Translational Sciences (CCTS) at the University of Texas Health Science Center at Houston (UTHSC-H) as part of our Clinical and Translational Science Award (CTSA) program. We utilize the Semantic Web technologies not only for integrating, repurposing and classification of multi-source clinical data, but also to construct a distributed environment for information sharing, and collaboration online. Service Oriented Architecture (SOA) is used to modularize and distribute reusable services in a …

Reduced Neutrophil Count In People Of African Descent Is Due To A Regulatory Variant In The Duffy Antigen Receptor For Chemokines Gene, David Reich, Michael A. Nalls, W H Linda Kao, Ermeg L. Akylbekova, Arti Tandon, Nick Patterson, James Mullikin, Wen-Chi Hsueh, Ching-Yu Cheng, Josef Coresh, Eric Boerwinkle, Man Li, Alicja Waliszewska, Julie Neubauer, Rongling Li, Tennille S. Leak, Lynette Ekunwe, Joe C. Files, Cheryl L. Hardy, Joseph M. Zmuda, Herman A. Taylor, Elad Ziv, Tamara B. Harris, James G. Wilson

Faculty, Staff and Student Publications

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. to identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. …

Comparative Efficacy Of 2 Topical Anesthetics For The Placement Of Orthodontic Temporary Anchorage Devices, Derek S Reznik, Arthur H Jeske, Jung-Wei Chen, Jeryl English

Faculty, Staff and Student Publications

This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P …

Incidental Detection Of An Occult Oral Malignancy With Autofluorescence Imaging: A Case Report, Nadarajah Vigneswaran, Sheila Koh, Ann Gillenwater

Faculty, Staff and Student Publications

BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma.

CASE DESCRIPTION: A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during …

Computerized Provider Order Entry Adoption: Implications For Clinical Workflow, Emily M. Campbell, Kenneth P. Guappone, Dean F. Sittig, Richard H. Dykstra, Joan S. Ash

Faculty, Staff and Student Publications

OBJECTIVE: To identify and describe unintended adverse consequences related to clinical workflow when implementing or using computerized provider order entry (CPOE) systems. METHODS: We analyzed qualitative data from field observations and formal interviews gathered over a three-year period at five hospitals in three organizations. Five multidisciplinary researchers worked together to identify themes related to the impacts of CPOE systems on clinical workflow. RESULTS: CPOE systems can affect clinical work by 1) introducing or exposing human/computer interaction problems, 2) altering the pace, sequencing, and dynamics of clinical activities, 3) providing only partial support for the work activities of all types of …

Taxonomy Development And Knowledge Representation Of Nurses' Personal Cognitive Artifacts, Sharon Mclane, James P Turley

Faculty, Staff and Student Publications

Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive …

Upregulation Of Defensins In Burn Sheep Small Intestine, Brian J Poindexter, Gordon L Klein, Stephen M Milner, Roger J Bick

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to visualize and localize the sheep antimicrobials, beta-defensins 1, 2, and 3, (SBD-1, SBD-2, SBD-3), sheep neutrophil defensin alpha (SNP-1), and the cathelicidin LL-37 in sheep small intestine after burn injury, our hypothesis being that these compounds would be upregulated in an effort to overcome a compromised endothelial lining. Response to burn injury includes the release of proinflammatory cytokines and systemic immune suppression that, if untreated, can progress to multiple organ failure and death, so protective mechanisms have to be initiated and implemented.

METHODS: Tissue sections were probed with antibodies to the antimicrobials …

Structure Altering Effects Of A Multicomponent Reading Intervention: An Application Of The Direct And Inferential Mediation (Dime) Model Of Reading Comprehension In Upper Elementary Grades, Georgios Kalantzis, Harel Z Shouval

Faculty, Staff and Student Publications

BACKGROUND: Synaptic plasticity underlies many aspect of learning memory and development. The properties of synaptic plasticity can change as a function of previous plasticity and previous activation of synapses, a phenomenon called metaplasticity. Synaptic plasticity not only changes the functional connectivity between neurons but in some cases produces a structural change in synaptic spines; a change thought to form a basis for this observed plasticity. Here we examine to what extent structural plasticity of spines can be a cause for metaplasticity. This study is motivated by the observation that structural changes in spines are likely to affect the calcium dynamics …

Molluscan Memory Of Injury: Evolutionary Insights Into Chronic Pain And Neurological Disorders, Edgar T Walters, Leonid L Moroz

Faculty, Staff and Student Publications

Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan …

Is Paromomycin An Effective And Safe Treatment Against Cutaneous Leishmaniasis? A Meta-Analysis Of 14 Randomized Controlled Trials, Dae Hyun Kim, Hye Jin Chung, Joachim Bleys, Reza F Ghohestani

Faculty, Staff and Student Publications

BACKGROUND: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting.

METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled …

Morphoproteomic Evidence Of Constitutively Activated And Overexpressed Mtor Pathway In Cervical Squamous Carcinoma And High Grade Squamous Intraepithelial Lesions, Wei Feng, Xiuzhen Duan, Jinsong Liu, Jianguo Xiao, Robert E Brown

Faculty, Staff and Student Publications

Human papilloma virus (HPV) infection of the uterine cervix is linked to the pathogenesis of cervical cancer. Preclinical in vitro and in vivo studies using HPV-containing human cervical carcinoma cell lines have shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, erlotinib, can induce growth delay of xenografts. Activation of Akt and mTOR are also observed in cervical squamous cell carcinoma and, the expression of phosphorylated mTOR was reported to serve as a marker to predict response to chemotherapy and survival of cervical cancer patients. Therefore, we investigated: a) the expression …

Denaturation And Unfolding Of Human Anaphylatoxin C3a: An Unusually Low Covalent Stability Of Its Native Disulfide Bonds, Jui-Yoa Chang, Curtis C-J Lin, Silvia Salamanca, Michael K Pangburn, Rick A Wetsel

Faculty, Staff and Student Publications

The complement C3a anaphylatoxin is a major molecular mediator of innate immunity. It is a potent activator of mast cells, basophils and eosinophils and causes smooth muscle contraction. Structurally, C3a is a relatively small protein (77 amino acids) comprising a N-terminal domain connected by 3 native disulfide bonds and a helical C-terminal segment. The structural stability of C3a has been investigated here using three different methods: Disulfide scrambling; Differential CD spectroscopy; and Reductive unfolding. Two uncommon features regarding the stability of C3a and the structure of denatured C3a have been observed in this study. (a) There is an unusual disconnection …

Increased Myocardial Susceptibility To Repetitive Ischemia With High-Fat–Diet-Induced Obesity, Geeta D Thakker, Nikolaos G Frangogiannis, Pawel T Zymek, Saumya Sharma, Joe L Raya, Philip M Barger, Heinrich Taegtmeyer, Mark L Entman, Christie M Ballantyne

Faculty, Staff and Student Publications

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol …

Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu

Faculty, Staff and Student Publications

Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and …

Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong

Faculty, Staff and Student Publications

It is system dynamics that determines the function of cells, tissues and organisms. to develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of …

Mrsa Usa300 Clone And Vref--A Us-Colombian Connection?, Cesar A Arias, Sandra Rincon, Shahreen Chowdhury, Ernesto Martínez, Wilfrido Coronell, Jinnethe Reyes, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

No abstract provided.

Sustained Attention In Children With Two Etiologies Of Early Hydrocephalus, Maegan D. Swartwout, Paul T. Cirino, Amy W. Hampson, Jack M. Fletcher, Michael E. Brandt, Maureen Dennis

Faculty, Staff and Student Publications

Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive …

3d Mprage Improves Classification Of Cortical Lesions In Multiple Sclerosis, F Nelson, A Poonawalla, P Hou, J S Wolinsky, P A Narayana

Faculty, Staff and Student Publications

BACKGROUND: Gray matter lesions are known to be common in multiple sclerosis (MS) and are suspected to play an important role in disease progression and clinical disability. A combination of magnetic resonance imaging (MRI) techniques, double-inversion recovery (DIR), and phase-sensitive inversion recovery (PSIR), has been used for detection and classification of cortical lesions. This study shows that high-resolution three-dimensional (3D) magnetization-prepared rapid acquisition with gradient echo (MPRAGE) improves the classification of cortical lesions by allowing more accurate anatomic localization of lesion morphology.

METHODS: 11 patients with MS with previously identified cortical lesions were scanned using DIR, PSIR, and 3D MPRAGE. …

Rationale For Reading Fluconazole Mics At 24 Hours Rather Than 48 Hours When Testing Candida Spp By The Clsi M27-A2 Standard Method, Luis Ostrosky-Zeichner, John H Rex, Michael A Pfaller, Daniel J Diekema, Barbara D Alexander, David Andes, Steven D Brown, Vishnu Chaturvedi, Mahmoud A Ghannoum, Cindy C Knapp, Daniel J Sheehan, Thomas J Walsh

Faculty, Staff and Student Publications

We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata.

Poly(A)-Binding Protein-Interacting Protein 1 Binds To Eukaryotic Translation Initiation Factor 3 To Stimulate Translation, Yvan Martineau, Mélanie C Derry, Xiaoshan Wang, Akiko Yanagiya, Juan José Berlanga, Ann-Bin Shyu, Hiroaki Imataka, Kalle Gehring, Nahum Sonenberg

Faculty, Staff and Student Publications

Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip) proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism. Here, we describe the interaction between Paip1 and eIF3, which is direct, RNA independent, and mediated via the eIF3g (p44) subunit. Stimulation of translation by Paip1 in vivo was decreased upon deletion of the N-terminal sequence containing the eIF3-binding domain and upon silencing of PABP or several eIF3 subunits. We also show the formation of ternary complexes composed of Paip1-PABP-eIF4G and …

Concept, Design And Implementation Of A Cardiovascular Gene-Centric 50 K Snp Array For Large-Scale Genomic Association Studies, Brendan J. Keating, Sam Tischfield, Sarah S. Murray, Tushar Bhangale, Thomas S. Price, Joseph T. Glessner, Luana Galver, Jeffrey C. Barrett, Struan F A Grant, Deborah N. Farlow, Hareesh R. Chandrupatla, Mark Hansen, Saad Ajmal, George J. Papanicolaou, Yiran Guo, Mingyao Li, Stephanie Derohannessian, Paul I W. De Bakker, Swneke D. Bailey, Alexandre Montpetit, Andrew C. Edmondson, Kent Taylor, Xiaowu Gai, Susanna S. Wang, Myriam Fornage, Tamim Shaikh, Leif Groop, Michael Boehnke, Alistair S. Hall, Andrew T. Hattersley, Edward Frackelton, Nick Patterson, Charleston K W Chiang, Cecelia E. Kim, Richard R. Fabsitz, Willem Ouwehand, Alkes L. Price, Patricia Munroe, Mark Caulfield, Thomas Drake, Eric Boerwinkle, David Reich, A Stephen Whitehead, Thomas P. Cappola, Nilesh J. Samani, A Jake Lusis, Eric Schadt, James G. Wilson, Wolfgang Koenig, Mark I. Mccarthy, Sekar Kathiresan, Stacey B. Gabriel, Hakon Hakonarson, Sonia S. Anand, Muredach Reilly, James C. Engert, Deborah A. Nickerson, Daniel J. Rader, Joel N. Hirschhorn, Garret A. Fitzgerald

Faculty, Staff and Student Publications

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 …

Aggressive Vs Conservative Phototherapy For Infants With Extremely Low Birth Weight, Brenda H Morris, William Oh, Jon E Tyson, David K Stevenson, Dale L Phelps, T Michael O'Shea, Georgia E Mcdavid, Rebecca L Perritt, Krisa P Van Meurs, Betty R Vohr, Cathy Grisby, Qing Yao, Claudia Pedroza, Abhik Das, W Kenneth Poole, Waldemar A Carlo, Shahnaz Duara, Abbot R Laptook, Walid A Salhab, Seetha Shankaran, Brenda B Poindexter, Avroy A Fanaroff, Michele C Walsh, Maynard R Rasmussen, Barbara J Stoll, C Michael Cotten, Edward F Donovan, Richard A Ehrenkranz, Ronnie Guillet, Rosemary D Higgins

Faculty, Staff and Student Publications

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).

METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.

RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 …

A Schiff Base Connectivity Switch In Sensory Rhodopsin Signaling, Oleg A Sineshchekov, Jun Sasaki, Brian J Phillips, John L Spudich

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Sensory rhodopsin I (SRI) in Halobacterium salinarum acts as a receptor for single-quantum attractant and two-quantum repellent phototaxis, transmitting light stimuli via its bound transducer HtrI. Signal-inverting mutations in the SRI-HtrI complex reverse the single-quantum response from attractant to repellent. Fast intramolecular charge movements reported here reveal that the unphotolyzed SRI-HtrI complex exists in two conformational states, which differ by their connection of the retinylidene Schiff base in the SRI photoactive site to inner or outer half-channels. In single-quantum photochemical reactions, the conformer with the Schiff base connected to the cytoplasmic (CP) half-channel generates an attractant signal, whereas the conformer …