Medicine and Health Sciences Commons^™

Immunotherapy Of Cancer: Reprogramming Tumor-Immune Crosstalk, Kyle K. Payne, Amir A. Toor, Xiang-Yang Wang, Masoud H. Manjili

Microbiology and Immunology Publications

The advancement of cancer immunotherapy faces barriers which limit its efficacy. These include weak immunogenicity of the tumor, as well as immunosuppressive mechanisms which prevent effective antitumor immune responses. Recent studies suggest that aberrant expression of cancer testis antigens (CTAs) can generate robust antitumor immune responses, which implicates CTAs as potential targets for immunotherapy. However, the heterogeneity of tumor cells in the presence and quantity of CTA expression results in tumor escape from CTA-specific immune responses. Thus, the ability to modulate the tumor cell epigenome to homogenously induce expression of such antigens will likely render the tumor more immunogenic. Additionally, …

Endoplasmic Reticulum Stress And Lipid Metabolism, Huiping Zhou, Kezhong Zhang, Sabina Janciauskiene, Xiaokun Li

Microbiology and Immunology Publications

Endoplasmic reticulum (ER) is an elaborate cellular organelle essential for protein folding, calcium homeostasis, and lipid biosynthesis. Disruption of ER homeostasis imposes stress on the ER and subsequently leads to accumulation of unfolded or misfolded proteins in the ER lumen—a condition termed ER stress. In response to ER stress, a group of intracellular signaling pathways originated from the ER, collectively termed ER stress response, are activated to alter transcriptional and translational programs in the stressed cells. ER stress response has been linked to various human diseases associated with dyslipidemia, such as inflammatory diseases, obesity, diabetes, alcoholic and nonalcoholic liver diseases, …

Identification And Characterization Of A Novel Calcium-Activated Apyrase Fromcryptosporidium Parasites And Its Potential Role In Pathogenesis, Patricio A. Manque, Ute Woehlbier, Ana M. Lara, Fernando Tenjo, João M. Alves, Gregory A. Buck

Microbiology and Immunology Publications

Herein, we report the biochemical and functional characterization of a novel Ca2+-activated nucleoside diphosphatase (apyrase), CApy, of the intracellular gut pathogen Cryptosporidium. The purified recombinant CApy protein displayed activity, substrate specificity and calcium dependency strikingly similar to the previously described human apyrase, SCAN-1 (soluble calcium-activated nucleotidase 1). CApy was found to be expressed in both Cryptosporidium parvum oocysts and sporozoites, and displayed a polar localization in the latter, suggesting a possible co-localization with the apical complex of the parasite. In vitro binding experiments revealed that CApy interacts with the host cell in a dose-dependent fashion, implying the presence of …

Cpg And Interleukin-15 Synergize To Enhance Ifn- Production By Activated Cd8+ T Cells, Dustin Cobb, Siqi Guo, Ronald B. Smeltz

Microbiology and Immunology Publications

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN- by CD8+ T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN- production. The effect of CpG and IL-15 was also evident with CD8+ T …

Tumor Escape And Progression Under Immune Pressure, Masoud H. Manjili, Nejat Egilmez, Keith L. Knutson, Senthamil R. Selvan, Julie R. Ostberg

Microbiology and Immunology Publications

Although cancers develop and progress in immunocompetent hosts, immunological therapies for cancer have been proposed as alternative or complementary approaches to more standard therapy. It was initially thought that tumors were silent to the immune system, and that breaking immunological tolerance could result in immune-mediated tumor rejection. However, we have learned that cancer patients have preexisting immune responses against their tumor antigens which, nevertheless, fail to protect them, in part because of increased activity of the immune suppressor cells such as myeloid-derived suppressor cells (MDSC). Attempts to develop combinatorial therapies by depleting suppressor cells or blocking suppressor pathways and at …

Repertoire, Genealogy And Genomic Organization Of Cruzipain And Homologous Genes In Trypanosoma Cruzi, T. Cruzi-Like And Other Trypanosome Species, Luciana Lima, Paola A. Ortiz, Flavia M. Da Silva, Joao M. P. Alves, Myrna G. Serrano, Alane O. Cortez, Silvia C. Alfieri, Gregory A. Buck, Marta M. G. Teixeira

Microbiology and Immunology Publications

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei andTrypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, …

Genomic Sequence Analysis And Characterization Of Sneathia Amnii Sp. Nov, Michael D. Harwich, Myrna G. Serrano, Jennifer M. Fettweis, João M.P. Alves, Mark A. Reimers, Gregory A. Buck, Kimberly K. Jefferson

Microbiology and Immunology Publications

Background

Bacteria of the genus Sneathia are emerging as potential pathogens of the female reproductive tract. Species of Sneathia, which were formerly grouped with Leptotrichia, can be part of the normal microbiota of the genitourinary tracts of men and women, but they are also associated with a variety of clinical conditions including bacterial vaginosis, preeclampsia, preterm labor, spontaneous abortion, post-partum bacteremia and other invasive infections. Sneathia species also exhibit a significant correlation with sexually transmitted diseases and cervical cancer. BecauseSneathia species are fastidious and rarely cultured successfully in vitro; and the genomes of members of the …

Adam10 Regulates Transcription Factor Expression Required For Plasma Cell Function, Natalia S. Chaimowitz, Dae-Joong Kang, Lee M. Dean, Daniel H. Conrad

Microbiology and Immunology Publications

A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC) formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10Δ/ΔIgG1-cre+/−mice). Despite normal GC formation, antibody responses were impaired in ADAM10Δ/ΔIgG1-cre+/− mice, implicating ADAM10 in post-GC and extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC) numbers were normal in ADAM10Δ/ΔIgG1-cre+/− mice when compared to controls. However, PCs …

Mouse Rc/Btb2, A Member Of The Rcc1 Superfamily, Localizes To Spermatid Acrosomal Vesicles, Jiannan Wang, Maria E. Teves, Xuening Shen, David R. Nagarkatti-Gude, Rex A. Hess, Scott C. Henderson, Jerome F. Strauss Iii, Zhibing Zhang

Obstetrics and Gynecology Publications

Mouse RC/BTB2 is an unstudied protein of the RCC1 (Regulator of Chromosome Condensation) superfamily. Because of the significant remodeling of chromatin that occurs during spermiogenesis, we characterized the expression and localization of mouse RC/BTB2 in the testis and male germ cells. The Rc/btb2 gene yields two major transcripts: 2.3 kb Rc/btb2-s, present in most somatic tissues examined; and 2.5 kb Rc/btb2-t, which contains a unique non-translated exon in its 5′-UTR that is only detected in the testis. During the first wave of spermatogenesis, Rc/btb2-t mRNA is expressed from day 8 after birth, reaching highest levels of expression at day …

A Gga Plus U Approach To Effective Electronic Correlations In Thiolate-Ligated Iron-Oxo (Iv) Porphyrin, Justin Elenewski, John C. Hackett

Medicinal Chemistry Publications

High-valent oxo-metal complexes exhibit correlated electronic behavior on dense, low-lying electronic state manifolds, presenting challenging systems for electronic structure methods. Among these species, the iron-oxo (IV) porphyrin denoted Compound I occupies a privileged position, serving a broad spectrum of catalytic roles. The most reactive members of this family bear a thiolate axial ligand, exhibiting high activity toward molecular oxygen activation and substrate oxidation. The default approach to such systems has entailed the use of hybrid density functionals or multi-configurational/multireference methods to treat electronic correlation. An alternative approach is presented based on the GGA+U approximation to density functional theory, in …

Identification And Structural Characterization Of A New Three-Finger Toxin Hemachatoxin From Hemachatus Haemachatus Venom, Vallerinteavide Mavelli Girish, Sundramurthy Kumar, Lissa Joseph, Chacko Jobichen, R. Manjunatha Kini, J. Sivaraman

Biochemistry and Molecular Biology Publications

Snake venoms are rich sources of biologically active proteins and polypeptides. Three-finger toxins are non-enzymatic proteins present in elapid (cobras, kraits, mambas and sea snakes) and colubrid venoms. These proteins contain four conserved disulfide bonds in the core to maintain the three-finger folds. Although all three-finger toxins have similar fold, their biological activities are different. A new three-finger toxin (hemachatoxin) was isolated from Hemachatus haemachatus (Ringhals cobra) venom. Its amino acid sequence was elucidated, and crystal structure was determined at 2.43 Å resolution. The overall fold is similar to other three-finger toxins. The structure and sequence analysis revealed that the …

Metabolic Rate Regulates L1 Longevity In C. Elegans, Inhwan Lee, Amber Hendrix, Jeongho Kim, Jennifer Yoshimoto, Young-Jai You

Biochemistry and Molecular Biology Publications

Animals have to cope with starvation. The molecular mechanisms by which animals survive long-term starvation, however, are not clearly understood. When they hatch without food, C. elegans arrests development at the first larval stage (L1) and survives more than two weeks. Here we show that the survival span of arrested L1s, which we call L1 longevity, is a starvation response regulated by metabolic rate during starvation. A high rate of metabolism shortens the L1 survival span, whereas a low rate of metabolism lengthens it. The longer worms are starved, the slower they grow once they are fed, suggesting that L1 …

Early Hearing-Impairment Results In Crossmodal Reorganization Of Ferret Core Auditory Cortex, M. Alex Meredith, Brian L. Allman

Anatomy and Neurobiology Publications

Numerous investigations of cortical crossmodal plasticity, most often in congenital or early-deaf subjects, have indicated that secondary auditory cortical areas reorganize to exhibit visual responsiveness while the core auditory regions are largely spared. However, a recent study of adult-deafened ferrets demonstrated that core auditory cortex was reorganized by the somatosensory modality. Because adult animals have matured beyond their critical period of sensory development and plasticity, it was not known if adult-deafening and early-deafening would generate the same crossmodal results. The present study used young, ototoxically-lesioned ferrets () that, after maturation (avg. = 173 days old), showed significant hearing deficits (avg. …

Optogenetic Stimulation Of The Corticothalamic Pathway Affects Relay Cells And Gabaergic Neurons Differently In The Mouse Visual Thalamus, Chris W. D. Jurgens, Karen A. Bell, A. Rory Mcquiston, William Guido

Anatomy and Neurobiology Publications

The dorsal lateral geniculate nucleus (dLGN) serves as the primary conduit of retinal information to visual cortex. In addition to retinal input, dLGN receives a large feedback projection from layer VI of visual cortex. Such input modulates thalamic signal transmission in different ways that range from gain control to synchronizing network activity in a stimulus-specific manner. However, the mechanisms underlying such modulation have been difficult to study, in part because of the complex circuitry and diverse cell types this pathway innervates. To address this and overcome some of the technical limitations inherent in studying the corticothalamic (CT) pathway, we adopted …

Virginia Dental Journal (Vol. 89, No. 3, 2012)

Virginia Dental Journal

No abstract provided.

Crystal Structures Of Human Pyridoxal Kinase In Complex With The Neurotoxins, Ginkgotoxin And Theophylline: Insights Into Pyridoxal Kinase Inhibition, Amit Gandhi, Jigar V. Desai, Mohini S. Ghatge, Martino L. Di Salvo, Stefano Di Biase, Richmond Danso-Danquah, Faik N. Musayev, Roberto Contestabile, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. …

Species-Level Classification Of The Vaginal Microbiome, Jennifer M. Fettweis, Myrna G. Serrano, Nihar U. Sheth, Abigail L. Glascock, J. Paul Brooks, Kimberly K. Jefferson, Vaginal Microbiome Consortium, Gregory A. Buck

Microbiology and Immunology Publications

Background

The application of next-generation sequencing to the study of the vaginal microbiome is revealing the spectrum of microbial communities that inhabit the human vagina. High-resolution identification of bacterial taxa, minimally to the species level, is necessary to fully understand the association of the vaginal microbiome with bacterial vaginosis, sexually transmitted infections, pregnancy complications, menopause, and other physiological and infectious conditions. However, most current taxonomic assignment strategies based on metagenomic 16S rDNA sequence analysis provide at best a genus-level resolution. While surveys of 16S rRNA gene sequences are common in microbiome studies, few well-curated, body-site-specific reference databases of 16S rRNA …

Peripheral-Blood Stem Cells Versus Bone Marrow From Unrelated Donors, Claudio Anasetti, Brent R. Logan, Stephanie J. Lee, Edmund K. Waller, Daniel J. Weisdorf, John R. Wingard, Corey S. Cutler, Peter Westervelt, Ann Woolfrey, Stephen Couban, Gerhard Ehninger, Laura Johnston, Richard T. Maziarz, Michael A. Pulsipher, David L. Porter, Shin Mineishi, John M. Mccarty, Shakila P. Khan, Paolo Anderlini, William I. Bensinger, Susan F. Leitman, Scott D. Rowley, Christopher Bredeson, Shelly L. Carter, Mary M. Horowitz, Dennis L. Confer

Massey Comprehensive Cancer Center Publications

BACKGROUND

Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.

METHODS

We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September …

Alcohol Availability And Neighborhood Poverty And Their Relationship To Binge Drinking And Related Problems Among Drinkers In Committed Relationships, Christy M. Mckinney, Karen G. Chartier, Raul Caetano, T. Robert Harris

Social Work Publications

The authors examined the relationship of alcohol outlet density (AOD) and neighborhood poverty with binge drinking and alcohol-related problems among drinkers in married and cohabitating relationships and assessed whether these associations differed across sex. A U.S. national population couples survey was linked to U.S. Census data on AOD and neighborhood poverty. The 1,784 current drinkers in the survey reported on their binge drinking, alcohol-related problems, and other covariates. AOD was defined as the number of alcohol outlets per 10,000 persons and was obtained at the zip code level. Neighborhood poverty was as having a low (<20%) or high (≥20%) proportion of residents living in poverty at the census tract level. We used logistic regression for survey data to estimate odds ratios and 95% confidence intervals and tested for differences of associations by sex. Associations of neighborhood poverty with binge drinking were stronger for male than for female drinkers. The association of neighborhood poverty with alcohol-related problems was also stronger for men than for women. We observed no relationships between AOD and binge drinking or alcohol-related problems in this couples survey. Efforts to reduce binge drinking or alcohol-related problems among partners in committed relationships may have the greatest impact if targeted to male drinkers living in high-poverty neighborhoods. Binge drinking and alcohol-related problems, as well as residence in an impoverished neighborhood are risk factors for intimate partner violence (IPV) and other relationship conflicts.

Discovery Of Prostamide F2Α And Its Role In Inflammatory Pain And Dorsal Horn Nociceptive Neuron Hyperexcitability, Luisa Gatta, Fabiana Piscitelli, Catia Giordano, Serana Boccella, Aron H. Lichtman, Sebatino Maione, Vincenzo Di Marzo

Pharmacology and Toxicology Publications

It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2 in the spinal cord of rats with kaolin/λ-carrageenan-induced knee inflammation, and that this mechanism contributes to the analgesic effects of COX-2 inhibitors in this experimental model. We report the development of a specific method for the identification of endocannabinoid COX-2 metabolites, its application to measure the levels of these compounds in tissues, and the finding of prostamide F2α (PMF2α) in mice with knee inflammation. Whereas the levels of spinal endocannabinoids were not significantly altered by kaolin/λ-carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA, PMF2α, were strongly elevated. The …

The Interleukin 3 Gene (Il3) Contributes To Human Brain Volume Variation By Regulating Proliferation And Survival Of Neural Progenitors, Xiao-Jian Luo, Ming Li, Liang Huang, Khwangsik Nho, Min Deng, Qiang Chen, Daniel R. Weinberger, Alejandro A. Vasquez, Mark Rijpkema, Venkata S. Mattay, Andrew J. Saykin, Li Shen, Guillen Fernandez, Barbara Franke, Jing-Chun Chen, Xiang-Ning Chen, Jin-Kai Wang, Xiao Xiao, Xue-Bin Qi, Kun Xiang, Ying-Mei Peng, Xiang-Yu Cao, Yi Li, Xiao-Dong Shi, Lin Gan, Bing Su

Psychiatry Publications

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which …

Preserved Ex Vivo Inflammatory Status In Decidual Cells From Women With Preterm Labor And Subclinical Intrauterine Infection, Violeta Castro-Leyva, Aurora Espejel-Nunez, Gerardo Barroso, Veronica Zaga-Clavellina, Arturo Flores-Pliego, Iyari Morales-Mendez, Silvia Giono-Cerezo, Scott W. Walsh, Guadalupe Estrada-Gutierrez

Obstetrics and Gynecology Publications

Objective

To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.

Methods

Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E2 (PGE2) was measured by enzyme immunoassay.

Results …

Hemorrhage Detection And Segmentation In Traumatic Pelvic Injuries, Pavani Davuluri, Jie Wu, Yang Tang, Charles H. Cockrell, Kevin R. Ward, Kayvan Najarian, Rosalyn H. Hargraves

Electrical and Computer Engineering Publications

Automated hemorrhage detection and segmentation in traumatic pelvic injuries is vital for fast and accurate treatment decision making. Hemorrhage is the main cause of deaths in patients within first 24 hours after the injury. It is very time consuming for physicians to analyze all Computed Tomography (CT) images manually. As time is crucial in emergence medicine, analyzing medical images manually delays the decision-making process. Automated hemorrhage detection and segmentation can significantly help physicians to analyze these images and make fast and accurate decisions. Hemorrhage segmentation is a crucial step in the accurate diagnosis and treatment decision-making process. This paper presents …

Alternatives To Mixture Model Analysis Of Correlated Binomial Data, N. Rao Chaganty, Roy Sabo, Yihao Deng

Biostatistics Publications

While univariate instances of binomial data are readily handled with generalized linear models, cases of multivariate or repeated measure binomial data are complicated by the possibility of correlated responses. Likelihood-based estimation can be applied by using mixture distribution models, though this approach can present computational challenges. The logistic transformation can be used to bypass these concerns and allow for alternative estimating procedures. One popular alternative is the generalized estimating equation (GEE) method, though systematic errors can lead to infeasible correlation estimates or nonconvergence problems. Our approach is the coupling of quasileast squares (QLSs) method with a rarely used matrix factorization, …

Reduced Expression Of Inflammatory Genes In Deceased Donor Kidneys Undergoing Pulsatile Pump Preservation, Valeria Mas, Kellie J. Archer, Catherine I. Dumur, Mariano J. Scian, Jihee L. Suh, Anne L. King, Megan E. Wardius, Julie A. Straub, Marc P. Posner, Kenneth Brayman, Daniel Maluf

Biostatistics Publications

Background

The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys.

Methodology/Principal Findings

99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24–62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/−509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/−485 minutes) (P

Conclusions/Significance …

A Confirmatory Factor Analysis Of The Metabolic Syndrome In Adolescents: An Examination Of Sex And Racial/Ethnic Differences, Matthew J. Gurka, Christa L. Ice, Shumei S. Sun, Mark D. Deboer

Biostatistics Publications

Objective The metabolic syndrome (MetS) is a cluster of clinical indices that signals increased risk for cardiovascular disease and Type 2 diabetes. The diagnosis of MetS is typically based on cut-off points for various components, e.g. waist circumference and blood pressure. Because current MetS criteria result in racial/ethnic discrepancies, our goal was to use confirmatory factor analysis to delineate differential contributions to MetS by sub-group.

Research Design and Methods Using 1999–2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, …

Molecular Profiles Of Hcv Cirrhotic Tissues Derived In A Panel Of Markers With Clinical Utility For Hepatocellular Carcinoma Surveillance, Ricardo Gehrau, Kellie Archer, Valeria Mas, Daniel Maluf

Biostatistics Publications

Background

Early hepatocellular carcinoma (HCC) detection is difficult because low accuracy of surveillance tests. Genome-wide analyses were performed using HCV-cirrhosis with HCC to identify predictive signatures.

Methodology/Principal Findings

Cirrhotic liver tissue was collected from 107 HCV-infected patients with diagnosis of HCC at pre-transplantation and confirmed in explanted livers. Study groups included: 1) microarray hybridization set (n = 80) including patients without (woHCC = 45) and with (wHCC = 24) HCC, and with incidental HCC (iHCC = 11); 2) independent validation set (n = 27; woHCC = 16, wHCC = 11). Pairwise comparisons were performed using moderated t-test. FDR<1% was considered significant. L1-penalized logistic regression model was fit for woHCC and wHCC microarrays, and tested against iHCC. Prediction model genes were validated in independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progressing to mitosis; unregulated DNA damage check-points, and apoptosis. The prediction model included 17 molecules demonstrated 98.6% of accuracy and correctly classified 6 out of 11 undiagnosed iHCC cases. The best model performed even better in the additional independent set.

Conclusions/Significances

The …

Patient- And Population-Level Health Consequences Of Discontinuing Antiretroviral Therapy In Settings With Inadequate Hiv Treatment Availability, April D. Kimmel, Stephen C. Resch, Xavier Anglaret, Norman Daniels, Sue J. Goldie, Christine Daniel, Angela Y. Wong, Kenneth A. Freedberg, Milton C. Weinstein

Health Policy Publications

Background

In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes.

Methods

In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the …

One Fish, Two Fish, Red Fish, Blue Fish: Effects Of Price Frames, Brand Names, And Choice Set Size In Medicare Part D Insurance Plan Decisions, Andrew J. Barnes, Yaniv Hanoch, Stacey Wood, Pi-Ju Liu, Thomas Rice

Health Policy Publications

Because many seniors choose Medicare Part D plans offering poorer coverage at greater cost, the authors examined the effect of price frames, brand names, and choice set size on participants' ability to choose the lowest cost plan. A 2×2×2 within-subjects design was used with 126 participants aged 18 to 91 years old. Mouselab, a web-based program, allowed participants to choose drug plans across eight trials that varied using numeric or symbolic prices, real or fictitious drug plan names, and three or nine drug plan options. Results from the multilevel models suggest numeric versus symbolic prices decreased the likelihood of choosing …

Virginia Dental Journal (Vol. 89, No. 2, 2012)

Virginia Dental Journal

No abstract provided.