Recent Stanford Publications in PubMed
- T-cell metabolism in autoimmune disease.Yang Z, Matteson EL, Goronzy JJ, Weyand CMArthritis Res Ther
- Survey on patient safety climate in public hospitals in China.Zhou P, Bundorf MK, Gu J, He X, Xue DBMC Health Serv Res
- Entamoeba histolytica rhomboid protease 1 has a role in migration and motility as validated by two independent genetic approaches.Rastew E, Morf L, Singh UExp Parasitol
- Nanotechnology and neurophysiology.Angle MR, Cui B, Melosh NACurr Opin Neurobiol
- Associations between self-reported pest treatments and pesticide concentrations in carpet dust.Deziel NC, Colt JS, Kent EE, Gunier RB, Reynolds P, Booth B, Metayer C, Ward MHEnviron Health
- The role of evidence and context for implementing a multimodal intervention to increase HIV testing.Bokhour BG, Saifu H, Goetz MB, Fix GM, Burgess J, Fletcher MD, Knapp H, Asch SMImplement Sci
- Updating emotional content in recovered depressed individuals: Evaluating deficits in emotion processing following a depressive episode.Levens SM, Gotlib IHJ Behav Ther Exp Psychiatry
- Implementing highly specialized and evidence-based pediatric eating disorder treatment: protocol for a mixed methods evaluation.Couturier J, Kimber M, Lock J, Barwick M, McVey G, Findlay S, Webb C, Boettcher M, Niccols A, Woodford TImplement Sci
- Naive T Cell Maintenance and Function in Human Aging.Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CMJ Immunol
- Nomenclature of Toso, Fas Apoptosis Inhibitory Molecule 3, and IgM FcR.Kubagawa H, Carroll MC, Jacob CO, Lang KS, Lee KH, Mak T, McAndrews M, Morse HC, Nolan GP, Ohno H, Richter GH, Seal R, Wang JY, Wiestner A, Coligan JEJ Immunol
- Comparison of Pain Score Reduction Using Triamcinolone vs. Betamethasone in Transforaminal Epidural Steroid Injections for Lumbosacral Radicular Pain.McCormick Z, Kennedy DJ, Garvan C, Rivers E, Temme K, Margolis S, Zander E, Rohr A, Smith MC, Plastaras CAm J Phys Med Rehabil
- A Secreted Effector Protein of Ustilago maydis Guides Maize Leaf Cells to Form Tumors.Redkar A, Hoser R, Schilling L, Zechmann B, Krzymowska M, Walbot V, Doehlemann GPlant Cell
- Crowd-sourced assessment of surgical skills in cricothyrotomy procedure.Aghdasi N, Bly R, White LW, Hannaford B, Moe K, Lendvay TSJ Surg Res
- Cropped, Drosophila transcription factor AP-4, controls tracheal terminal branching and cell growth.Wong MM, Liu MF, Chiu SKBMC Dev Biol
- An evidence-based approach to identify aging-related genes in Caenorhabditis elegans.Callahan A, Cifuentes JJ, Dumontier MBMC Bioinformatics
- Cellular mechanisms of alveolar pathology in childhood interstitial lung diseases: current insights from mouse genetics.Kuo CS, Desai TJCurr Opin Pediatr
- Complementary and alternative medicine in pulmonology.Mark JD, Chung YCurr Opin Pediatr
- Recent advances in cystic fibrosis.Milla CE, Moss RBCurr Opin Pediatr
- The pediatric microbiome and the lung.Tracy M, Cogen J, Hoffman LRCurr Opin Pediatr
- Characterization of the enhancement of zero valent iron on microbial azo reduction.Fang Y, Xu M, Wu WM, Chen X, Sun G, Guo J, Liu XBMC Microbiol
- MicroRNA-mediated Regulation of Differentiation and Trans-differentiation in Stem Cells.Ong SG, Lee WH, Kodo K, Wu JCAdv Drug Deliv Rev
- Infusion pump-mediated mechanical hemolysis in pediatric patients.Hughes J, McNaughton J, Andrews J, George T, Bergero C, Pyke-Grimm K, Galel SA, Gonzalez C, Goodnough LT, Fontaine MJAnn Clin Lab Sci
- PRAME Immunohistochemical Staining in Transient Abnormal Myelopoiesis and Myeloid Leukemia Associated with Down Syndrome.Chisholm KM, Rivetta CV, Heerema-McKenney AAnn Clin Lab Sci
- Non-invasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing.Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, Takahashi K, Glover C, Keane C, Kihira S, Visser B, Callahan J, Kong KA, Faham M, Corbelli KS, Miklos D, Advani RH, Levy R, Hicks RJ, Hertzberg M, Ohgami RS, Gandhi MK, Diehn M, Alizadeh AABlood
- Unraveling the 3D genome: genomics tools for multiscale exploration.Risca VI, Greenleaf WJTrends Genet
- Identifying multi-locus chromatin contacts in human cells using tethered multiple 3C.Ay F, Vu TH, Zeitz MJ, Varoquaux N, Carette JE, Vert JP, Hoffman AR, Noble WSBMC Genomics
- Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies.Wojcik GL, Kao WH, Duggal PBMC Genet
- The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial.Floege J, Kubo Y, Floege A, Chertow GM, Parfrey PSClin J Am Soc Nephrol
- Rates and Predictors of Newly Diagnosed HIV infection among Veterans Receiving Routine Once-Per-Lifetime HIV Testing in the Veterans Health Administration.Goetz MB, Hoang T, Kan VL, Rimland D, Rodriguez-Barradas MC, Asch SMJ Acquir Immune Defic Syndr
- A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.Guenther CA, Wang Z, Li E, Tran MC, Logan CY, Nusse R, Pantalena-Filho L, Yang GP, Kingsley DMBone
- Measuring semantic similarities by combining gene ontology annotations and gene co-function networks.Peng J, Uygun S, Kim T, Wang Y, Rhee SY, Chen JBMC Bioinformatics
- Higher Vagal Activity as Related to Survival in Patients With Advanced Breast Cancer: An Analysis of Autonomic Dysregulation.Giese-Davis J, Wilhelm FH, Tamagawa R, Palesh O, Neri E, Taylor CB, Kraemer HC, Spiegel DPsychosom Med
- Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment.Yang CF, Meyerhoff RR, Stephens SJ, Singhapricha T, Toomey CB, Anderson KL, Kelsey C, Harpole D, D'Amico TA, Berry MFAnn Thorac Surg
- Future of Anesthesiology Is Perioperative Medicine: A Call for Action.Kain ZN, Fitch JC, Kirsch JR, Mets B, Pearl RGAnesthesiology
- Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring.Case LK, Wall EH, Osmanski EE, Dragon JA, Saligrama N, Zachary JF, Lemos B, Blankenhorn EP, Teuscher CGenome Biol
T-cell metabolism in autoimmune disease.
Arthritis Res Ther. 2015;17(1):29
Authors: Yang Z, Matteson EL, Goronzy JJ, Weyand CM
Cancer cells have long been known to fuel their pathogenic growth habits by sustaining a high glycolytic flux, first described almost 90 years ago as the so-called Warburg effect. Immune cells utilize a similar strategy to generate the energy carriers and metabolic intermediates they need to produce biomass and inflammatory mediators. Resting lymphocytes generate energy through oxidative phosphorylation and breakdown of fatty acids, and upon activation rapidly switch to aerobic glycolysis and low tricarboxylic acid flux. T cells in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have a disease-specific metabolic signature that may explain, at least in part, why they are dysfunctional. RA T cells are characterized by low adenosine triphosphate and lactate levels and increased availability of the cellular reductant NADPH. This anti-Warburg effect results from insufficient activity of the glycolytic enzyme phosphofructokinase and differentiates the metabolic status in RA T cells from those in cancer cells. Excess production of reactive oxygen species and a defect in lipid metabolism characterizes metabolic conditions in SLE T cells. Owing to increased production of the glycosphingolipids lactosylceramide, globotriaosylceramide and monosialotetrahexosylganglioside, SLE T cells change membrane raft formation and fail to phosphorylate pERK, yet hyperproliferate. Borrowing from cancer metabolomics, the metabolic modifications occurring in autoimmune disease are probably heterogeneous and context dependent. Variations of glucose, amino acid and lipid metabolism in different disease states may provide opportunities to develop biomarkers and exploit metabolic pathways as therapeutic targets.
PMID: 25890351 [PubMed - as supplied by publisher]
Survey on patient safety climate in public hospitals in China.
BMC Health Serv Res. 2015;15(1):53
Authors: Zhou P, Bundorf MK, Gu J, He X, Xue D
BACKGROUND: Patient safety climate has been recognized as a core determinant for improving safety in hospitals. Describing workforce perceptions of patient safety climate is an important part of safety climate management. This study aimed to describe staff's perceptions of patient safety climate in public hospitals in Shanghai, China and to determine how perceptions of patient safety climate differ between different types of workers in the U.S. and China.
METHODS: Survey of employees of 6 secondary, general public hospitals in Shanghai conducted during 2013 using a modified version of the U.S. Patient Safety Climate in Health Care Organizations (PSCHO) tool. The percentage of "problematic responses" (PPRs) was used to measure safety climate, and the PPRs were compared among employees with different job types, using χ (2) tests and multivariate regression models.
RESULTS: Perceptions of patient safety climate were relatively positive among hospital employees and similar to those of employees in U.S. hospitals along most dimensions. For workers in Chinese hospitals, the scales of "fear of blame" and "fear of shame" had the highest PPRs, whereas in the United States the scale of "fear of shame" had among the lowest PPRs. As in the United States, hospital managers in China perceived a more positive patient safety climate overall than other types of personnel.
CONCLUSIONS: "Fear of shame" and "fear of blame" may be important barriers to improvement of patient safety in Chinese hospitals. Research on the effect of patient safety climate on outcomes is necessary to implement effective polices to improve patient safety and quality outcomes in China.
PMID: 25890169 [PubMed - as supplied by publisher]
Entamoeba histolytica rhomboid protease 1 has a role in migration and motility as validated by two independent genetic approaches.
Exp Parasitol. 2015 Apr 15;
Authors: Rastew E, Morf L, Singh U
Rhomboid proteins represent a recently discovered family of intramembrane proteases present in a broad range of organisms and with increasing links to human diseases. The enteric parasite Entamoeba histolytica has evolved multiple mechanisms to adapt to the human host environment and establish infection. Our recent studies identified EhROM1 as a functional E. histolytica rhomboid protease with roles in adhesion to and phagocytosis of host cells. Since those studies were performed in a non-virulent strain, roles in parasite virulence could not be assessed. We focused this study on the comparison and validation of two genetic manipulation techniques: overexpression of a dominant-negative catalytic mutant of EhROM1 and knock down of EhROM1 using a RNAi-based silencing approach followed by functional studies of phenotypic analyses in virulent parasites. Both the EhROM1 catalytic mutant and parasites with EhROM1 downregulation were reduced in cytotoxicity, hemolytic activity, and directional and non-directional transwell migration. Importantly, the role for EhROM1 in cell migration mimics similar roles for rhomboid proteases from mammalian and apicomplexan systems. However, the EhROM1 catalytic mutant and EhROM1 downregulation parasites had different phenotypes for erythrophagocytosis, while complement resistance was not affected in either strain. In summary, in this study we genetically manipulated E. histolytica rhomboid protease EhROM1 by two different approaches and identified similarly attenuated phenotypes by both approaches, suggesting a novel role for EhROM1 in amebic motility.
PMID: 25889553 [PubMed - as supplied by publisher]
Nanotechnology and neurophysiology.
Curr Opin Neurobiol. 2015 Apr 15;32:132-140
Authors: Angle MR, Cui B, Melosh NA
Neuroscience would be revolutionized by a technique to measure intracellular electrical potentials that would not disrupt cellular physiology and could be massively parallelized. Though such a technology does not yet exist, the technical hurdles for fabricating minimally disruptive, solid-state electrical probes have arguably been overcome in the field of nanotechnology. Nanoscale devices can be patterned with features on the same length scale as biological components, and several groups have demonstrated that nanoscale electrical probes can measure the transmembrane potential of electrogenic cells. Developing these nascent technologies into robust intracellular recording tools will now require a better understanding of device-cell interactions, especially the membrane-inorganic interface. Here we review the state-of-the art in nanobioelectronics, emphasizing the characterization and design of stable interfaces between nanoscale devices and cells.
PMID: 25889532 [PubMed - as supplied by publisher]
Associations between self-reported pest treatments and pesticide concentrations in carpet dust.
Environ Health. 2015;14(1):27
Authors: Deziel NC, Colt JS, Kent EE, Gunier RB, Reynolds P, Booth B, Metayer C, Ward MH
BACKGROUND: Recent meta-analyses demonstrate an association between self-reported residential pesticide use and childhood leukemia risk. Self-reports may suffer from recall bias and provide information only on broad pesticide categories. We compared parental self-reported home and garden pest treatments to pesticides measured in carpet dust.
METHODS: Parents of 277 children with leukemia and 306 controls in Northern and Central California (2001-2007) were asked about insect and weed treatments during the previous year. Carpet dust samples were analyzed for 47 pesticides. We present results for the 7 insecticides (carbaryl, propoxur, chlorpyrifos, diazinon, cyfluthrin, cypermethrin, permethrin), 5 herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], chlorthal, dicamba, mecoprop, simazine), and 1 synergist (piperonyl butoxide) that were present in home and garden products during the study period and were detected in ≥25% of carpet dust samples. We constructed linear regression models for the relative change in pesticide concentrations associated with self-reported treatment of pest types in cases and controls separately and combined, adjusting for demographics, housing characteristics, and nearby agricultural pesticide applications.
RESULTS: Several self-reported treatments were associated with pesticide concentrations in dust. For example, households with flea/tick treatments had 2.3 (95% Confidence Interval [CI]: 1.4, 3.7) times higher permethrin concentrations than households not reporting this treatment. Households reporting treatment for ants/cockroaches had 2.5 (95% CI: 1.5, 4.2) times higher cypermethrin levels than households not reporting this treatment. Weed treatment by a household member was associated with 1.9 (1.4, 2.6), 2.2 (1.6, 3.1), and 2.8 (2.1, 3.7) times higher dust concentrations of dicamba, mecoprop, and 2,4-D, respectively. Weed treatments by professional applicators were null/inversely associated with herbicide concentrations in dust. Associations were generally similar between cases and controls and were consistent with pesticide active ingredients in these products during the study time period.
CONCLUSIONS: Consistency between self-reported pest treatments, concentrations in dust, and pesticides in products lends credibility to the exposure assessment methods and suggests that differential recall by case-control status is minimal.
PMID: 25889489 [PubMed - as supplied by publisher]
The role of evidence and context for implementing a multimodal intervention to increase HIV testing.
Implement Sci. 2015;10(1):22
Authors: Bokhour BG, Saifu H, Goetz MB, Fix GM, Burgess J, Fletcher MD, Knapp H, Asch SM
BACKGROUND: Increasing the use of routine preventive care such as HIV testing is important, yet implementation of such evidence-based clinical care is complex. The Promoting Action on Research Implementation in Health Services (PARiHS) model for implementation posits that implementation will be most successful when the evidence, context, and facilitation strategies are strong for the clinical practice. We evaluated the relative importance of perceived evidence, context, and facilitation of HIV testing during the implementation of a multimodal intervention in US Department of Veterans Affairs primary care clinics.
METHODS: A multimodal intervention including clinical reminders (CRs), academic detailing-providing education sessions for providers-and social marketing to improve HIV testing was implemented in 15 VA primary care clinics in three regions. We conducted qualitative formative and process evaluations using semi-structured interviews with HIV lead clinicians, primary care lead clinicians, nurse managers, and social workers. Interviews were analyzed thematically to identify barriers and facilitators to implementation of HIV testing and how these were addressed by the intervention. Sites were then rated high, medium, or low on the dimensions of perceived evidence and the context for testing. We then assessed the relationship of these ratings to improvements in HIV testing rates found in earlier quantitative analyses.
RESULTS: Sites that showed greatest improvements in HIV testing rates also rated high on evidence and context. Conversely, sites that demonstrated the poorest improvements in testing rates rated low on both dimensions. Perceptions of evidence and several contextual aspects resulted in both barriers and facilitators to implementing testing. Evidence barriers included provider perceptions of evidence for routine testing as irrelevant to their population. Contextual barriers included clinical reminder overload, insufficient resources, onerous consent processes, stigma, provider discomfort, and concerns about linking individuals who test positive to HIV treatment. While most barriers were ameliorated by the intervention, HIV stigma in particular regions and concerns about linkage to care persisted.
CONCLUSIONS: Interventions to implement evidence-based practices such as HIV testing can be successful when utilizing proven quality improvement techniques. However, it is critical to address providers' perceptions of evidence and consider aspects of the local context in order to fully implement new routine clinical practices such as HIV testing.
PMID: 25889388 [PubMed - as supplied by publisher]
Updating emotional content in recovered depressed individuals: Evaluating deficits in emotion processing following a depressive episode.
J Behav Ther Exp Psychiatry. 2015 Mar 20;48:156-163
Authors: Levens SM, Gotlib IH
BACKGROUND AND OBJECTIVES: Previous research has demonstrated that depressed individuals have difficulty both disengaging from negative information and maintaining positive information in working memory (WM). The present study was conducted to examine whether the tendency for depressed individuals to maintain negative content in WM and to experience difficulties maintaining positive content in WM is due to negative mood (in)congruency effects during a depressive episode, or whether these tendencies are evident outside of a depressive episode.
METHODS: Individuals who had recovered from a depressive episode and never disordered controls performed emotion 0-back and 2-back tasks designed to assess biases in updating emotional content in working memory.
RESULTS: Similar to currently depressed individuals in previous studies, recovered depressed participants disengaged from happy stimuli more quickly and from sad stimuli more slowly than did their never-depressed counterparts.
LIMITATIONS: Despite the extension of a depression-specific finding to recovered depressed individuals, the present study does not test whether the identified emotion updating biases predict long-term relapse or recovery.
CONCLUSION: The obtained results suggest that a decreased ability to disengage from negative content and to maintain positive content in WM represents a trait-like cognitive style that impairs adaptive emotion regulation and may contribute to the recurrent nature of depression.
PMID: 25889375 [PubMed - as supplied by publisher]
Implementing highly specialized and evidence-based pediatric eating disorder treatment: protocol for a mixed methods evaluation.
Implement Sci. 2015;10(1):40
Authors: Couturier J, Kimber M, Lock J, Barwick M, McVey G, Findlay S, Webb C, Boettcher M, Niccols A, Woodford T
BACKGROUND: Eating disorders, which include anorexia nervosa and bulimia nervosa, are common in adolescent females and can have serious emotional and physical consequences, including death. Despite our knowledge about the severity of these illnesses, previous research indicates that adolescent patients are not receiving the best available treatment with fidelity. The main goal of this project is to reduce the knowledge gap between what research indicates is the best known treatment and what is actually delivered in clinical practice. Informed by the National Implementation Research Network model and the Consolidated Framework for Implementation Research meta-theory, our primary study aim is to increase the capacity of Ontario-based therapists to provide family-based treatment, by providing training and ongoing supervision.
METHODS/DESIGN: We will use a multi-site case study with a mixed method pre/post design to examine several implementation outcomes across four eating disorder treatment programs. We will provide a training workshop on family-based treatment as well as ongoing monthly supervision. In addition, we will assemble implementation teams at each site and coach them by phone on a monthly basis regarding any process issues. Our main outcomes include fidelity to the treatment model using quantitative evaluation of audio-recorded therapy sessions, as well as qualitative analysis of the perceptions of the implementation process using audio-recorded focus groups with all clinicians and administrators involved in the study.
DISCUSSION: To our knowledge, this is the first study to evaluate an implementation strategy for an evidence-based treatment for eating disorders. Challenges to date include obtaining ethics approval at all sites, and recruitment. This research will help to inform future studies on how to best implement evidence-based treatments in this field.
PMID: 25888744 [PubMed - as supplied by publisher]
Naive T Cell Maintenance and Function in Human Aging.
J Immunol. 2015 May 1;194(9):4073-4080
Authors: Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM
In studies of immune aging, naive T cells frequently take center stage. Describing the complexity of the human naive T cell repertoire remains a daunting task; however, emerging data suggest that homeostatic mechanisms are robust enough to maintain a large and diverse CD4 T cell repertoire with age. Compartment shrinkage and clonal expansions are challenges for naive CD8 T cells. In addition to population aspects, identification of potentially targetable cellular defects is receiving renewed interest. The last decade has seen remarkable progress in identifying genetic and biochemical pathways that are pertinent for aging in general and that are instructive to understand naive T cell dysfunction. One hallmark sets naive T cell aging apart from most other tissues except stem cells: they initiate but do not complete differentiation programs toward memory cells. Maintaining quiescence and avoiding differentiation may be the ultimate challenge to maintain the functions unique for naive T cells.
PMID: 25888703 [PubMed - as supplied by publisher]
Nomenclature of Toso, Fas Apoptosis Inhibitory Molecule 3, and IgM FcR.
J Immunol. 2015 May 1;194(9):4055-7
Authors: Kubagawa H, Carroll MC, Jacob CO, Lang KS, Lee KH, Mak T, McAndrews M, Morse HC, Nolan GP, Ohno H, Richter GH, Seal R, Wang JY, Wiestner A, Coligan JE
Hiromi Kubagawa and John E. Coligan coordinated an online meeting to define an appropriate nomenclature for the cell surface glycoprotein presently designated by different names: Toso, Fas apoptosis inhibitory molecule 3 (FAIM3), and IgM FcR (FcμR). FAIM3 and Faim3 are the currently approved symbols for the human and mouse genes, respectively, in the National Center for Biotechnology Information, Ensembl, and other databases. However, recent functional results reported by several groups of investigators strongly support a recommendation for renaming FAIM3/Faim3 as FCMR/Fcmr, a name better reflecting its physiological function as the FcR for IgM. Participants included 12 investigators involved in studying Toso/FAIM3(Faim3)/FμR, representatives from the Human Genome Nomenclature Committee (Ruth Seal) and the Mouse Genome Nomenclature Committee (Monica McAndrews), and an observer from the IgM research field (Michael Carroll). In this article, we provide a brief background of the key research on the Toso/FAIM3(Faim3)/FcμR proteins, focusing on the ligand specificity and functional activity, followed by a brief summary of discussion about adopting a single name for this molecule and its gene and a resulting recommendation for genome nomenclature committees.
PMID: 25888699 [PubMed - in process]
Comparison of Pain Score Reduction Using Triamcinolone vs. Betamethasone in Transforaminal Epidural Steroid Injections for Lumbosacral Radicular Pain.
Am J Phys Med Rehabil. 2015 Apr 16;
Authors: McCormick Z, Kennedy DJ, Garvan C, Rivers E, Temme K, Margolis S, Zander E, Rohr A, Smith MC, Plastaras C
OBJECTIVE: Although the comparative efficacy of particulate vs. nonparticulate steroids for the treatment of radicular pain with transforaminal epidural steroid injection has been investigated, there is minimal literature comparing particulate steroids. The authors aimed to determine whether transforaminal epidural steroid injection with triamcinolone or betamethasone, two particulate corticosteroids, more effectively reduces lumbosacral radicular pain.
DESIGN: This is a longitudinal cohort study of 1021 patients (1568 transforaminal epidural steroid injections) who received betamethasone or triamcinolone between January 2006 and October 2007 in an academic spine center. The frequency of greater than 50% pain reduction was compared between groups.
RESULTS: This study included 42.4% (433) male and 57.6% (588) female patients, with a mean (SD) age of 54.1 (16.7) yrs. Betamethasone and triamcinolone were used in 78.8% (1235) and 21.2% (333) of subjects, respectively. Significantly more patients who received triamcinolone (44.4% [95% confidence interval, 36.2%-52.8%]) experienced greater than 50% pain reduction at short-term follow-up (1-4 wks) compared with patients who received betamethasone (26.8% [95% confidence interval, 22.7%-31.4%]).
CONCLUSIONS: Patients who received transforaminal epidural steroid injection with triamcinolone reported more frequent pain relief of greater than 50% at short-term follow-up compared with those who received betamethasone. These findings further develop the literature on comparative effectiveness in epidural steroid injections. However, given the exploratory and retrospective nature of this investigation, further study is needed.
PMID: 25888660 [PubMed - as supplied by publisher]
A Secreted Effector Protein of Ustilago maydis Guides Maize Leaf Cells to Form Tumors.
Plant Cell. 2015 Apr 17;
Authors: Redkar A, Hoser R, Schilling L, Zechmann B, Krzymowska M, Walbot V, Doehlemann G
The biotrophic smut fungus Ustilago maydis infects all aerial organs of maize (Zea mays) and induces tumors in the plant tissues. U. maydis deploys many effector proteins to manipulate its host. Previously, deletion analysis demonstrated that several effectors have important functions in inducing tumor expansion specifically in maize leaves. Here, we present the functional characterization of the effector See1 (Seedling efficient effector1). See1 is required for the reactivation of plant DNA synthesis, which is crucial for tumor progression in leaf cells. By contrast, See1 does not affect tumor formation in immature tassel floral tissues, where maize cell proliferation occurs independent of fungal infection. See1 interacts with a maize homolog of SGT1 (Suppressor of G2 allele of skp1), a factor acting in cell cycle progression in yeast (Saccharomyces cerevisiae) and an important component of plant and human innate immunity. See1 interferes with the MAPK-triggered phosphorylation of maize SGT1 at a monocot-specific phosphorylation site. We propose that See1 interferes with SGT1 activity, resulting in both modulation of immune responses and reactivation of DNA synthesis in leaf cells. This identifies See1 as a fungal effector that directly and specifically contributes to the formation of leaf tumors in maize.
PMID: 25888589 [PubMed - as supplied by publisher]
Crowd-sourced assessment of surgical skills in cricothyrotomy procedure.
J Surg Res. 2015 Mar 18;
Authors: Aghdasi N, Bly R, White LW, Hannaford B, Moe K, Lendvay TS
BACKGROUND: Objective assessment of surgical skills is resource intensive and requires valuable time of expert surgeons. The goal of this study was to assess the ability of a large group of laypersons using a crowd-sourcing tool to grade a surgical procedure (cricothyrotomy) performed on a simulator. The grading included an assessment of the entire procedure by completing an objective assessment of technical skills survey.
MATERIALS AND METHODS: Two groups of graders were recruited as follows: (1) Amazon Mechanical Turk users and (2) three expert surgeons from University of Washington Department of Otolaryngology. Graders were presented with a video of participants performing the procedure on the simulator and were asked to grade the video using the objective assessment of technical skills questions. Mechanical Turk users were paid $0.50 for each completed survey. It took 10 h to obtain all responses from 30 Mechanical Turk users for 26 training participants (26 videos/tasks), whereas it took 60 d for three expert surgeons to complete the same 26 tasks.
RESULTS: The assessment of surgical performance by a group (n = 30) of laypersons matched the assessment by a group (n = 3) of expert surgeons with a good level of agreement determined by Cronbach alpha coefficient = 0.83.
CONCLUSIONS: We found crowd sourcing was an efficient, accurate, and inexpensive method for skills assessment with a good level of agreement to experts' grading.
PMID: 25888499 [PubMed - as supplied by publisher]
Cropped, Drosophila transcription factor AP-4, controls tracheal terminal branching and cell growth.
BMC Dev Biol. 2015 Apr 15;15(1):20
Authors: Wong MM, Liu MF, Chiu SK
BACKGROUND: Endothelial or epithelial cellular branching is vital in development and cancer progression; however, the molecular mechanisms of these processes are not clear. In Drosophila, terminal cell at the end of some tracheal tube ramifies numerous fine branches on the internal organs to supply oxygen. To discover more genes involved in terminal branching, we searched for mutants with very few terminal branches using the Kiss enhancer-trap line collection.
RESULTS: In this analysis, we identified cropped (crp), encoding the Drosophila homolog of the transcription activator protein AP-4. Overexpressing the wild-type crp gene or a mutant that lacks the DNA-binding region in either the tracheal tissues or terminal cells led to a loss-of-function phenotype, implying that crp can affect terminal branching. Unexpectedly, the ectopic expression of cropped also led to enlarged organs, and cell-counting experiments on the salivary glands suggest that elevated levels of AP-4 increase cell size and organ size. Like its mammalian counterpart, cropped is controlled by dMyc, as ectopic expression of dMyc in terminal cells increased cellular branching and the Cropped protein levels in vivo.
CONCLUSIONS: We find that the branching morphogenesis of terminal cells of the tracheal tubes in Drosophila requires the dMyc-dependent activation of Cropped/AP-4 protein to increase the cell growth of terminal cells.
PMID: 25888431 [PubMed - as supplied by publisher]
An evidence-based approach to identify aging-related genes in Caenorhabditis elegans.
BMC Bioinformatics. 2015;16(1):40
Authors: Callahan A, Cifuentes JJ, Dumontier M
BACKGROUND: Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate and analyze with existing databases and domain knowledge. To address this challenge, we demonstrate a scalable and effective approach for automatic evidence gathering and evaluation that leverages existing experimental data and literature-curated facts to identify genes involved in aging and lifespan regulation in C. elegans.
RESULTS: We developed a semantic knowledge base for aging by integrating data about C. elegans genes from WormBase with data about 2005 human and model organism genes from GenAge and 149 genes from GenDR, and with the Bio2RDF network of linked data for the life sciences. Using HyQue (a Semantic Web tool for hypothesis-based querying and evaluation) to interrogate this knowledge base, we examined 48,231 C. elegans genes for their role in modulating lifespan and aging. HyQue identified 24 novel but well-supported candidate aging-related genes for further experimental validation.
CONCLUSIONS: We use semantic technologies to discover candidate aging genes whose effects on lifespan are not yet well understood. Our customized HyQue system, the aging research knowledge base it operates over, and HyQue evaluations of all C. elegans genes are freely available at http://hyque.semanticscience.org .
PMID: 25888240 [PubMed - as supplied by publisher]
Cellular mechanisms of alveolar pathology in childhood interstitial lung diseases: current insights from mouse genetics.
Curr Opin Pediatr. 2015 Apr 17;
Authors: Kuo CS, Desai TJ
PURPOSE OF REVIEW: Childhood interstitial lung diseases (ILDs) are a diverse class of disorders affecting the alveolar gas exchange region that lack specific treatments and are usually fatal. Here, we integrate recent insights into alveolar cell biology with histopathology from well characterized mutations of surfactant-associated genes. We take a reductionist approach by parsing discrete histological features and correlating each to perturbation of a particular function of the alveolar epithelial type II (AT2) cell, the central driver of disease, to generate a working model for the cellular mechanisms of disease pathogenesis.
RECENT FINDINGS: The application of genetically modified mice and single cell genomics has yielded new insights into lung biology, including the identification of a bipotent alveolar progenitor in development, mapping of adult AT2 stem cells in vivo, and demonstration that latent cooperative interactions with fibroblasts can be pathologically activated by targeted injury of the AT2 cell.
SUMMARY: As we learn more about individual and cooperative roles for alveolar cells in health, we can dissect how perturbations of specific cellular functions contribute to disease in childhood ILDs. We hope our updated model centered around the AT2 cell as the initiator of disease provides a cellular framework that researchers can build upon and revise as they identify the specific molecular signals within and between alveolar cells that mediate the diverse pathologic features, so that targeted pharmacologic and cell-based treatments for patients can ultimately be engineered.
PMID: 25888154 [PubMed - as supplied by publisher]
Complementary and alternative medicine in pulmonology.
Curr Opin Pediatr. 2015 Apr 17;
Authors: Mark JD, Chung Y
PURPOSE OF REVIEW: To provide a comprehensive review of complementary and alternative medicine (CAM) therapies for the treatment of pulmonary disorders in children.
RECENT FINDINGS: The use of complementary medicine (CAM) is commonly used by both children and adults with breathing problems, and especially in chronic pulmonary disorders such as asthma and cystic fibrosis. Many clinics and hospitals now offer CAM, even though most of the conventionally trained health practitioners have little knowledge or education regarding CAM therapies. Research in CAM that demonstrates overall benefit is lacking, especially in children. Often parents do not report CAM use to their child's healthcare provider and this could compromise their overall quality of care. Although many research studies evaluating CAM therapies have methodological flaws, data exist to support CAM therapies in treating children with pulmonary disorders.
SUMMARY: This review examines the latest evidence of CAM use and effectiveness in children with pulmonary disorders. Physicians should be aware of the many CAM therapy options and the research surrounding them in order to provide their patients with the most current and accurate information available.
PMID: 25888149 [PubMed - as supplied by publisher]
Recent advances in cystic fibrosis.
Curr Opin Pediatr. 2015 Apr 17;
Authors: Milla CE, Moss RB
PURPOSE OF REVIEW: The field of cystic fibrosis (CF) continues to evolve at a fast pace thanks to novel observations that have enabled deeper understanding of the disease pathophysiology. Parallel groundbreaking developments in innovative therapies permit, for the first time, distinct disease modification.
RECENT FINDINGS: This review highlights important discoveries in fluid homeostasis and mucus secretion in CF that further informs the pathophysiology of the airway disease that characterizes CF. In addition, current concepts and novel paradigms, such as 'theratypes' and 'CF transmembrane conductance regulator chaperome', which will be important for the continued development of disease modifying therapies, are reviewed.
SUMMARY: The rate of progress in the field continues to accelerate with new knowledge informing the development of innovative therapies. This has already led to tangible substantial and unprecedented clinical benefit for selected subsets of the CF patient population. In the years ahead, further knowledge acquisition may motivate the extension of these benefits to the larger population of people with CF.
PMID: 25888148 [PubMed - as supplied by publisher]
The pediatric microbiome and the lung.
Curr Opin Pediatr. 2015 Apr 17;
Authors: Tracy M, Cogen J, Hoffman LR
PURPOSE OF REVIEW: Many pediatric lung diseases are characterized by infection. These infections are generally diagnosed, studied, and treated using standard culture methods to identify 'traditional pathogens'. Based on these techniques, healthy lungs have generally been thought to be sterile. However, recent advances in culture-independent microbiological techniques challenge this paradigm by identifying diverse microbes in respiratory specimens (respiratory microbiomes) from both healthy people and those with diverse lung diseases. In addition, growing evidence suggests a link between gastrointestinal microbiomes and inflammatory diseases of various mucosal surfaces, including airways.
RECENT FINDINGS: This article reviews the rapidly developing field of respiratory microbiome research, emphasizing recent progress made employing increasingly sophisticated technologies. Although many of the relevant studies have focused on adults with cystic fibrosis, recent research has included children and adults with other respiratory diseases, as well as healthy individuals. These studies suggest that even healthy children have airway microbiomes, and that both respiratory and gastrointestinal microbiomes often differ between healthy people and those with different types and severities of airway disease. The causal relationships between microbiomes, disease type and progression, and treatments such as antibiotics must now be defined.
SUMMARY: The advent of culture-independent microbiological techniques has transformed how we think about the relationship between microbes and airway disease. More research is required to translate these findings to improved therapies and preventive strategies.
PMID: 25888147 [PubMed - as supplied by publisher]
Characterization of the enhancement of zero valent iron on microbial azo reduction.
BMC Microbiol. 2015 Apr 10;15(1):85
Authors: Fang Y, Xu M, Wu WM, Chen X, Sun G, Guo J, Liu X
BACKGROUND: The microbial method for the treatment of azo dye is promising, but the reduction of azo dye is the rate-limiting step. Zero valent iron (Fe(0)) can enhance microbial azo reduction, but the interactions between microbes and Fe(0) and the potential mechanisms of enhancement remain unclear. Here, Shewanella decolorationis S12, a typical azo-reducing bacterium, was used to characterize the enhancement of Fe(0) on microbial decolorization.
RESULTS: The results indicated that anaerobic iron corrosion is a key inorganic chemical process in which OH(-), H2, and Fe(2+) are produced. Once Fe(0) was added to the microbial azo reduction system, the proper pH for microbial azo reduction was maintained by OH(-), and H2 served as the favored electron donor for azo respiration. Subsequently, the bacterial biomass yield and viability significantly increased. Following the corrosion of Fe(0), nanometer-scale Fe precipitates were adsorbed onto cell surfaces and even accumulated inside cells as observed by transmission electron microscope energy dispersive spectroscopy (TEM-EDS).
CONCLUSIONS: A conceptual model for Fe(0)-assisted azo dye reduction by strain S12 was established to explain the interactions between microbes and Fe(0) and the potential mechanisms of enhancement. This model indicates that the enhancement of microbial azo reduction in the presence of Fe(0) is mainly due to the stimulation of microbial growth and activity by supplementation with elemental iron and an additional electron donor. This study has expanded our knowledge of the enhancement of microbial azo reduction by Fe(0) and laid a foundation for the development of Fe(0)-microbial integrated azo dye wastewater treatment technology.
PMID: 25888062 [PubMed - as supplied by publisher]
MicroRNA-mediated Regulation of Differentiation and Trans-differentiation in Stem Cells.
Adv Drug Deliv Rev. 2015 Apr 14;
Authors: Ong SG, Lee WH, Kodo K, Wu JC
MicroRNAs (miRNAs) are key components of a broadly conserved post-transcriptional mechanism that controls gene expression by targeting mRNAs. miRNAs regulate diverse biological processes, including the growth and differentiation of stem cells as well as the regulation of both endogenous tissue repair that has critical implications in the development of regenerative medicine approaches. In this review, we first describe key features of miRNA biogenesis and their role in regulating self-renewal, and then discuss the involvement of miRNAs in the determination of cell fate decisions. We highlight the role of miRNAs in the emergent field of reprogramming and trans-differentiation of somatic cells that could further our understanding of miRNA biology and regenerative medicine applications. Finally, we describe potential techniques for proper delivery of miRNAs in target cells.
PMID: 25887992 [PubMed - as supplied by publisher]
Infusion pump-mediated mechanical hemolysis in pediatric patients.
Ann Clin Lab Sci. 2015 Mar;45(2):140-7
Authors: Hughes J, McNaughton J, Andrews J, George T, Bergero C, Pyke-Grimm K, Galel SA, Gonzalez C, Goodnough LT, Fontaine MJ
CONTEXT: Hemoglobinuria was observed after packed red blood cell transfusion in a series of patients at our pediatric treatment center. Laboratory testing was suggestive of intravascular hemolysis with no support for an immunohematologic process.
OBJECTIVE: We investigated these adverse events to define a quality improvement plan and to prevent future hemolytic adverse events. Multiple factors were investigated, and the only change identified was the implementation of a new infusion pump (Pump A) that replaced a previous model (Pump B).
DESIGN: In vitro pump analyses, a retrospective review of urinalyses, and prospective urinalysis and nursing surveillances were also performed.
RESULTS: In in vitro analysis of the pumps, irradiated units with higher hematocrit at a low flow rate through Pump A had a greater than thirty-fold increase in free hemoglobin from baseline compared to minimal free hemoglobin changes seen with Pump B. Irradiated units with a lower hematocrit had a minimal change in free hemoglobin from baseline with both Pumps A and B at either low or high flow rate. Subsequently, only units with lower hematocrits were issued for transfusion of pediatric patients, and Pump A was replaced by Pump B in the outpatient unit. Retrospective and prospective surveillances found no additional unexplained cases of gross hemoglobinuria associated with transfusion.
CONCLUSION: The investigation determined that infusion of higher hematocrit units using a specific commercial pump was associated with mechanical hemolysis. The change to units with lower hematocrit through an alternative pump has been an effective corrective action to date.
PMID: 25887866 [PubMed - in process]
PRAME Immunohistochemical Staining in Transient Abnormal Myelopoiesis and Myeloid Leukemia Associated with Down Syndrome.
Ann Clin Lab Sci. 2015 Mar;45(2):121-7
Authors: Chisholm KM, Rivetta CV, Heerema-McKenney A
Transient abnormal myelopoiesis (TAM) and myeloid leukemia associated with Down syndrome (ML of DS) have morphologically indistinguishable blasts. TAM usually presents and regresses within the first three months of life. In a subset of patients, myelopoiesis remains abnormal, and the persistence of elevated blasts after 6 months is considered ML of DS. Current tools including cytogenetics and flow cytometry fail to distinguish blasts of TAM that will regress from blasts of ML of DS. One gene expression profiling study suggested PRAME expression was significantly increased in ML of DS compared to TAM. To further investigate this finding, we studied PRAME protein expression by immunohistochemistry in cases of TAM and ML of DS. PRAME immunoreactivity was found in blasts, dysplastic megakaryocytes, and fibroblasts. Four cases of TAM and fourteen cases of ML of DS had interpretable staining, with PRAME cytoplasmic reactivity in megakaryoblasts. Of the four cases of TAM, two were positive for PRAME; of the two patients, one had follow-up demonstrating ML of DS and the other had fully regressing TAM. Of the fourteen cases of ML of DS, ten had at least a subset of cells with positive PRAME staining, while four were negative for PRAME. In summary, PRAME immunoreactivity in ML of DS is largely due to the non-blast components, while PRAME immunoreactivity in blasts of TAM is not restricted to cases that progress to ML of DS.
PMID: 25887863 [PubMed - in process]
Non-invasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing.
Blood. 2015 Apr 17;
Authors: Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, Takahashi K, Glover C, Keane C, Kihira S, Visser B, Callahan J, Kong KA, Faham M, Corbelli KS, Miklos D, Advani RH, Levy R, Hicks RJ, Hertzberg M, Ohgami RS, Gandhi MK, Diehn M, Alizadeh AA
Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease by immunoglobulin high-throughput sequencing (Ig-HTS) from peripheral blood provides an alternate strategy for surveillance. We prospectively evaluated the utility of Ig-HTS within 311 blood and 105 tumor samples from 75 patients with DLBCL, comparing Ig-HTS from the cellular (circulating leukocytes) and acellular (plasma cell-free DNA) compartments of peripheral blood to clinical outcomes and 18FDG PET/CT (n=173). Clonotypic immunoglobulin rearrangements were detected in 83% of patients with adequate tumor samples to enable subsequent monitoring in peripheral blood. Molecular disease measured from plasma, as compared to circulating leukocytes, was more abundant and more correlated with radiographic disease burden. Prior to treatment, molecular disease was detected in the plasma of 82% of patients compared to 71% in circulating cells (p=0.68). However, molecular disease was detected significantly more frequently in the plasma at time of relapse (100% vs. 30%; p = 0.001). Detection of molecular disease in the plasma often preceded PET/CT detection of relapse in patients initially achieving remission. During surveillance time-points prior to relapse, plasma Ig-HTS demonstrated improved specificity (100% vs. 56%, p<0.0001) and similar sensitivity (31% vs. 55%, p=0.4) compared to PET/CT. Given its high specificity, Ig-HTS from plasma has potential clinical utility for surveillance after complete remission.
PMID: 25887775 [PubMed - as supplied by publisher]
Unraveling the 3D genome: genomics tools for multiscale exploration.
Trends Genet. 2015 Apr 14;
Authors: Risca VI, Greenleaf WJ
A decade of rapid method development has begun to yield exciting insights into the 3D architecture of the metazoan genome and the roles it may play in regulating transcription. Here we review core methods and new tools in the modern genomicist's toolbox at three length scales, ranging from single base pairs to megabase-scale chromosomal domains, and discuss the emerging picture of the 3D genome that these tools have revealed. Blind spots remain, especially at intermediate length scales spanning a few nucleosomes, but thanks in part to new technologies that permit targeted alteration of chromatin states and time-resolved studies, the next decade holds great promise for hypothesis-driven research into the mechanisms that drive genome architecture and transcriptional regulation.
PMID: 25887733 [PubMed - as supplied by publisher]
Identifying multi-locus chromatin contacts in human cells using tethered multiple 3C.
BMC Genomics. 2015;16(1):121
Authors: Ay F, Vu TH, Zeitz MJ, Varoquaux N, Carette JE, Vert JP, Hoffman AR, Noble WS
BACKGROUND: Several recently developed experimental methods, each an extension of the chromatin conformation capture (3C) assay, have enabled the genome-wide profiling of chromatin contacts between pairs of genomic loci in 3D. Especially in complex eukaryotes, data generated by these methods, coupled with other genome-wide datasets, demonstrated that non-random chromatin folding correlates strongly with cellular processes such as gene expression and DNA replication.
RESULTS: We describe a genome architecture assay, tethered multiple 3C (TM3C), that maps genome-wide chromatin contacts via a simple protocol of restriction enzyme digestion and religation of fragments upon agarose gel beads followed by paired-end sequencing. In addition to identifying contacts between pairs of loci, TM3C enables identification of contacts among more than two loci simultaneously. We use TM3C to assay the genome architectures of two human cell lines: KBM7, a near-haploid chronic leukemia cell line, and NHEK, a normal diploid human epidermal keratinocyte cell line. We confirm that the contact frequency maps produced by TM3C exhibit features characteristic of existing genome architecture datasets, including the expected scaling of contact probabilities with genomic distance, megabase scale chromosomal compartments and sub-megabase scale topological domains. We also confirm that TM3C captures several known cell type-specific contacts, ploidy shifts and translocations, such as Philadelphia chromosome formation (Ph+) in KBM7. We confirm a subset of the triple contacts involving the IGF2-H19 imprinting control region (ICR) using PCR analysis for KBM7 cells. Our genome-wide analysis of pairwise and triple contacts demonstrates their preference for linking open chromatin regions to each other and for linking regions with higher numbers of DNase hypersensitive sites (DHSs) to each other. For near-haploid KBM7 cells, we infer whole genome 3D models that exhibit clustering of small chromosomes with each other and large chromosomes with each other, consistent with previous studies of the genome architectures of other human cell lines.
CONCLUSION: TM3C is a simple protocol for ascertaining genome architecture and can be used to identify simultaneous contacts among three or four loci. Application of TM3C to a near-haploid human cell line revealed large-scale features of chromosomal organization and multi-way chromatin contacts that preferentially link regions of open chromatin.
PMID: 25887659 [PubMed - as supplied by publisher]
Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies.
BMC Genet. 2015;16(1):34
Authors: Wojcik GL, Kao WH, Duggal P
BACKGROUND: Despite the success of genome-wide association studies (GWAS), there still remains "missing heritability" for many traits. One contributing factor may be the result of examining one marker at a time as opposed to a group of markers that are biologically meaningful in aggregate. To address this problem, a variety of gene- and pathway-level methods have been developed to identify putative biologically relevant associations. A simulation was conducted to systematically assess the performance of these methods. Using genetic data from 4,500 individuals in the Wellcome Trust Case Control Consortium (WTCCC), case-control status was simulated based on an additive polygenic model. We evaluated gene-level methods based on their sensitivity, specificity, and proportion of false positives. Pathway-level methods were evaluated on the relationship between proportion of causal genes within the pathway and the strength of association.
RESULTS: The gene-level methods had low sensitivity (20-63%), high specificity (89-100%), and low proportion of false positives (0.1-6%). The gene-level program VEGAS using only the top 10% of associated single nucleotide polymorphisms (SNPs) within the gene had the highest sensitivity (28.6%) with less than 1% false positives. The performance of the pathway-level methods depended on their reliance upon asymptotic distributions or if significance was estimated in a competitive manner. The pathway-level programs GenGen, GSA-SNP and MAGENTA had the best performance while accounting for potential confounders.
CONCLUSIONS: Novel genes and pathways can be identified using the gene and pathway-level methods. These methods may provide valuable insight into the "missing heritability" of traits and provide biological interpretations to GWAS findings.
PMID: 25887572 [PubMed - as supplied by publisher]
The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial.
Clin J Am Soc Nephrol. 2015 Apr 17;
Authors: Floege J, Kubo Y, Floege A, Chertow GM, Parfrey PS
BACKGROUND AND OBJECTIVES: Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug.
RESULTS: Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%-7% at any one time point in patients in whom CUA was not reported.
CONCLUSION: Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.
PMID: 25887067 [PubMed - as supplied by publisher]
Rates and Predictors of Newly Diagnosed HIV infection among Veterans Receiving Routine Once-Per-Lifetime HIV Testing in the Veterans Health Administration.
J Acquir Immune Defic Syndr. 2015 Apr 15;
Authors: Goetz MB, Hoang T, Kan VL, Rimland D, Rodriguez-Barradas MC, Asch SM
OBJECTIVE: To determine predictors and variations in the rate of newly diagnosed HIV infection among persons who underwent routine (i.e., non-risk based) rather than risk-based HIV testing in Veterans Health Administration (VHA) facilities.
METHODS: Retrospective, observational study of the HIV infection new rates during the period when VHA policy called for routine (2009-2012) versus risk-based (2006-2009) HIV testing. Source data for testing results at 18 VHA facilities were obtained from the VHA National Corporate Data Warehouse.
RESULTS: New HIV diagnoses were established in 0.14% (95% CI, 0.12 - 0.46%) of the 210,957 patients tested in the routine-testing period versus 0.46% (95% CI, 0.42 - 1.29%) of the 89,652 patients tested in the risk-based testing period. Among persons 65-74 and ≥75 years of age the new diagnosis rates were 0.07% (95% CI, 0.04% - 0.09%) and 0.02% (95% CI, 0.00 - 0.03%), respectively and thus less than the generally accepted cost-effective threshold of 0.10%. Among African-Americans the upper bound of the 95% confidence interval of the crude rate of new diagnoses during the routine testing period was greater than 0.1% across all age strata. When assessed by year of testing the adjusted rates of new diagnoses fell from 0.20% in 2010 to 0.10% in 2012 CONCLUSIONS:: Routine HIV testing is cost-effective among persons less than 65 years of age. Among older patients, risk-based testing may be a more efficient and cost-effective approach. This will be increasingly relevant if rates of new HIV diagnoses in persons undergoing routine testing continue to decrease.
PMID: 25886931 [PubMed - as supplied by publisher]
A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.
Bone. 2015 Apr 14;
Authors: Guenther CA, Wang Z, Li E, Tran MC, Logan CY, Nusse R, Pantalena-Filho L, Yang GP, Kingsley DM
Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals.
PMID: 25886903 [PubMed - as supplied by publisher]
Measuring semantic similarities by combining gene ontology annotations and gene co-function networks.
BMC Bioinformatics. 2015;16(1):44
Authors: Peng J, Uygun S, Kim T, Wang Y, Rhee SY, Chen J
BACKGROUND: Gene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms.
RESULTS: We introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstrate that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families.
CONCLUSIONS: Using NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited. Supplementary information and software are available at http://www.msu.edu/~jinchen/NETSIM .
PMID: 25886899 [PubMed - as supplied by publisher]
Higher Vagal Activity as Related to Survival in Patients With Advanced Breast Cancer: An Analysis of Autonomic Dysregulation.
Psychosom Med. 2015 Apr 16;
Authors: Giese-Davis J, Wilhelm FH, Tamagawa R, Palesh O, Neri E, Taylor CB, Kraemer HC, Spiegel D
OBJECTIVE: High levels of high-frequency heart rate variability (HF-HRV), related to parasympathetic-nervous-system functioning, have been associated with longer survival in patients with myocardial infarction and acute trauma and in patients undergoing palliative care. From animal studies linking higher vagal activity with better immune system functioning and reduced metastases, we hypothesized that higher HF-HRV would predict longer survival in patients with metastatic or recurrent breast cancer (MRBC).
METHODS: Eighty-seven patients with MRBC participated in a laboratory task including a 5-minute resting baseline electrocardiogram. HF-HRV was computed as the natural logarithm of the summed power spectral density of R-R intervals (0.15-0.50 Hz). In this secondary analysis of a study testing whether diurnal cortisol slope predicted survival, we tested the association between resting baseline HF-HRV on survival using Cox proportional hazards models.
RESULTS: A total of 50 patients died during a median follow-up of 7.99 years. Higher baseline HF-HRV predicted significantly longer survival, with a hazard ratio of 0.75 (95% confidence interval = 0.60-0.92, p = .006). Visceral metastasis status and baseline heart rate were related to both HF-HRV and survival. However, a combination of HF-HRV and heart rate further improved survival prediction, with a hazard ratio of 0.64 (95% confidence interval = 0.48-0.85, p = .002).
CONCLUSIONS: Vagal activity of patients with MRBC strongly predicted their survival, extending the known predictive window of HF-HRV in cancer beyond palliative care. Vagal activity can be altered by behavioral, pharmacological, and surgical interventions and may be a promising target for extending life expectancy in patients with metastasizing cancer.
PMID: 25886831 [PubMed - as supplied by publisher]
Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment.
Ann Thorac Surg. 2015 Apr 15;
Authors: Yang CF, Meyerhoff RR, Stephens SJ, Singhapricha T, Toomey CB, Anderson KL, Kelsey C, Harpole D, D'Amico TA, Berry MF
BACKGROUND: Salvage surgical resection for non-small cell lung cancer (NSCLC) patients initially treated with definitive chemotherapy and radiotherapy can be performed safely, but the long-term benefits are not well characterized.
METHODS: Perioperative complications and long-term survival of all patients with NSCLC who received curative-intent definitive radiotherapy, with or without chemotherapy, followed by lobectomy from 1995 to 2012 were evaluated.
RESULTS: During the study period, 31 patients met the inclusion criteria. Clinical stage distribution was stage I in 2 (6%), stage II in 5 (16%), stage IIIA in 15 (48%), stage IIIB in 5 (16%), stage IV in 3 (10%), and unknown in 1 (3%). The reasons surgical resection was initially not considered were: patients deemed medically inoperable (5 [16%]); extent of disease was considered unresectable (21 [68%]); small cell lung cancer misdiagnosis (1 [3%]), and unknown (4 [13%]). Definitive therapy was irradiation alone in 2 (6%), concurrent chemoradiotherapy in 28 (90%), and sequential chemoradiotherapy in 1 (3%). The median radiation dose was 60 Gy. Patients were subsequently referred for resection because of obvious local relapse, medical tolerance of surgical intervention, or posttherapy imaging suggesting residual disease. The median time from radiation to lobectomy was 17.7 weeks. There were no perioperative deaths, and morbidity occurred in 15 patients (48%). None of the 3 patients with residual pathologic nodal disease survived longer than 37 months, but the 5-year survival of pN0 patients was 36%. Patients who underwent lobectomy for obvious relapse (n = 3) also did poorly, with a median overall survival of 9 months.
CONCLUSIONS: Lobectomy after definitive radiotherapy can be done safely and is associated with reasonable long-term survival, particularly when patients do not have residual nodal disease.
PMID: 25886806 [PubMed - as supplied by publisher]
Future of Anesthesiology Is Perioperative Medicine: A Call for Action.
Anesthesiology. 2015 Apr 20;
Authors: Kain ZN, Fitch JC, Kirsch JR, Mets B, Pearl RG
PMID: 25886775 [PubMed - as supplied by publisher]
Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring.
Genome Biol. 2015;16(1):28
Authors: Case LK, Wall EH, Osmanski EE, Dragon JA, Saligrama N, Zachary JF, Lemos B, Blankenhorn EP, Teuscher C
BACKGROUND: The prevalence of some autoimmune diseases is greater in females compared with males, although disease severity is often greater in males. The reason for this sexual dimorphism is unknown, but it may reflect negative selection of Y chromosome-bearing sperm during spermatogenesis or male fetuses early in the course of conception/pregnancy. Previously, we showed that the sexual dimorphism in experimental autoimmune encephalomyelitis (EAE) is associated with copy number variation (CNV) in Y chromosome multicopy genes. Here, we test the hypothesis that CNV in Y chromosome multicopy genes influences the paternal parent-of-origin effect on EAE susceptibility in female mice.
RESULTS: We show that C57BL/6 J consomic strains of mice possessing an identical X chromosome and CNV in Y chromosome multicopy genes exhibit sperm head abnormalities and female-biased sex ratio. This is consistent with X-Y intragenomic conflict arising from an imbalance in CNV between homologous X:Y chromosome multicopy genes. These males also display paternal transmission of EAE to female offspring and differential loading of microRNAs within the sperm nucleus. Furthermore, in humans, families of probands with multiple sclerosis similarly exhibit a female-biased sex ratio, whereas families of probands affected with non-sexually dimorphic autoimmune diseases exhibit unbiased sex ratios.
CONCLUSIONS: These findings provide evidence for a mechanism at the level of the male gamete that contributes to the sexual dimorphism in EAE and paternal parent-of-origin effects in female mice, raising the possibility that a similar mechanism may contribute to the sexual dimorphism in multiple sclerosis.
PMID: 25886764 [PubMed - as supplied by publisher]
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