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Other Publications (286)
- Asian Journal of Endoscopic Surgery
- Hand (New York, N.Y.)
- Iranian Journal of Public Health
- BMC Medical Genetics
- Bioresource Technology
- Nature Methods
- Macromolecular Rapid Communications
- International Journal of Environmental Research and Public Health
- Lab on a Chip
- The American Journal of Tropical Medicine and Hygiene
- Acta Anaesthesiologica Taiwanica : Official Journal of the Taiwan Society of Anesthesiologists
- Chemical Communications (Cambridge, England)
- Journal of Agricultural and Food Chemistry
- Circulation
- Evidence-based Complementary and Alternative Medicine : ECAM
- Endocrine Journal
- PloS One
- PloS One
- Journal of Biomedical Science
- Molecular BioSystems
- Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology
- Biochemical and Biophysical Research Communications
- Lab on a Chip
- Current Cardiology Reports
- Hu Li Za Zhi The Journal of Nursing
- Lab on a Chip
- International Journal of Oncology
- Chemical & Pharmaceutical Bulletin
- Atherosclerosis
- Journal of the European Academy of Dermatology and Venereology : JEADV
- Environmental Research
- Virology
- Small (Weinheim an Der Bergstrasse, Germany)
- Archives of Ophthalmology
- Pacing and Clinical Electrophysiology : PACE
- Disability and Rehabilitation
- Journal of the Chinese Medical Association : JCMA
- Journal of Nanoscience and Nanotechnology
- Molecular Ecology
- BMJ Open
- Endocrinology
- Developmental Neurorehabilitation
- Progress in Biophysics and Molecular Biology
- Nanoscale
- Journal of Immigrant and Minority Health / Center for Minority Public Health
- Sensors (Basel, Switzerland)
- Progress in Biophysics and Molecular Biology
- Global Public Health
- Blood
- Physical Review Letters
- Dalton Transactions (Cambridge, England : 2003)
- Journal of the American Geriatrics Society
- Biology of Reproduction
- Journal of Clinical Nursing
- Singapore Medical Journal
- American Journal of Health Behavior
- PloS One
- Chemical Communications (Cambridge, England)
- Journal of Hypertension
- Environmental Science and Pollution Research International
- PloS One
- Indian Pacing and Electrophysiology Journal
- ACS Applied Materials & Interfaces
- Diabetes Research and Clinical Practice
- Journal of AAPOS : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus
- Journal of Neurotrauma
- Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
- Plastic and Reconstructive Surgery
- Journal of Biomedical Science
- British Journal of Cancer
- The Gerontologist
- Journal of Vascular and Interventional Radiology : JVIR
- Environmental Health and Preventive Medicine
- Journal of the American Chemical Society
- The Journal of Chemical Physics
- Journal of Food Protection
- Brain Pathology (Zurich, Switzerland)
- Journal of Drugs in Dermatology : JDD
- The Journal of Physical Chemistry. B
- Journal of Bacteriology
- Annals of Plastic Surgery
- Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
- Optics Letters
- American Journal of Rhinology & Allergy
- Endoscopy
- Journal of Natural Medicines
- Journal of Clinical Immunology
- Journal of Radiation Research
- Toxicology Mechanisms and Methods
- Organic Letters
- Dental Materials Journal
- Chemical & Pharmaceutical Bulletin
- The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science
- Journal of the Renin-angiotensin-aldosterone System : JRAAS
- Bioanalysis
- Future Oncology (London, England)
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Neuropsychiatric Disease and Treatment
- Bioanalysis
- Journal of Advanced Nursing
- Congestive Heart Failure (Greenwich, Conn.)
- Journal of Cardiovascular Electrophysiology
- PloS One
- Medical Image Computing and Computer-assisted Intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
- PLoS Genetics
- Evidence-based Complementary and Alternative Medicine : ECAM
- Biopolymers
- Advanced Functional Materials
- Journal of Ginseng Research
- Pacing and Clinical Electrophysiology : PACE
- Archives of Oral Biology
- Hepatology (Baltimore, Md.)
- Gait & Posture
- The Canadian Journal of Cardiology
- Research in Developmental Disabilities
- Behavioural Brain Research
- The American Journal of Emergency Medicine
- Pharmaceutical Research
- Chemical Reviews
- Letters in Applied Microbiology
- Veterinary Parasitology
- Journal of Gastroenterology and Hepatology
- Renal Failure
- European Journal of Pediatrics
- The American Journal of Sports Medicine
- Pharmacology
- Respirology (Carlton, Vic.)
- Clinical and Experimental Immunology
- Bioorganic & Medicinal Chemistry Letters
- Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry
- Journal of the American Society of Nephrology : JASN
- Bioorganic & Medicinal Chemistry Letters
- Thrombosis and Haemostasis
- Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]
- Cancer Letters
- Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society
- The Journal of Hand Surgery
- American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists
- Critical Care Medicine
- The Journal of General Physiology
- Molecular and Cellular Endocrinology
- International Anesthesiology Clinics
- Water Research
- The Journal of General Virology
- Chemical Communications (Cambridge, England)
- PLoS Genetics
- Nursing & Health Sciences
- Molecular BioSystems
- Parasitology Research
- Chemistry, an Asian Journal
- PloS One
- Environmental Health Perspectives
- Journal of Clinical Nursing
- Journal of Pharmaceutical and Biomedical Analysis
- Bioresource Technology
- Journal of Virological Methods
- Journal of Neurological Surgery. Part A, Central European Neurosurgery
- Tetrahedron Letters
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Hepatology (Baltimore, Md.)
- JACC. Cardiovascular Imaging
- Public Health Nutrition
- The Canadian Journal of Cardiology
- The Journal of Surgical Research
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- PloS One
- Proceedings of the National Academy of Sciences of the United States of America
- Lab on a Chip
- Journal of AAPOS : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- BMJ Case Reports
- Neuropsychiatric Disease and Treatment
- Bioorganic & Medicinal Chemistry Letters
- PloS One
- The Journal of Investigative Dermatology
- Nature Reviews. Cardiology
- PLoS Genetics
- Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
- Proceedings of the National Academy of Sciences of the United States of America
- Emerging Health Threats Journal
- Breast Cancer Research and Treatment
- American Journal of Hypertension
- PloS One
- Surgical Laparoscopy, Endoscopy & Percutaneous Techniques
- Circulation. Arrhythmia and Electrophysiology
- Expert Opinion on Investigational Drugs
- Langmuir : the ACS Journal of Surfaces and Colloids
- Global Health Action
- Dalton Transactions (Cambridge, England : 2003)
- Internal Medicine (Tokyo, Japan)
- Fertility and Sterility
- Psycho-oncology
- ChemSusChem
- Journal of Biochemistry
- Nature Communications
- Journal of Controlled Release : Official Journal of the Controlled Release Society
- International Journal of Molecular Sciences
- Parasitology Research
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Langmuir : the ACS Journal of Surfaces and Colloids
- Radiation Oncology (London, England)
- Biochimica Et Biophysica Acta
- Vox Sanguinis
- Blood
- Journal of Dairy Science
- Journal of Hypertension
- Journal of Molecular Biology
- Heart (British Cardiac Society)
- PLoS Genetics
- Lab on a Chip
- Neuromolecular Medicine
- Biochimica Et Biophysica Acta
- International Journal of Molecular Sciences
- Chemistry (Weinheim an Der Bergstrasse, Germany)
- Acta Ophthalmologica
- Clinical Chemistry
- Diabetes & Metabolic Syndrome
- Medicinal Chemistry (Shariqah (United Arab Emirates))
- Nutrition (Burbank, Los Angeles County, Calif.)
- Journal of AAPOS : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus
- Health Physics
- Inflammatory Bowel Diseases
- Organic & Biomolecular Chemistry
- Environmental Science and Pollution Research International
- Plastic and Reconstructive Surgery
- PLoS Genetics
- Methods in Molecular Biology (Clifton, N.J.)
- Hernia : the Journal of Hernias and Abdominal Wall Surgery
- Circulation
- IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
- The American Journal of Gastroenterology
- The Laryngoscope
- Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
- The Journal of Chemical Physics
- Gynecologic Oncology
- Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
- PloS One
- NeuroImage
- The American Journal of Hospice & Palliative Care
- Journal of Medical Virology
- Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health
- Talanta
- Analytica Chimica Acta
- Asian Journal of Endoscopic Surgery
- Neurology
- Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society
- Western Journal of Nursing Research
- Asian Pacific Journal of Cancer Prevention : APJCP
- Journal of AAPOS : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus
- Environmental Research
- The Journal of Investigative Dermatology
- PloS One
- PeerJ
- The Journal of Biological Chemistry
- Biosecurity and Bioterrorism : Biodefense Strategy, Practice, and Science
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Bioresource Technology
- Nanoscale
- Evidence-based Complementary and Alternative Medicine : ECAM
- International Journal for Parasitology
- BMJ Open
- American Journal of Public Health
- Veterinary Microbiology
- Cellular and Molecular Life Sciences : CMLS
- World Journal of Gastroenterology : WJG
- Biochimica Et Biophysica Acta
- Hypertension
- Chemical Communications (Cambridge, England)
- Macromolecular Bioscience
- Anesthesiology Clinics
- Seminars in Respiratory and Critical Care Medicine
- Development (Cambridge, England)
- Journal of Virology
- Journal of Mass Spectrometry : JMS
- American Journal of Translational Research
- Mayo Clinic Proceedings. Mayo Clinic
- Journal of the American Heart Association
- Journal of Gastroenterology
- Journal of the International Association of Providers of AIDS Care
- Applied Optics
- Angiogenesis
- Annals of Surgical Oncology
- The Review of Scientific Instruments
- Research in Developmental Disabilities
- Lab on a Chip
- Molecular and Cellular Biology
Articles by Victoria W. K. Tung in JoVE
Other articles by Victoria W. K. Tung on PubMed
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Single Channel Layer, Single Sheath-flow Inlet Microfluidic Flow Cytometer with Three-dimensional Hydrodynamic Focusing
Lab on a Chip.
Sep, 2012 |
Pubmed ID: 22763751 Flow cytometry is a technique capable of optically characterizing biological particles in a high-throughput manner. In flow cytometry, three dimensional (3D) hydrodynamic focusing is critical for accurate and consistent measurements. Due to the advantages of microfluidic techniques, a number of microfluidic flow cytometers with 3D hydrodynamic focusing have been developed in recent decades. However, the existing devices consist of multiple layers of microfluidic channels and tedious fluidic interconnections. As a result, these devices often require complicated fabrication and professional operation. Consequently, the development of a robust and reliable microfluidic flow cytometer for practical biological applications is desired. This paper develops a microfluidic device with a single channel layer and single sheath-flow inlet capable of achieving 3D hydrodynamic focusing for flow cytometry. The sheath-flow stream is introduced perpendicular to the microfluidic channel to encircle the sample flow. In this paper, the flow fields are simulated using a computational fluidic dynamic (CFD) software, and the results show that the 3D hydrodynamic focusing can be successfully formed in the designed microfluidic device under proper flow conditions. The developed device is further characterized experimentally. First, confocal microscopy is exploited to investigate the flow fields. The resultant Z-stack confocal images show the cross-sectional view of 3D hydrodynamic with flow conditions that agree with the simulated ones. Furthermore, the flow cytometric detections of fluorescence beads are performed using the developed device with various flow rate combinations. The measurement results demonstrate that the device can achieve great detection performances, which are comparable to the conventional flow cytometer. In addition, the enumeration of fluorescence-labelled cells is also performed to show its practicality for biological applications. Consequently, the microfluidic flow cytometer developed in this paper provides a practical platform that can be used for routine analysis in biological laboratories. Additionally, the 3D hydrodynamic focusing channel design can also be applied to various applications that can advance the lab on a chip research.
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An Evaluation of Dried Blood Spots and Oral Swabs As Alternative Specimens for the Diagnosis of Dengue and Screening for Past Dengue Virus Exposure
The American Journal of Tropical Medicine and Hygiene.
Jul, 2012 |
Pubmed ID: 22764309 Non-invasive specimens for dengue diagnosis may be preferable where venous blood is difficult to collect and/or process, such as community-based or remote settings or when sampling from young children. We evaluated the performance of oral swabs and dried blood spots (DBS), compared with plasma, in diagnosing acute dengue and screening for past dengue virus (DENV) exposure. DENV-specific immunoglobulin (Ig) M, IgG, and NS1 antigen were detected both in oral swabs and DBS from acute patients. Oral swabs were less sensitive (IgM: 68.7%, IgG: 91.9%, NS1: 64.7%), but retained good specificity (100%, 92.3%, 95.8%, respectively) compared with plasma. DBS displayed high sensitivity (IgM: 100%, IgG: 96%, NS1: 100%) and specificity (IgM: 75%, IgG: 93%). DENV RNA was amplified from DBS (sensitivity 95.6%) but not from oral swabs. DENV-IgG (indicative of past flavivirus exposure) were detected with moderate sensitivity (61.1%) but poor specificity (50%) in oral swabs from healthy volunteers. Dried blood spots allow sensitive and specific diagnosis of acute dengue by serological, molecular, and antigen detection methods. Oral swabs may be an adequate alternative where blood cannot be collected.
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In Vitro Suppression of Growth of Murine WEHI-3 Leukemia Cells and in Vivo Promotion of Phagocytosis in a Leukemia Mice Model by Indole-3-carbinol
Journal of Agricultural and Food Chemistry.
Aug, 2012 |
Pubmed ID: 22775144 Indole-3-carbinol (I3C), a potential anticancer substance, can be found in cruciferous (cabbage family) vegetables, mainly cauliflower and Chinese cabbage. However, the bioactivity of I3C on the apoptotic effects of murine leukemia WEHI-3 cells and promotion of immune responses in leukemia mice model are unclear. In this study, we investigated the effect of I3C on cell-cycle arrest and apoptosis in vitro and immunomodulation in vivo. I3C decreased the viable WEHI-3 cells and caused morphological changes in a concentration- and time-dependent manner. I3C also led to G0/G1 phase arrest, decreased the levels of cyclin A, cyclin D, and CDK2, and increased the level of p21(WAF1/CIP1). Flow cytometric analyses further proved that I3C promoted ROS and intracellular Ca(2+) production and decreased the levels of ΔΨ(m) in WEHI-3 cells. Cells after exposure to I3C for 24 h showed DNA fragmentation and chromatin condensation. Comet assay also indicated that I3C induced DNA damage in examined cells. I3C increased the levels of cytochrome c, FADD, GADD153, GRP78, and caspase-12 as well as induced activities of caspase-3, -8, and -9. Moreover, I3C attenuated NF-κB DNA binding activity in I3C-treated WEHI-3 cells as shown by EMSA and Western blotting analyses. In the in vivo study, we examined the effects of I3C on WEHI-3 leukemia mice. Results showed that I3C increased the level of T cells and decreased the level of macrophages. I3C also reduced the weights of liver and spleen, and it promoted phagocytosis by macrophages as compared to the nontreated leukemia mice group. On the basis of our results, I3C affects murine leukemia WEHI-3 cells both in vitro and in vivo.
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The Hypouricemic Effect of Balanophora Laxiflora Extracts and Derived Phytochemicals in Hyperuricemic Mice
Evidence-based Complementary and Alternative Medicine : ECAM.
2012 |
Pubmed ID: 22778779 The objective of this study is to evaluate the lowering of uric acid using Balanophora laxiflora extracts and derived phytochemicals on potassium-oxonate-(PO-) induced hyperuricemia in mice. The results revealed that ethyl acetate (EtOAc) fraction of B. laxiflora extracts exhibited strong xanthine-oxidase-(XOD-) inhibitory activity. In addition, among the 10 subfractions (EA1-10) derived from EtOAc fraction, subfraction 8 (EA8) exhibited the best XOD-inhibitory activity. Four specific phytochemicals, 1-O-(E)-caffeoyl-β-D-glucopyranose (1), 1-O-(E)-p-coumaroyl-β-D-glucopyranose (2), 1,3-di-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-β-D-glucopyranose (3), and 1-O-(E)-caffeoyl-4,6-(S)-hexahydroxydiphenoyl-β-D-glucopyranose (4), were further isolated and identified from this subfraction. Compounds 3 and 4 exhibited the strongest XOD-inhibitory activity compared with other compounds, and both hydrolyzable tannins were determined to be noncompetitive inhibitors according to the Lineweaver-Burk plot. On the other hand, the in vivo hypouricemic effect in hyperuricemic mice was consistent with XOD-inhibitory activity, indicating that B. laxiflora extracts and derived phytochemicals could be potential candidates as new hypouricemic agents.
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Oscillation in Cycle Length Induces Transient Discordant and Steady-state Concordant Alternans in the Heart
PloS One.
2012 |
Pubmed ID: 22792346 Alternans is a beat-to-beat alternation of the cardiac action potential duration (APD) or intracellular calcium (Ca(i)) transient. In cardiac tissue, alternans can be spatially concordant or discordant, of which the latter has been shown to increase dispersion of repolarization and promote a substrate for initiation of ventricular fibrillation. Alternans has been studied almost exclusively under constant cycle length pacing conditions. However, heart rate varies greatly on a beat-by-beat basis in normal and pathological conditions. The purpose of this study was to determine if applying a repetitive but non-constant pacing pattern, specifically cycle length oscillation (CLO), promotes or suppresses a proarrhythmic substrate. We performed computational simulations and optical mapping experiments to investigate the potential consequences of CLO. In a single cell computational model, CLO induced APD and Ca(i) alternans, which became "phase-matched" with the applied oscillation. As a consequence of the phase-matching, in one-dimensional cable simulations, neonatal rat ventricular myocyte monolayers, and isolated adult guinea pig hearts CLO could transiently induce spatial and electromechanical discordant alternans followed by a steady-state of concordance. Our results demonstrated that under certain conditions, CLO can initiate ventricular fibrillation in the isolated hearts. On the other hand, CLO can also exert an antiarrhythmic effect by converting an existing state of discordant alternans to concordant alternans.
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Mirtazapine Inhibits Tumor Growth Via Immune Response and Serotonergic System
PloS One.
2012 |
Pubmed ID: 22808019 To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug) and drug (mirtazapine), and four groups with tumors, i.e. never (no drug), always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment), concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment), and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment). The "psychiatric" conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interleukin-12 (sIL-12) and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after) as compared with that of never. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-α (TNF-α) expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [(123)I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.
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Clustered DNA Methylation Changes in Polycomb Target Genes in Early-stage Liver Cancer
Biochemical and Biophysical Research Communications.
Aug, 2012 |
Pubmed ID: 22842566 Polycomb-group proteins mark specific chromatin conformations in embryonic and somatic stem cells that are critical for maintenance of their "stemness". These proteins also mark altered chromatin modifications identified in various cancers. In normal differentiated cells or advanced cancerous cells, these polycomb-associated loci are frequently associated with increased DNA methylation. It has thus been hypothesized that changes in DNA methylation status within polycomb-associated loci may dictate cell fate and that abnormal methylation within these loci may be associated with tumor development. To assess this, we examined the methylation states of four polycomb target loci -Trip10, Casp8AP2, ENSA, and ZNF484 - in liver cancer. These four targets were selected because their methylation levels are increased during mesenchymal stem cell-to-liver differentiation. We found that these four loci were hypomethylated in most early-stage liver cancer specimens. For comparison, two non-polycomb tumor suppressor genes, HIC1 and RassF1A, were also examined. Whereas the methylation level of HIC1 did not differ significantly between normal and tumor samples, RassF1A was significantly hypermethylated in liver tumor samples. Unsupervised clustering analysis classified the methylation changes within polycomb and non-polycomb targets to be independent, indicating independent epigenetic evolution. Thus, pre-deposited polycomb marks within somatic stem cells may contribute to the determination of methylation changes during hepatic tumorigenesis.
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Integrated Electrofluidic Circuits: Pressure Sensing with Analog and Digital Operation Functionalities for Microfluidics
Lab on a Chip.
Oct, 2012 |
Pubmed ID: 22842773 Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.
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[Preventing Common Enteral Feeding Complications in Critically Ill Adult Patients]
Hu Li Za Zhi The Journal of Nursing.
Aug, 2012 |
Pubmed ID: 22851390 Nutritional support provides critically ill patients with energy and nutrients required to face the demands of their illness and stress. For those unable to ingest orally, enteral feeding rather than parenteral feeding is recommended, as the former better preserves gut integrity, reduces risk of infection, and costs less. Early enteral feeding in critically ill patients is also associated with decreased disease severity, reduced complications, and shortened length of stay. Risks associated with enteral feeding include aspiration, diarrhea, vomiting, hyponatremia, and hyperglycemia. This article reviews current knowledge on enteral feeding and addresses correct feeding tube placement, proper feeding sites, assessing and managing gastric residual volume, and preventing feeding tube occultation. We also review information related to identifying and controlling risk factors for enteral feeding complications such as aspiration, diarrhea, vomiting, hyponatremia, and hyperglycemia. Nurses can use this information to provide high quality care for enteral feeding patients and develop institutional protocols, guidelines, and standards of care for such patients in intensive care units.
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Optofluidic Detection for Cellular Phenotyping
Lab on a Chip.
Oct, 2012 |
Pubmed ID: 22854915 Quantitative analysis of the output of processes and molecular interactions within a single cell is highly critical to the advancement of accurate disease screening and personalized medicine. Optical detection is one of the most broadly adapted measurement methods in biological and clinical assays and serves cellular phenotyping. Recently, microfluidics has obtained increasing attention due to several advantages, such as small sample and reagent volumes, very high throughput, and accurate flow control in the spatial and temporal domains. Optofluidics, which is the attempt to integrate optics with microfluidics, shows great promise to enable on-chip phenotypic measurements with high precision, sensitivity, specificity, and simplicity. This paper reviews the most recent developments of optofluidic technologies for cellular phenotyping optical detection.
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Bufalin Increases Sensitivity to AKT/mTOR-induced Autophagic Cell Death in SK-HEP-1 Human Hepatocellular Carcinoma Cells
International Journal of Oncology.
Jul, 2012 |
Pubmed ID: 22858649 Bufalin is the major component of Chan-Su (a traditional Chinese medicine, TCM) extracts from the venom of Bufo bufo gargarizan. In the present study, we investigated the pharmacological mechanisms of cell cycle arrest and autophagic cell death induced by bufalin in SK-HEP-1 human hepatocellular carcinoma cells in vitro. Bufalin inhibited cell survival by MTT assay and increased cell death by trypan blue exclusion assay in a concentration-dependent manner. In addition, bufalin induced G2/M phase arrest by reducing CDK1 activity. Bufalin triggered DNA fragmentation and apoptotic cell death in SK-HEP-1 cells by DNA gel electrophoresis, TUNEL and caspase-3 activity assay, while bufalin induced autophagic cell death by double-membrane vacuoles (transmission electron microscopy, TEM), acidic vesicular organelles (acridine orange staining) and cleavage of microtubule-associated protein 1 light chain 3 (LC3). Protein expression levels of cyclin A and B, CDK1, phospho-CDK1 (Thr161), Cdc25c, phospho-Cdc25c (Ser198), phospho-AKT (Thr308), phospho-AKT (Ser473), phospho‑mTOR (Ser2481) were downregulated. In contrast, protein expression levels of the Chk1, Wee1, LC3-II, Beclin-1, Atg 5, Atg 7 and Atg 12 were upregulated in SK-HEP-1 cells after bufalin treatment. Inhibition of autophagy by 3-methyladenine (an inhibitor of class III phosphatidylinositol-3 kinase; 3-MA) or bafilomycin A1 (an inhibitor of the vacuolar proton pump of lysosomes and endosomes) reduced the effect of bufalin on cell viability and enhanced the effect of bufalin on apoptosis. In conclusion, bufalin triggered autophagic cell death and G2/M phase arrest through the AKT/mTOR signaling pathway in SK-HEP-1 cells. Our findings showed that bufalin may be potentially efficacious in the treatment of human hepatocellular carcinoma.
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C-myc in Kaposi's Sarcoma: Analyses by Fluorescent in Situ Hybridization and Immunohistochemistry
Journal of the European Academy of Dermatology and Venereology : JEADV.
Aug, 2012 |
Pubmed ID: 22882520 Background  The c-myc proto-oncogene plays a central role in the regulation of cellular transcription, differentiation, and apoptosis, and has been shown to be deregulated in many types of human cancer. Recent findings have demonstrated its amplification in select vascular neoplasms, such as secondary angiosarcomas, suggesting a role in angiogenesis as well. In vitro studies have shown that the c-Myc protein is an important regulatory molecule of spindle cell proliferation and migration in Kaposi's sarcoma (KS). Objectives  In light of these findings, our primary aim was to ascertain whether c-myc, by promoting proliferation and angiogenesis, is an essential co-factor in the aetiopathogenesis of KS. We also attempted to determine a correlation between immunohistochemical expression of the c-Myc protein and c-myc gene copy amplification using fluorescent in situ hybridization (FISH). Methods  Samples analyzed included archival tissue of KS (n = 24). PCR for detection of Kaposi's sarcoma-associated herpesvirus DNA was performed on all samples of KS. For FISH analyses, a dual-labelled technique was employed and probes for the c-myc gene and chromosome 8 were used. The monoclonal anti-c-myc antibody, 9E10, was used for immunohistochemical analyses. Results  While FISH analyses revealed no amplification of c-myc in any of the cases of KS, immunohistochemical analyses revealed positive staining for c-Myc in 13/24 cases (54%). Conclusions  Amplification of the c-myc gene was not witnessed in this preliminary study of 24 cases and thus cannot be correlated with the expression of the c-Myc protein.
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Getting Under—and Through—the Skin: Ecological Genomics of Chytridiomycosis Infection in Frogs
Molecular Ecology.
Jul, 2012 |
Pubmed ID: 22916344 Amphibian species around the world are currently becoming endangered or lost at a rate that outstrips other vertebrates—victims of a combination of habitat loss, climate change and susceptibility to emerging infectious disease (Stuart et al. 2004). One of the most devastating such diseases is caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), which infects hundreds of amphibian species on multiple continents. While Bd itself has been characterized for some time, we still know little about the mechanisms that make it so deadly. In this issue of Molecular Ecology, Rosenblum et al. describe a genomic approach to this question, reporting the results of a genome-wide analysis of the transcriptional response to Bd in the liver, skin and spleen of mountain yellow-legged frogs (Rana mucosa and R. sierrae: Fig. 1) (Rosenblum et al. 2012). Their results indicate that the skin is not only the first, but likely the most important, line of defence in these animals. Strikingly, they describe a surprisingly modest immune response to infection in Rana, a result that may help explain variable Bd susceptibility across populations and species.
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Serotonin (5-HT) Activation of Immortalized Hypothalamic Neuronal Cells Through the 5-HT1B Serotonin Receptor
Endocrinology.
Oct, 2012 |
Pubmed ID: 22919062 Serotonin [or 5-hydroxytryptamine or (5-HT)] has been implicated as a key modulator in energy homeostasis and a primary focus in the treatment of obesity. There is growing evidence that 5-HT, acting through the 5-HT 1B receptor (5-HT(1B)R) in the paraventricular nucleus of the hypothalamus (PVN), is important to this regulation. However, there is some contention as to whether 5-HT(1B)R action occurs directly on PVN neurons or indirectly via inhibitory inputs into the PVN. To address these questions, we used a novel clonal, hypothalamic neuronal cell model, adult mouse hypothalamic-2/30 (mHypoA-2/30), expressing a PVN-specific marker, single-minded homolog 1, as well as a complement of PVN neuropeptides, including TRH, vasopressin, ghrelin, nucleobindin-2, and galanin. Adult mouse hypothalamic-2/30 neurons were also found to express the 5-HT(1B)R and 5-HT 6 receptor, but not 2C, all previously linked to feeding regulation. Direct serotonergic stimulation (100 nm to 10 μm) of these neurons resulted in dose-dependent cFos activation. 5-HT (10 μm) suppressed forskolin-induced cAMP levels and induced a rise in intracellular Ca(2+) through ER Ca(2+) release, effects that were mimicked by the 5-HT(1B)R agonists, CGS12066B and CP93129, and that were attenuated in the presence of the 5-HT(1B)R-specific inhibitors, GR55562 and isamoltane hemifumarate. Modest transcriptional changes in ghrelin and nucleobindin-2 were also observed in response to 100 nm and 10 μm 5-HT, respectively. These findings support the model wherein 5-HT action through the 1B receptor subtype occurs directly on PVN neurons, leading to potential modification of neuronal transcriptional and secretory machinery.
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Electrophysiological and Contractile Function of Cardiomyocytes Derived from Human Embryonic Stem Cells
Progress in Biophysics and Molecular Biology.
Oct-Nov, 2012 |
Pubmed ID: 22958937 Human embryonic stem cells have emerged as the prototypical source from which cardiomyocytes can be derived for use in drug discovery and cell therapy. However, such applications require that these cardiomyocytes (hESC-CMs) faithfully recapitulate the physiology of adult cells, especially in relation to their electrophysiological and contractile function. We review what is known about the electrophysiology of hESC-CMs in terms of beating rate, action potential characteristics, ionic currents, and cellular coupling as well as their contractility in terms of calcium cycling and contraction. We also discuss the heterogeneity in cellular phenotypes that arises from variability in cardiac differentiation, maturation, and culture conditions, and summarize present strategies that have been implemented to reduce this heterogeneity. Finally, we present original electrophysiological data from optical maps of hESC-CM clusters.
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Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells As Models for Normal and Diseased Cardiac Electrophysiology and Contractility
Progress in Biophysics and Molecular Biology.
Oct-Nov, 2012 |
Pubmed ID: 22971665 Since the first description of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), these cells have garnered tremendous interest for their potential use in patient-specific analysis and therapy. Additionally, hiPSC-CMs can be derived from donor cells from patients with specific cardiac disorders, enabling in vitro human disease models for mechanistic study and therapeutic drug assessment. However, a full understanding of their electrophysiological and contractile function is necessary before this potential can be realized. Here, we review this emerging field from a functional perspective, with particular emphasis on beating rate, action potential, ionic currents, multicellular conduction, calcium handling and contraction. We further review extant hiPSC-CM disease models that recapitulate genetic myocardial disease.
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'Many People Know the Law, but Also Many People Violate It': Discrimination Experienced by People Living with HIV/AIDS in Vietnam - Results of a National Study
Global Public Health.
Sep, 2012 |
Pubmed ID: 22974225 Abstract In Vietnam, discrimination against people living with HIV/AIDS (PLHIV) is defined within and prohibited by the 2007 national HIV/AIDS law. Despite the law, PLHIV face discrimination in health care, employment, education and other spheres. This study presents the first national estimates of the levels and types of discrimination that are defined in Vietnamese law and experienced by PLHIV in Vietnam. A nationally representative sample of 1200 PLHIV was surveyed, and 129 PLHIV participated in focus group discussions (FGDs). In the last 12 months, nearly half of the survey population experienced at least one form of discrimination and many experienced up to six different types of discrimination. The most common forms of discrimination included disclosure of HIV status without consent; denial of access to education for children; loss of employment; advice, primarily from health care providers, to abstain from sex; and physical and emotional harm. In logistic regression analysis, the experience of discrimination differed by gender, region of residence and membership status in a PLHIV support group. The logistic regression and FGD results indicate that disclosure of HIV status without consent was associated with experiencing other forms of discrimination. Key programme and policy recommendations are discussed.
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Lymphatic Endothelial Cells Induce Tolerance Via PD-L1 and Lack of Costimulation Leading to High-level PD-1 Expression on CD8 T Cells
Blood.
Dec, 2012 |
Pubmed ID: 22993390 Lymphatic endothelial cells (LECs) induce peripheral tolerance by direct presentation to CD8 T cells (T(CD8)). We demonstrate that LECs mediate deletion only via programmed cell death-1 (PD-1) ligand 1, despite expressing ligands for the CD160, B- and T-lymphocyte attenuator, and lymphocyte activation gene-3 inhibitory pathways. LECs induce activation and proliferation of T(CD8), but lack of costimulation through 4-1BB leads to rapid high-level expression of PD-1, which in turn inhibits up-regulation of the high-affinity IL-2 receptor that is necessary for T(CD8) survival. Rescue of tyrosinase-specific T(CD8) by interference with PD-1 or provision of costimulation results in autoimmune vitiligo, demonstrating that LECs are significant, albeit suboptimal, antigen-presenting cells. Because LECs express numerous peripheral tissue antigens, lack of costimulation coupled to rapid high-level up-regulation of inhibitory receptors may be generally important in systemic peripheral tolerance.
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A (13)C and (1)H NMR Spectroscopic Investigation of the Structure of the Iminium Ion with a Dipolar Form in Metal Complexes of 2-N-substituted N-confused Porphyrins
Dalton Transactions (Cambridge, England : 2003).
Nov, 2012 |
Pubmed ID: 23010770 The crystal structures of chloro(2-aza-2-ethoxycarbonylmethyl-5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N'') zinc(ii) [Zn(2-NCH(2)COOC(2)H(5)NCTPP)Cl; ], (2-aza-2-ethoxycarbonylmethyl-5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N'') palladium(ii) [Pd(2-NCH(2)COOC(2)H(5)NCTPP); ], bromo(2-aza-2-ethoxycarbonylmethyl-5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N'') manganese(iii) [Mn(2-NCH(2)COOC(2)H(5)NCTPP)Br; ], [2-aza-(3'-phenoxypropyl)-5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N''] nickel(ii) [Ni(2-NCH(2)CH(2)CH(2)OC(6)H(5)NCTPP); ] and chloro(2-aza-2-methoxycarbonylmethyl-5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N'') zinc(ii) [Zn(2-NCH(2)COOCH(3)NCTPP)Cl; ] have been established. The g value of 9.54, which was measured from the parallel polarization of the X-band EPR spectra in CHCl(3) at 4 K, is consistent with the high spin mononuclear manganese(iii) centre (S = 2) in . The magnitude of the axial (D) zero-field splitting (ZFS) for the mononuclear Mn(iii) centre in was determined approximately to be 1.63 cm(-1) by paramagnetic susceptibility measurements. The NMR spectroscopic investigation of the iminium ion with a dipolar canonical contribution to the metal complexes , Pd(2-NCH(2)C(6)H(5)NCTPP) () and Ni(2-NCH(2)C(6)H(5)NCTPP) () in CDCl(3) is reported. A resonance between the dipolar canonical form and covalent canonical form exists for complexes , and in CDCl(3). To develop the correlations between δ(13)C [C(3)], δ(1)H [H(3)] and the canonical form in , and , this work thoroughly examines the (13)C and (1)H NMR of N(+)[double bond, length as m-dash]CH(Ar) fragment on seven metal complexes of 2-N substituted N-confused porphyrin. According to these results, the (13)C [C(3)] and (1)H [H(3)] chemical shifts of the N(+)[double bond, length as m-dash]CH(Ar) fragment at 20 °C in CDCl(3) are separately located at 152.6 ± 0.5 and 8.30 ± 0.15 ppm respectively for the iminium ion. This exists as a dipolar canonical form for complexes , and , and the N-CH(Ar) group appears at 121.1 ± 0.1 ppm and 6.35 ± 0.01 ppm, which is in a covalent canonical form contribution to complexes and . X-Ray diffraction data indicate that N(2)-C(3) = 1.315 ± 0.011 Å for the dipolar contribution of , , while N(2)-C(3) = 1.331 ± 0.008 Å for the covalent contribution of and .
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Increased Placental Nutrient Transporter Expression at Midgestation After Maternal Growth Hormone Treatment in Pigs: a Placental Mechanism for Increased Fetal Growth
Biology of Reproduction.
Nov, 2012 |
Pubmed ID: 23018188 Growth hormone (GH) is important in maternal adaptation to pregnancy, and maternal circulating GH concentrations are reduced in human growth-restricted pregnancies. In the pig, maternal GH treatment throughout early to mid pregnancy increases fetal growth, despite constraining effects of adolescent and primiparous pregnancy, high litter size, and restricted maternal nutrition. Because GH cannot cross the placenta and does not increase placental weight, we hypothesized that its effects on fetal growth might be via improved placental structure or function. We therefore investigated effects of maternal GH treatment in pigs on structural correlates of placental function and placental expression of nutrient transporters important to fetal growth. Multiparous (sows) and primiparous pregnant pigs (gilts) were treated with GH (~15 μg kg(-1) day(-1)) or vehicle from Days 25-50 of gestation (n = 7-8 per group, term ~115 days). Placentas were collected at Day 50 of gestation, and we measured structural correlates of function and expression of SLC2A1 (previously known as GLUT1) and SLC38A2 (previously known as SNAT2) nutrient transporters. Maternal GH treatment did not alter placental size or structure, increased protein expression of SLC2A1 in trophoblast (+35%; P = 0.037) and on its basal membrane (+44%; P = 0.011), and increased SLC38A2 protein expression in the basal (+44%; P = 0.001) but not the apical cytoplasm of trophoblast. Our findings suggest that maternal GH treatment increases fetal growth, in part, by enhancing placental nutrient transporter protein expression and hence fetal nutrient supply as well as trophoblast proliferation and differentiation and may have the potential to ameliorate intrauterine growth restriction.
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Blue Light Acts As a Double-edged Sword in Regulating Sexual Development of Hypocrea Jecorina (Trichoderma Reesei)
PloS One.
2012 |
Pubmed ID: 23028710 The industrially important cellulolytic filamentous fungus Trichoderma reesei is the anamorph of the pantropical ascomycete Hypocrea jecorina. H. jecorina CBS999.97 strain undergoes a heterothallic reproductive cycle, and the mating yields fertilized perithecia imbedded in stromata. Asci in the perithecia contain 16 linearly arranged ascospores. Here, we investigated H. jecorina sexual development under different light regimes, and found that visible light was dispensable for sexual development (stroma formation and ascospore discharge). By contrast, constant illumination inhibited stroma formation, and an interruption of the darkness facilitated timely stroma formation in a 12 h/12 h light-dark photoperiod. The results of genetic analyses further revealed that H. jecorina blue-light photoreceptors (BLR1, BLR2) and the photoadaptation protein ENV1 were not essential for sexual development in general. BLR1, BLR2 and ENV1 are orthologues of the conserved Neurospora crassa WC-1, WC-2 and VVD, respectively. Moreover, BLR1 and BLR2 mediate both positive and negative light-dependent regulation on sexual development, whereas ENV1 is required for dampening the light-dependent inhibitory effect in response to changes in illumination. Comparative genome-wide microarray analysis demonstrated an overview of light-dependent gene expression versus sexual potency in CBS999.97 (MAT1-2) haploid cells. Constant illumination promotes abundant asexual conidiation and high levels of hpp1 transcripts. hpp1 encodes a h (hybrid)-type propheromone that exhibits features of both yeast a and a pheromone precursors. Deletion of hpp1 could rescue stroma formation but not ascospore generation under constant illumination. We inferred that the HPP1-dependent pheromone signaling system might directly prevent stroma formation or simply disallow the haploid cells to acquire sexual potency due to abundant asexual conidiation upon constant illumination.
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Temporal Horizons in Pain Management: Understanding the Perspectives of Physicians, Physical Therapists, and Their Middle-Aged and Older Adult Patients
The Gerontologist.
Oct, 2012 |
Pubmed ID: 23103522 PURPOSE: The management of chronic noncancer pain (CNCP) involves trade-offs between immediate and delayed consequences of various treatments. Temporal trade-offs may be particularly salient for older adults because of age-related differences in prognosis and perceptions of future time. This study examined how perceptions of time influence the management of CNCP among patients and providers with particular emphasis on age differences. DESIGN AND METHODS: Focus groups were conducted with 28 CNCP patients (5 groups), 21 physicians (4 groups), and 23 physical therapists (3 groups). Audiotapes were transcribed and analyzed using standard qualitative methods. RESULTS: Analyses identified multiple aspects of time perceptions that are relevant to the management of CNCP: the long-term prognosis, the time horizon used for concrete treatment planning, and concerns about future side effects. Although there was some overlap, these aspects showed divergent patterns across age groups and between patients and providers. Patients and providers agreed that pain is more stable and chronic in older adults. Time horizons in treatment planning differed between patients who were present-focused and providers who were focused on longer term effects, but treatment horizons did not differ by patient age. Finally, although providers were more concerned about future side effects in older people, patients' concerns did not differ by age. IMPLICATIONS: Time horizons have practical implications for the quality of the patient-provider relationship and self-management of CNCP. A better understanding of the underlying mechanisms could inform interventions to reduce age disparities in pain care.
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Accurate Potential Energy Curves for HeH+ Isotopologues
The Journal of Chemical Physics.
Oct, 2012 |
Pubmed ID: 23126708 New accurate ground-state potential energy curves (PEC) for the (4)HeH(+), (4)HeD(+), (3)HeH(+), and (3)HeD(+) isotopologues are calculated with 600 explicitly correlated Gaussian (ECG) functions with shifted centers in the range between R = 0.35 a(0) and 145 a(0). The calculations include the adiabatic corrections (AC). The absolute accuracy of all Born-Oppenheimer (BO) PEC points is better than 0.0018 cm(-1) and it is better than 0.0005 cm(-1) for the ACs. With respect to the very recent BO PEC calculations performed by Pachucki with 20 000 generalized Heitler-London explicitly correlated functions [K. Pachucki, Phys. Rev. A 85, 042511 (2012)], the present energy calculated at R = 1.46 a(0) (a point near the BO equilibrium distance) lies above by only 0.0012 cm(-1). Using Pachucki's BO energy at the equilibrium distance of R = 1.463 283 a(0), and the adiabatic corrections calculated in this work for the (4)HeH(+), (4)HeD(+), (3)HeH(+), and (3)HeD(+) isotopologues, the following values are obtained for their PEC depths: 16 448.99893 cm(-1), 16 456.86246 cm(-1), 16 451.50635 cm(-1), and 16 459.36988 cm(-1), respectively. We also calculate the rovibrational (rovib) frequencies for the four isotopologues using the BO PEC of Pachucki augmented with the present ACs. The improvements over the BO+AC PEC of Bishop and Cheung (BC) [J. Mol. Spectrosc. 75, 462 (1979)] are 1.522 cm(-1) at R = 4.5 a(0) and 0.322 cm(-1) at R = ∞. To partially account for the nonadiabatic effects in the rovib calculations an effective reduced-mass approach is used. With that, the present (4)HeH(+) rovibrational transitions are considerably improved over the BC transitions as compared with the experimental values. Now the rovibrational transitions near the dissociation limit are as well reproduced by the present calculations as the lower transitions. For example, for the (4)HeD(+) transitions corresponding to the ν = 13-9 hot bands the results are off from the experimental values by less than 0.023 cm(-1). This confirms high accuracy of the present PECs at larger internuclear separations.
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Efficient Separation and Sensitive Detection of Listeria Monocytogenes Using an Impedance Immunosensor Based on Magnetic Nanoparticles, a Microfluidic Chip, and an Interdigitated Microelectrode
Journal of Food Protection.
Nov, 2012 |
Pubmed ID: 23127703 Listeria monocytogenes continues to be a major foodborne pathogen that causes food poisoning, and sometimes death, among immunosuppressed people and abortion among pregnant women. In this study, magnetic nanoparticles with a diameter of 30 nm were functionalized with anti-L. monocytogenes antibodies via biotin-streptavidin bonds to become immunomagnetic nanoparticles (IMNPs) to capture L. monocytogenes in a sample during a 2-h immunoreaction. A magnetic separator was used to collect and hold the IMNPs-L. monocytogenes complex while the supernatants were removed. After the washing step, the nanoparticle-L. monocytogenes complex was separated from the sample and injected into a microfluidic chip. The impedance change caused by L. monocytogenes was measured by an impedance analyzer through the interdigitated microelectrode in the microfluidic chip. For L. monocytogenes in phosphate-buffered saline solution, up to 75% of the cells in the sample could be separated, and as few as three to five cells in the microfluidic chip could be detected, which is equivalent to 10(3) CFU/ml of cells in the original sample. The detection of L. monocytogenes was not interfered with by other major foodborne bacteria, including E. coli O157:H7, E. coli K-12, L. innocua, Salmonella Typhimurium, and Staphylococcus aureus. A linear correlation (R(2) = 0.86) was found between the impedance change and the number of L. monocytogenes in a range of 10(3) to 10(7) CFU/ml. Equivalent circuit analysis indicated that the impedance change was mainly due to the decrease in medium resistance when the IMNPs-L. monocytogenes complexes existed in mannitol solution. Finally, the immunosensor was evaluated with food sample tests; the results showed that, without preenrichment and labeling, 10(4) and 10(5) CFU/ml L. monocytogenes in lettuce, milk, and ground beef samples could be detected in 3 h.
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PPAR-alpha is a Therapeutic Target for Chronic Lymphocytic Leukemia
Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K.
Nov, 2012 |
Pubmed ID: 23160450 Chronic lymphocytic leukemia (CLL) cells with aggressive clinical properties express lipoprotein lipase (LPL), which generates activating ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)α and allows fatty acids to be used as fuel. However, the role of PPARα in CLL is unclear. PPARα was found to be expressed by circulating CLL cells and highly associated with advanced stage disease. Consistent with this observation, palmitate oxidation rates in circulating CLL cells were similar to more conventional fat-burning cells such as muscle. Transgenic expression of PPARα in CD5(+) Daudi cells increased both their expression of immunosuppressive factors (that is, interleukin (IL)10 and phospho-STAT3) and resistance to metabolic and cytotoxic stressors. In contrast, marked downregulation of PPARα expression accompanied immunogenic death of proliferating CLL cells. The PPARα antagonist MK886 killed circulating CLL cells directly, caused proliferating CLL cells to enter an immunogenic death pathway and cleared CLL xenografts from immunodeficient mice. These results suggest that PPARα is a biological mediator of CLL and MK886 is a clinically relevant agent with activity against CLL.Leukemia advance online publication, 7 December 2012; doi:10.1038/leu.2012.329.
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Anti-citrullinated Protein Antibodies Activated ERK1/2 and JNK Mitogen-activated Protein Kinases Via Binding to Surface-expressed Citrullinated GRP78 on Mononuclear Cells
Journal of Clinical Immunology.
Nov, 2012 |
Pubmed ID: 23188524 In a previous study, we found that anti-citrullinated protein antibodies (ACPAs) enhance nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α production by normal human peripheral blood mononuclear cells (PBMCs) and U937 cells via binding to surface-expressed citrullinated glucose-regulated protein 78 (cit-GRP78). However, the downstream signaling pathways remain unclear after binding. In the present study, we firstly measured the effects of different kinase inhibitors on ACPA-mediated TNF-α production from normal PBMCs and monocytes. Then, the native and phosphorylated mitogen-activated protein kinases (MAPKs) were detected in ACPA-activated U937 cells by Western blotting. We also explored the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in activating IκB kinase alpha (IKK-α) in ACPA-stimulated U937 cells. Finally, we measured the amount of cit-GRP78 from PBMC membrane extracts in RA patients and controls. We found that MAPK and Akt inhibitors, but not PI3K inhibitor, remarkably suppressed ACPA-mediated TNF-α production. Interestingly, ACPAs selectively activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK), but not p38 MAPK, in U937 cells. This activation was suppressed by cit-GRP78, but not GRP78. The JNK activation further enhanced the phosphorylation of Akt and IKK-α. The expression of cit-GRP78 on cell membrane was higher in RA than normal PBMCs. Taken together; these results suggest that through binding to surface, over-expressed cit-GRP78 on RA PBMCs, ACPAs selectively activate ERK1/2 and JNK signaling pathways to enhance IKK-α phosphorylation, which leads to the activation of NF-κB and the production of TNF-α .
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Radiotherapy Concurrently with Weekly Cisplatin, Followed by Adjuvant Chemotherapy, for N2-3 Nasopharyngeal Cancer: a Multicenter Trial of the Forum for Nuclear Cooperation in Asia
Journal of Radiation Research.
Nov, 2012 |
Pubmed ID: 23192700 The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2-3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1-4 N2-3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30Â mg/m (2)), followed by adjuvant chemotherapy, consisting of cisplatin (80Â mg/m(2) on Day 1) and fluorouracil (800Â mg/m(2) on Days 1-5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3-4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities.
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Establishment of a Bioluminescence-based Bioassay for the Detection of Dioxin-like Compounds
Toxicology Mechanisms and Methods.
Nov, 2012 |
Pubmed ID: 23193992 Abstract Dioxin and dioxin-like compounds are among the most prevalent and toxic environmental pollutants. At present, analytical chemical techniques are considered the gold standard for detection of dioxins. Here, we describe a highly sensitive and cost-effective alternative, based on bioluminescence and bioluminescence resonance energy transfer (BRET). Upon binding to dioxin, Aryl hydrocarbon receptor (AHR) dissociates from HSP90 and subsequently translocates to the nucleus, where it interacts with AHR nuclear translocator (ARNT). We generated cell lines that stably co-express a fusion protein of AHR and Renilla luciferase (AHR-RL) and either HSP90 or ARNT tagged with yellow fluorescent protein (HSP90-YFP or ARNT-YFP). The fluorescent signals of YFP are activated by the emission of RL while the interactions between AHR and HSP90 (or ARNT) were monitored. Application of 3-methylcholanthrene (3MC), the AHR agonist, enhances BRET signals in cells co-expressing AHR-RL, AIP-HIS, P23-HIS and ARNT-YFP (AAPA cells), while suppressing BRET signals in cells co-expressing AHR-RL, AIP-HIS, P23-HIS and HSP90-YFP (AAPH cells). In addition, dioxin treatment reduced Renilla luminescence in AAPH cells in a concentration-dependent manner, due to degradation of AHR. Intriguingly, the detection limit for dioxin in our AHR degradation assay was as low as 10(-17) M. This work highlights the potential of AHR-RL degradation assays to detect dioxin-like pollutants.
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Diterpenoids from the Soft Coral Sinularia Maxima and Their Inhibitory Effects on Lipopolysaccharide-stimulated Production of Pro-inflammatory Cytokines in Bone Marrow-derived Dendritic Cells
Chemical & Pharmaceutical Bulletin.
2012 |
Pubmed ID: 23207638 Nine new diterpenoids, termed sinumaximols A-I (1-3, 5-9, 12), together with three known compounds (4, 10, 11), were isolated from the methanol extract of the soft coral Sinularia maxima. Their structures were elucidated on the basis of extensive spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The isolated compounds were evaluated for their inhibitory effects on the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Among them, compounds 2, 3, and 11 were potent inhibitors of LPS-stimulated interleukin-12 (IL-12) p40 with half-maximal inhibitory concentration (IC(50)) values ranging from 4.35±0.12 to 18.04±0.21 µM. Compounds 2, 3, and 11 showed moderate inhibitory activity on IL-6 production with IC(50) values ranging from 17.72±0.31 to 59.77±2.34 µM.
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The Utilization of a Commercial Soil Nucleic Acid Extraction Kit and PCR for the Detection of Clostridium Tetanus and Clostridium Chauvoei on Farms After Flooding in Taiwan
The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science.
Dec, 2012 |
Pubmed ID: 23208321 Clostridial diseases are zoonoses and are classified as soil-borne diseases. Clostridium chauvoei and Clostridium tetani cause blackleg disease and tetanus, respectively. Since bacteria and spores are re-distributed by floods and then, subsequently, contaminate soils, pastures, and water; the case numbers associated with clostridial diseases usually increase after floods. Because Taiwan is often affected by flood damage during the typhoon season, possible threats from these diseases are present. Thus, this study's aim is to apply a combination of a commercial nucleic acid extraction kit and PCR to assess the prevalence of Clostridia spp. in soil and to compare the positivity rates for farms before and after floods. The minimum amounts of Clostridium tetanus and Clostridium chauvoei that could be extracted from soils and detected by PCR were 10 and 50 colony forming units (cfu), respectively. In total, 76 samples were collected from the central and southern regions of Taiwan, which are the areas that are most frequently damaged by typhoons. Noteworthy, the positive rates for Clostridium tetanus and Clostridium chauvoei in Pingtung county after the severe floods caused by a typhoon increased significantly from 13.73 and 7.84% to 53.85 and 50.00%, respectively. This study for the first time provides the evidence from surveillance data that there are changes in the environmental distribution of Clostridium spp. after floods. This study indicates that screening for soil-related zoonotic pathogens is a potential strategy that may help to control these diseases.
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Epicardial Ablation of Ventricular Tachycardia: An Institutional Experience of Safety and Efficacy
Heart Rhythm : the Official Journal of the Heart Rhythm Society.
Dec, 2012 |
Pubmed ID: 23246598 BACKGROUND: Epicardial ablation has been shown to be a useful adjunct for treatment of ventricular tachycardia (VT). OBJECTIVE: To report the trends, safety, and efficacy of epicardial mapping and ablation at a single center over an 8-year period. METHODS: Patients referred for VT ablation (June 2004 to July 2011) were divided into 3 groups: ischemic cardiomyopathy (ICM), nonischemic cardiomyopathy (NICM), and idiopathic ventricular arrhythmias (VA). Patients with scar-mediated VT who underwent combined epicardial and endocardial (epi-endo) mapping and ablation were compared with those who underwent endocardial-only (endo-only) ablation with regard to patient characteristics, acute procedural success, 6- and 12-month clinical outcomes. RESULTS: Among 144 patients referred for VT ablation, 95 patients underwent 109 epicardial procedures (94% access rate). Major complications were seen in 8 patients (8.8%) with pericardial bleeding (>80 cm(3)) in 6 cases (6.7%), although no tamponade, surgical intervention, or procedural mortality was seen. Patients with ICM who underwent a combined epi-endo ablation had improved freedom from VT compared with those who underwent endo-only ablation at 12 months (85% vs 56%; P = .03). In patients with NICM, no differences were seen between those who underwent epi-endo ablation and those who underwent endo-only ablation at 12 months (36% vs 33%; P = 1.0). In idiopathic VA, only 2 of 17 patients were successfully ablated from the epicardium. CONCLUSIONS: In this large tertiary single-center experience, complication rates are acceptably low and improved clinical outcomes were associated with epi-endo ablation in patients with ICM. Patients with NICM represent a growing referred population, although clinical recurrence remains high despite epicardial ablation. Epicardial ablation has a low yield in idiopathic VA.
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A Theoretical Model of Efficacy Beliefs, Functional Status and Quality of Life for Older People During Rehabilitation: Testing Causal Relationships
Journal of Advanced Nursing.
Dec, 2012 |
Pubmed ID: 23278105 AIMS: Structural equation modelling tested hypothesized causal relationships between age, gender, pain, depression, self-efficacy, outcome expectations, functional status and quality of life in older Australians postorthopaedics surgery across three stages of their rehabilitation. BACKGROUND: Self-efficacy is important in forming personal beliefs about capabilities to perform functional activities, which is believed to maintain individual's quality of life. Research examining how efficacy beliefs influence functional status in older people following orthopaedic events is limited. DESIGN: A descriptive, longitudinal method was used for this study. METHODS: A convenience sample of 101 older people with orthopaedic surgery to lower extremities was recruited from private rehabilitation units in Brisbane, Australia. Data were collected from September 2008-November 2009. Standardized questionnaires were used to measure efficacy beliefs, functional status, and quality of life. RESULTS: Structural equation modelling revealed that depression, efficacy beliefs, age, and gender significantly influenced quality of life, as self-efficacy and gender have a direct relationship on functional status. Across three stages in the model, outcome expectation at stage 2 was the most significant predictor of functional recovery after discharge. Older men with higher quality of life at admission was positively related to self-efficacy and negatively associated with depression at stage 2: quality of life influenced outcome expectations and pain positively at stage 3. CONCLUSION: Rehabilitation programmes play a significant role in assisting older people in resuming functional activities and quality of life following orthopaedic surgery. Enhancing self-efficacy may facilitate older people's participation and adher-ence to rehabilitation programmes during hospitalization and following discharge.
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Self-Management Intervention to Improve Self-Care and Quality of Life in Heart Failure Patients
Congestive Heart Failure (Greenwich, Conn.).
Dec, 2012 |
Pubmed ID: 23279120 Self-management intervention is a good method to improve self-care ability, as such, to promote quality of life. However, the research focused on self-management intervention in heart failure patients in Taiwan is very limited. Therefore, the purposes of this study were to test the effectiveness of self-management intervention in patients with heart failure in Taiwan and examine the relationship between self-care ability and quality of life. A quasi-experimental design was used in this study with convenience sampling. Of the 82 subjects participating in this study, 40 of them chose to join the experimental (self-management intervention plus usual care) and 42 of them chose to join control (usual care) group. Three questionnaires were used to collect the data, which were the demographic questionnaire, the self-care questionnaire (Self-Care of HF Index V 6), and the quality of life questionnaire (Minnesota Living with Heart Failure Questionnaire). To examine the effectiveness of the intervention, self-care ability and quality of life were measured, using a pretest, 1- and 2-month follow-up assessment. Generalized estimation equations (GEE) were used to compare changes over time among groups for outcomes to ensure the effectiveness of the intervention. This study confirmed the effectiveness of the self-management intervention. The clinical provider should increase the awareness of the importance of self-management skills and self-care ability especially for heart failure patients. The designated disease-specific self-management patient book and individualize intervention should be dispensing and implementing.
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Treponema Pallidum Infection in the Wild Baboons of East Africa: Distribution and Genetic Characterization of the Strains Responsible
PloS One.
2012 |
Pubmed ID: 23284649 It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum), yaws (subsp. pertenue), and bejel (subsp. endemicum) in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains.
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Identification of Orch3, a Locus Controlling Dominant Resistance to Autoimmune Orchitis, As Kinesin Family Member 1C
PLoS Genetics.
Dec, 2012 |
Pubmed ID: 23300462 Experimental autoimmune orchitis (EAO), the principal model of non-infectious testicular inflammatory disease, can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants. As previously established, the genome of DBA/2J mice encodes genes that are capable of conferring dominant resistance to EAO, while the genome of BALB/cByJ mice does not and they are therefore susceptible to EAO. In a genome scan, we previously identified Orch3 as the major quantitative trait locus controlling dominant resistance to EAO and mapped it to chromosome 11. Here, by utilizing a forward genetic approach, we identified kinesin family member 1C (Kif1c) as a positional candidate for Orch3 and, using a transgenic approach, demonstrated that Kif1c is Orch3. Mechanistically, we showed that the resistant Kif1c(D2) allele leads to a reduced antigen-specific T cell proliferative response as a consequence of decreased MHC class II expression by antigen presenting cells, and that the L(578) → P(578) and S(1027) → P(1027) polymorphisms distinguishing the BALB/cByJ and DBA/2J alleles, respectively, can play a role in transcriptional regulation. These findings may provide mechanistic insight into how polymorphism in other kinesins such as KIF21B and KIF5A influence susceptibility and resistance to human autoimmune diseases.
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Dietary Crocin Inhibits Colitis and Colitis-Associated Colorectal Carcinogenesis in Male ICR Mice
Evidence-based Complementary and Alternative Medicine : ECAM.
2012 |
Pubmed ID: 23326291 A natural carotenoid crocin is contained in saffron and gardenia flowers (crocuses and gardenias) and is used as a food colorant. This study reports the potential inhibitory effects of crocin against inflammation-associated mouse colon carcinogenesis and chemically induced colitis in male ICR mice. In the first experiment, dietary crocin significantly inhibited the development of colonic adenocarcinomas induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in mice by week 18. Crocin feeding also suppressed the proliferation and immunohistochemical expression of nuclear factor- (NF-) κB but increased the NF-E2-related factor 2 (Nrf2) expression, in adenocarcinoma cells. In the second experiment, dietary feeding with crocin for 4 weeks was able to inhibit DSS-induced colitis and decrease the mRNA expression of tumor necrosis factor α, interleukin- (IL-) 1β, IL-6, interferon γ, NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the colorectal mucosa and increased the Nrf2 mRNA expression. Our results suggest that dietary crocin suppresses chemically induced colitis and colitis-related colon carcinogenesis in mice, at least partly by inhibiting inflammation and the mRNA expression of certain proinflammatory cytokines and inducible inflammatory enzymes. Therefore, crocin is a candidate for the prevention of colitis and inflammation-associated colon carcinogenesis.
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Exploring the Structural Requirements of Collagen-binding Peptides
Biopolymers.
Nov, 2012 |
Pubmed ID: 23436394 Collagen synthesis and tissue remodeling are involved in many diseases; therefore collagen specific binding agents have been developed to study collagen changes in various tissues. Based on a recently reported collagen binding peptide, which contains unnatural Biphenylalanine (Bip) amino acid residue, constructs with various structure variations were synthesized to explore the contributions of unnatural Bip residue, conformational restrain, and amino acid sequence in collagen recognition. Their binding efficiency to collagens was evaluated in vitro using pure collagens. The results indicate that the C-terminal unnatural Bip residue, rather than the peptide sequence or conformational restrain, dominated the collagen I binding. Subsequent tissue binding study showed that the selected peptide didn't offer preferential selectivity over collagen I in tissue, suggesting that a simple in vitro binding assay cannot adequately model the complex biological environment. © 2012 Wiley Periodicals, Inc. Biopolymers, 2012.
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Inhibition of TNF-α-mediated NF-κB Transcriptional Activity in HepG2 Cells by Dammarane-type Saponins from Panax Ginseng Leaves
Journal of Ginseng Research.
Apr, 2012 |
Pubmed ID: 23717114 Panax ginseng (PG) is a globally utilized medicinal herb. The medicinal effects of PG are primarily attributable to ginsenosides located in the root and leaf. The leaves of PG are known to be rich in various bioactive ginsenosides, and the therapeutic effects of ginseng extract and ginsenosides have been associated with immunomodulatory and anti-inflammatory activities. We examined the effect of PG leaf extract and the isolated ginsenosides, on nuclear factor (NF)-κB transcriptional activity and target gene expression by applying a luciferase assay and reverse transcription polymerase chain reaction in tumor necrosis factor (TNF)-α-treated hepatocarcinoma HepG2 cells. Air-dried PG leaf extract inhibited TNF-α-induced NF-κB transcription activity and NF-κB-dependent cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) gene expression more efficiently than the steamed extract. Of the 10 ginsenosides isolated from PG leaves, Rd and Km most significantly inhibited activity in a dose-dependent manner, with IC50 values of 12.05±0.82 and 8.84±0.99 μM, respectively. Furthermore, the ginsenosides Rd and Km inhibited the TNF-α-induced expression levels of the COX-2 and iNOS gene in HepG2 cells. Air-dried leaf extracts and their chemical components, ginsenoside Rd and Km, are involved in the suppression of TNF-α-induced NF-κB activation and NF-κB-dependent iNOS and COX-2 gene expression. Consequently, air-dried leaf extract from PG, and the purified ginsenosides, have therapeutic potential as anti-inflammatory.
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RhoE is Frequently Down-regulated in Hepatocellular Carcinoma (HCC) and Suppresses HCC Invasion Through Antagonizing the Rho/Rho-kinase/myosin Phosphatase Target Pathway
Hepatology (Baltimore, Md.).
Jan, 2013 |
Pubmed ID: 22829315 Deregulation of Rho guanosine triphosphatase (GTPase) pathways plays an important role in tumorigenesis and metastasis of hepatocellular carcinoma (HCC). RhoE/Rnd3 belongs to an atypical subfamily of the RhoGTPase, the Rnd family, as it lacks the intrinsic GTPase activity and remains always in its active GTP-bound form. In this study we investigated the role of RhoE in HCC. We examined the expression of RhoE in primary HCC samples from patients predominantly infected with the hepatitis B virus (HBV) and found that the RhoE messenger RNA (mRNA) level was frequently down-regulated (83.1%, 59/71) in HCCs. Low expression of RhoE in the tumors was significantly associated with shorter disease-free survival (P = 0.020) of the patients. Knockdown of RhoE by short-hairpin RNA using a lentiviral approach led to increased cell motility and invasiveness in SMMC7721 and BEL7402 HCC cells. Moreover, in vivo an orthotopic liver injection model in nude mice further demonstrated that knockdown of RhoE enhanced local invasion of HCC cells in the livers, with more invasive tumor front and increased incidence of venous invasion. Mechanistically, stable knockdown of RhoE in HCC cells significantly enhanced the phosphorylation of myosin phosphatase, promoted assembly of stress fibers, and increased the formation of plasma membrane blebbings, all these changes and activities being associated with activation of the Rho/Rho-kinase (ROCK) pathway. CONCLUSION: RhoE was frequently down-regulated in predominantly HBV-associated HCCs and this down-regulation was associated with a more aggressive HCC phenotype. RhoE regulated the cytoskeleton remodeling and suppressed HCC motility and invasiveness by way of inhibiting the Rho/ROCK axis.
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Effect of Recreational Noise Exposure on Hearing Impairment Among Teenage Students
Research in Developmental Disabilities.
Jan, 2013 |
Pubmed ID: 22940166 Several studies have focused on the potential impact of children's hearing loss on learning and development. Recently, numerous teenage students have been found to be fond of listening to music on personal devices and participating in recreational music activities. The objective of this study was to investigate teenage students' hearing impairment, their experience with recreational noise exposure, and their self-reported hearing. The participants were 1878 first-year students at a university in Taiwan. The result of the pure tone audiometry test showed that 11.9% of the participants had one or two ears with a hearing threshold over 25 dB. Over the past year, approximately 80.9% of the participants had taken part in at least one loud-noise recreational activity, and 90.9% of the participants were in the habit of using earphones. Among the participants, 190 students with a high level of recreational noise exposure were assigned to the exposure group, and 191 students with a low level of recreational noise exposure constituted the control group. The exposure group had more hearing problems than the control group, but no significant difference existed between the two groups in the pure tone audiometry test (p=0.857). It is suggested that the schools should reinforce hearing health education and proactively provide intervention measures, such as hearing tests, evaluation of noise exposure, and hearing protection.
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Vagus Nerve Stimulation Modulates Visceral Pain-related Affective Memory
Behavioural Brain Research.
Jan, 2013 |
Pubmed ID: 22940455 Within a biopsychosocial model of pain, pain is seen as a conscious experience modulated by mental, emotional and sensory mechanisms. Recently, using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Electrical vagus nerve stimulation (VNS) has become an established therapy for treatment-resistant epilepsy. VNS has also been shown to enhance memory performance in rats and humans. High-intensity VNS (400 μA) immediately following conditional training significantly increases the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, VNS (400 μA) had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). Low-intensity VNS (40 μA) had no effect on CRD-induced CPA. Electrophysiological recording showed that VNS (400 μA) had no effect on basal and CRD-induced ACC neuronal firing. Further, VNS did not alter CRD-induced visceral pain responses suggesting high intensity VNS facilitates visceral pain aversive memory independent of sensory discriminative aspects of visceral pain processing. The findings that vagus nerve stimulation facilities visceral pain-related affective memory underscore the importance of memory in visceral pain perception, and support the theory that postprandial factors may act on vagal afferents to modulate ongoing nature of visceral pain-induced affective disorder observed in the clinic, such as irritable bowel syndrome.
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Evidence of Intracellular Stages in Trypanosoma (Megatrypanum) Theileri in Non-phagocytic Mammalian Cells
Veterinary Parasitology.
Jan, 2013 |
Pubmed ID: 23021263 Trypanosoma (subgenus Megatrypanum) theileri was first identified over one hundred years ago, and is a widespread parasite in cattle. Its life cycle within the mammalian host has rarely been reported. Whether there is an intracellular stage in tissues is unknown and such a stage has not been demonstrated experimentally. Intriguingly, using Giemsa staining with light microscopy and transmission electron microscopy examination, we found that the parasite was able not only to attach to cells but also to invade several phagocytic and non-phagocytic mammalian cells. Based on these findings, we conducted further investigations using a special antibody in immunofluorescence confocal images. Moreover, we examined a series of possible events of cell invasion in T. theileri. The results revealed that GM1, a marker of membrane rafts, was implicated in the mechanism of entry by this parasite. After incubation with tissue culture trypomastigotes, the gelatinolytic activity was significantly increased and accumulated at the attachment sites. Using ultrastructural localization detection by CytoTracker live imaging and confocal immunofluorescence microscopy, we found that lysosome fusion and the autophagy pathway were engaged in invaginating processes. T. theileri amastigotes also invaded cells and were enclosed by the lysosomes. Furthermore, tissue-cultured trypomastigotes were found to be capable of triggering intracellular free Ca(2+) transients and TGF-β-signaling. Our findings that intracellular amastigote stages exist in mammalian cells infected with T. theileri and that the invasion processes involved various host cell components and cell signalings were extremely surprising and warrant further investigation.
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Change in Flatfoot of Preschool-aged Children: a 1-year Follow-up Study
European Journal of Pediatrics.
Feb, 2013 |
Pubmed ID: 23132641 The main purpose of this study is to investigate the changes in the signs of flatfoot of preschool-aged children in a 1-year follow-up study. This study performed follow-up on a total of 580 preschool-aged children (boys, 297 children; girls, 283 children) with a median age of 54 (range 36-71 months), and the average follow-up period was 11.8 months. This study used the Chippaux-Smirak index (CSI) of footprint as the assessment tool, and CSI > 62.70 % was used as the standard for determining whether preschool-aged children suffered from flatfoot. The results showed that the signs of flatfoot of preschool-aged children improved with increasing age. At the 1-year follow-up, the average CSI was 5.1 % lower, and the proportion of children with flatfoot was 14 % lower. The follow-up on the change in the signs of flatfoot showed that 37.6 % of the children originally with flatfoot had improved to normal, verifying that flatfoot indeed improves with increasing age. However, the results also showed that 9.9 % of the children who originally had normal feet had developed flatfoot with increasing age, which deserves subsequent investigation. The results of the follow-up also showed that children who were relatively younger, male, obese, and experiencing excessive joint laxity were more likely to experience the signs of flatfoot. Conclusion: The 1-year follow-up found that some preschool-aged children with flatfoot may develop normal feet, while children with normal feet may begin to experience the signs. Relevant factors affecting flatfoot in preschool-aged children continue to require further clarification.
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Novel Anti-inflammatory Effects of Doxazosin in Rodent Models of Inflammation
Pharmacology.
2013 |
Pubmed ID: 23146878 Background: Doxazosin is an α(1)-adrenergic receptor antagonist for the treatment of high blood pressure and benign prostatic hyperplasia. Peripheral α-adrenergic receptors have been implicated in inflammation. Aim: To examine the anti-inflammatory effects of doxazosin in rodent models of inflammation. Method: The anti-inflammatory properties of doxazosin were investigated in 4 models. In all studies, drug treatment was administered 15 min prior to challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model, LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood samples were collected for analysis. In the LPS-induced pulmonary inflammation model, LPS was instilled intranasally. Four hours after challenge, the lungs were harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed-type hypersensitivity model, the mice were injected intravenously with sheep red blood cells, and rechallenged in the left footpad 7 days later. Drug treatment was given on day 6 and 7 just prior to the rechallenge. The thickness of hind footpads was measured at 15 min after rechallenge. In the thioglycollate-induced peritoneal monocyte infiltration model, mice were challenged with 3% thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1 analysis. Results: In animals challenged systemically and intranasally with LPS, doxazosin inhibited TNF-α and MCP-1 production, respectively. In the delayed-type hypersensitivity model, footpad swelling was inhibited by doxazosin. Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of thioglycollate-stimulated animals, though this effect was not statistically significant. Conclusion: This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.
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Decreased MicroRNA(miR)-145 and Increased MiR-224 Expression in T Cells from Patients with Systemic Lupus Erythematosus Involved in Lupus Immunopathogenesis
Clinical and Experimental Immunology.
Jan, 2013 |
Pubmed ID: 23199328 Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed miRNAs using real-time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant-expressed miRNAs was detected using real-time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR-145, miR-224, miR-513-5p, miR-150, miR-516a-5p, miR-483-5p and miR-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed miR-145 and over-expressed miR-224 were noted. We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with miR-145 suppressed STAT1 and miR-224 transfection suppressed API5 protein expression. Over-expression of miR-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR-145 and miR-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 (STAT)-1 expression in patients with SLE.
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Antiproliferative and Apoptotic Effects of Compounds from the Flower of Mammea Siamensis (Miq.) T. Anders. on Human Cancer Cell Lines
Bioorganic & Medicinal Chemistry Letters.
Jan, 2013 |
Pubmed ID: 23206866 On the search for anti-cancer compounds from Thai traditional herb medicines, a bioassay-guided fractionation and chemical investigation of the methanol extract of Mammea siamensis flower resulted in the isolation and identification of eight compounds (1-8) including a novel geranylated coumarin, namely mammeanoyl (2), and seven known compounds (1 and 3-8). The structure of new compound 2 was elucidated based on the extensive spectroscopic and chemical methods. Among the isolated compounds, three structurally related coumarins 3, 4, and 5 showed significant antiproliferative activities against human leukemia and stomach cancer cell lines. However, these compounds did not affect the cell viabilities of colon cancer, hepatoma, and normal skin fibroblast cell lines. Further analysis demonstrated that the morphological features of apoptosis including DNA fragmentation and chromatin condensation were observed in human leukemia HL-60 cells treated with compounds 3, 4, and 5. In addition, compound 3 led to caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP), and compound 3-induced DNA fragmentation was inhibited by caspase-specific inhibitors. These results suggest that compound 3, 4, and 5 exert antiproliferative actions through apoptotic cell death in leukemia cells and these compounds may have the potential to be developed into new anti-cancer drug candidates.
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Hyperglycemia is Associated with Enhanced Gluconeogenesis in a Rat Model of Permanent Cerebral Ischemia
Molecular and Cellular Endocrinology.
Mar, 2013 |
Pubmed ID: 23279876 Hyperglycemia is common after acute stroke. In the acute phase of stroke (within 24h), rats with permanent cerebral ischemia developed higher fasting blood glucose and insulin levels in association with up-regulation of hepatic gluconeogenic gene expression, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase. In addition, hepatic gluconeogenesis-associated positive regulators, such as FoxO1, CAATT/enhancer-binding proteins (C/EBPs), and cAMP responsive element-binding protein (CREB), were up-regulated. For insulin signaling transduction, phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1) at the tyrosine residue, Akt, and AMP-activated protein kinase (AMPK), were attenuated in the liver, while negative regulators of insulin action, including phosphorylation of p38, c-Jun N-terminal kinase (JNK), and insulin receptor substrate-1 (IRS1) at the serine residue, were increased. In addition, the brains of rats with stroke exhibited a reduction in phosphorylation of IRS1 at the tyrosine residue and Akt. Circulating cortisol, glucagon, C-reactive protein (CRP), monocyte chemoattractant protein 1 (MCP-1), and resistin levels were elevated, but adiponectin was reduced. Our data suggest that cerebral ischemic insults might modify intracellular and extracellular environments, favoring hepatic gluconeogenesis and the consequences of hyperglycemia.
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Adult Onset Global Loss of the Fto Gene Alters Body Composition and Metabolism in the Mouse
PLoS Genetics.
Jan, 2013 |
Pubmed ID: 23300482 The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake.
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Self-efficacy, Self-care Behavior, Anxiety, and Depression in Taiwanese with Type 2 Diabetes: A Cross-sectional Survey
Nursing & Health Sciences.
Jan, 2013 |
Pubmed ID: 23301516 The relationships between self-efficacy, self-care behavior, anxiety, and depression for Taiwanese individuals with type 2 diabetes were determined in this study. Depression and anxiety are common symptoms that can contribute toward adverse medical outcomes. A descriptive, cross-sectional, correlational design was used. The sample comprised 201 patients with type 2 diabetes from diabetes outpatient clinics at three teaching hospitals in Taiwan. The results of this study revealed that people with diabetes who had received diabetes health education, regularly made clinical visits, underwent treatment, and did not smoke demonstrated a high self-efficacy score (P 
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Real-time PCR Method for the Detection and Quantification of Acanthamoeba Species in Various Types of Water Samples
Parasitology Research.
Mar, 2013 |
Pubmed ID: 23306384 In this study, a quantitative real-time PCR was developed to detect and quantify Acanthamoeba spp. in various environmental water samples. The water samples were taken from watershed, water treatment plant, and three thermal spring recreation areas. The overall detection rate was 14.2 % (25/176) for Acanthamoeba spp. The percentages of samples containing Acanthamoeba spp. from river water, raw drinking water, and thermal spring water were 13 % (13/100), 25 % (7/28), and 10.4 % (5/48), respectively. Acanthamoeba spp. concentrations were determined according to SYBR Green quantitative real-time PCR. A plasmid-based standard curve was constructed to determine the Acanthamoeba concentration using dilution factors for achieving 1.36 × 10(9) gene copies per PCR for 18S rRNA gene in Acanthamoeba spp. The resulting concentrations varied by the type of water, in the range of 46-2.6 × 10(2) cells/l in positive raw drinking water, 2.7 × 10(2)-1.5 × 10(4) cells/l in river water, and 54-1.7 × 10(3) cells/l in thermal spring water. The presence of Acanthamoeba spp. in the raw drinking water samples was also found to have a significant difference with heterotrophic plate count. The presence of Acanthamoeba spp. in various aquatic environments may be a potential health hazard and must be further evaluated.
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Prediction and Analysis of Antibody Amyloidogenesis from Sequences
PloS One.
2013 |
Pubmed ID: 23308169 Antibody amyloidogenesis is the aggregation of soluble proteins into amyloid fibrils that is one of major causes of the failures of humanized antibodies. The prediction and prevention of antibody amyloidogenesis are helpful for restoring and enhancing therapeutic effects. Due to a large number of possible germlines, the existing method is not practical to predict sequences of novel germlines, which establishes individual models for each known germline. This study proposes a first automatic and across-germline prediction method (named AbAmyloid) capable of predicting antibody amyloidogenesis from sequences. Since the amyloidogenesis is determined by a whole sequence of an antibody rather than germline-dependent properties such as mutated residues, this study assess three types of germline-independent sequence features (amino acid composition, dipeptide composition and physicochemical properties). AbAmyloid using a Random Forests classifier with dipeptide composition performs well on a data set of 12 germlines. The within- and across-germline prediction accuracies are 83.10% and 83.33% using Jackknife tests, respectively, and the novel-germline prediction accuracy using a leave-one-germline-out test is 72.22%. A thorough analysis of sequence features is conducted to identify informative properties for further providing insights to antibody amyloidogenesis. Some identified informative physicochemical properties are amphiphilicity, hydrophobicity, reverse turn, helical structure, isoelectric point, net charge, mutability, coil, turn, linker, nuclear protein, etc. Additionally, the numbers of ubiquitylation sites in amyloidogenic and non-amyloidogenic antibodies are found to be significantly different. It reveals that antibodies less likely to be ubiquitylated tend to be amyloidogenic. The method AbAmyloid capable of automatically predicting antibody amyloidogenesis of novel germlines is implemented as a publicly available web server at http://iclab.life.nctu.edu.tw/abamyloid.
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Serum Polyfluoroalkyl Concentrations, Asthma Outcomes, and Immunological Markers in a Case-Control Study of Taiwanese Children
Environmental Health Perspectives.
Jan, 2013 |
Pubmed ID: 23309686 BACKGROUND: Perfluorinated compounds (PFCs) are ubiquitous pollutants. Experimental data suggest that they may be associated with adverse health outcomes, including asthma. However, there is little supporting epidemiological evidence. METHODS: A total of 231 asthmatic children and 225 non-asthmatic controls, all from Northern Taiwan, were recruited in the Genetic and Biomarker study for Childhood Asthma. Structure questionnaires were administered by face-to-face interview. Serum concentrations of 11 PFCs and levels of immunological markers were also measured. Associations of PFC quartiles with concentrations of immunological markers and asthma outcomes were estimated using multivariable regression models. RESULTS: Nine PFCs were detectable in most children (≥84.4%), of which perfluorooctane sulfonate (PFOS) was the most abundant (median serum concentration of 33.9 ng/mL in asthmatics and 28.9 ng/mL in controls). Adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFC exposure ranged from 1.81 (95%CI: 1.02, 3.23) for the perfluorododecanoic acid (PFDoA) to 4.05 (95%CI: 2.21, 7.42) for perfluorooctanic acid (PFOA). PFOS, PFOA, and subsets of the other PFCs were positively associated with serum IgE concentrations, absolute eosinophil counts (AEC), eosinophilic cationic protein (ECP) concentrations, and asthma severity scores among asthmatics. CONCLUSIONS: This study suggests an association between PFC exposure and juvenile asthma. Due to widespread exposure to these chemicals, these findings may be of potential public health concern.
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Factors Influencing Peritoneal Dialysis Patients' Psychosocial Adjustment
Journal of Clinical Nursing.
Jan, 2013 |
Pubmed ID: 23311545 AIMS AND OBJECTIVES: The specific aims of this study were as follows: (1) to describe psychosocial adjustment in adults with end-stage renal disease who underwent maintenance peritoneal dialysis; (2) to explore the influence of demographics, clinical variables, symptom distress and social support on psychosocial adjustment and (3) to determine predictive factors of psychosocial adjustment. BACKGROUND: Proper psychosocial adjustment is important for patients with end-stage renal disease to cope with multiple stressors of their disease and to balance their lives within the restrictions imposed by peritoneal dialysis treatment. Knowledge on psychosocial adjustment in patients receiving long-term peritoneal dialysis has been limited. DESIGN: The study was based on a predictive correlational design. METHOD: One hundred peritoneal dialysis patients were recruited from outpatient peritoneal dialysis clinics of a general hospital in Taipei, Taiwan. Data were collected with the study questionnaires, including the Physical Symptom Distress Scale, the Social Support Scale and the Psychosocial Adjustment to Illness Scale - self-report. RESULTS: The mean score on the Psychosocial Adjustment to Illness Scale was 359·7 (SD = 40·0), indicating that these participants were moderately struggling in adjusting to their illness. Symptom distress, family social support and financial status explained 38·3% of the variance in psychosocial adjustment (F(3,96)  = 21·5, pÂ
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Using Data to Attribute Episodes of Warming and Cooling in Instrumental Records
Proceedings of the National Academy of Sciences of the United States of America.
Feb, 2013 |
Pubmed ID: 23345448 The observed global-warming rate has been nonuniform, and the cause of each episode of slowing in the expected warming rate is the subject of intense debate. To explain this, nonrecurrent events have commonly been invoked for each episode separately. After reviewing evidence in both the latest global data (HadCRUT4) and the longest instrumental record, Central England Temperature, a revised picture is emerging that gives a consistent attribution for each multidecadal episode of warming and cooling in recent history, and suggests that the anthropogenic global warming trends might have been overestimated by a factor of two in the second half of the 20th century. A recurrent multidecadal oscillation is found to extend to the preindustrial era in the 353-y Central England Temperature and is likely an internal variability related to the Atlantic Multidecadal Oscillation (AMO), possibly caused by the thermohaline circulation variability. The perspective of a long record helps in quantifying the contribution from internal variability, especially one with a period so long that it is often confused with secular trends in shorter records. Solar contribution is found to be minimal for the second half of the 20th century and less than 10% for the first half. The underlying net anthropogenic warming rate in the industrial era is found to have been steady since 1910 at 0.07-0.08 °C/decade, with superimposed AMO-related ups and downs that included the early 20th century warming, the cooling of the 1960s and 1970s, the accelerated warming of the 1980s and 1990s, and the recent slowing of the warming rates. Quantitatively, the recurrent multidecadal internal variability, often underestimated in attribution studies, accounts for 40% of the observed recent 50-y warming trend.
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Defibrillation Success with High Frequency Electric Fields is Related to Degree and Location of Conduction Block
Heart Rhythm : the Official Journal of the Heart Rhythm Society.
Jan, 2013 |
Pubmed ID: 23354078 BACKGROUND: We recently demonstrated that high frequency alternating current (HFAC) electric fields can reversibly block propagation in the heart by inducing an oscillating, elevated transmembrane potential (V(m)) which maintains myocytes in a refractory state for the field duration, and can terminate arrhythmias, including ventricular fibrillation (VF). OBJECTIVE: In this study, we sought to quantify and characterize conduction block (CB) induced by HFAC fields and to determine whether the degree of CB can be used to predict defibrillation success. METHODS: Optical mapping was performed in adult guinea pig hearts (n = 14), and simulations were performed in an anatomically accurate rabbit ventricular model. HFAC fields (50-500 Hz) were applied to the ventricles. A novel power spectrum metric of CB - the loss of spectral power in the 1-30 Hz range, termed loss of conduction power (LCP) - was assessed during the HFAC field and compared with defibrillation success and VF vulnerability. RESULTS: LCP increased with field strength and decreased with frequency. Optical mapping experiments conducted on the epicardial surface showed that LCP and the size of CB regions were significantly correlated with VF initiation and termination. In simulations, sub-surface myocardial LCP and CB size were more closely correlated with VF termination than surface values. Multilinear regression analysis of simulation results revealed that while CB on both the surface and sub-surface myocardium were predictive, sub-surface myocardial CB was the better predictor of defibrillation success. CONCLUSION: HFAC fields induce a field-dependent state of conduction block, and defibrillation success is related to the degree and location of the conduction block.
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Inhibitory Effect on NO Production of Triterpenes from the Fruiting Bodies of Ganoderma Lucidum
Bioorganic & Medicinal Chemistry Letters.
Mar, 2013 |
Pubmed ID: 23357630 Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D(2) (2), butyl lucidenate E(2) (3) and butyl lucidenate Q (4) along with 11 known compounds (5-15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW 264.7 cells. Compounds 1, 3, 4, 9, 10 and 15 showed inhibitory potency with IC(50) values of 7.4, 6.4, 4.3, 9.4, 9.2 and 4.5μM, respectively. Compounds 1, 3 and 15 dose-dependently reduced the LPS-induced iNOS expressions. Preincubation of cell with 1, 3 and 15 significantly suppressed LPS-induced expression of COX-2 protein.
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Causes and Prevention of Sudden Cardiac Death in the Elderly
Nature Reviews. Cardiology.
Mar, 2013 |
Pubmed ID: 23358267 Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.
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Dynamic Large-scale Chromosomal Rearrangements Fuel Rapid Adaptation in Yeast Populations
PLoS Genetics.
Jan, 2013 |
Pubmed ID: 23358723 Large-scale genome rearrangements have been observed in cells adapting to various selective conditions during laboratory evolution experiments. However, it remains unclear whether these types of mutations can be stably maintained in populations and how they impact the evolutionary trajectories. Here we show that chromosomal rearrangements contribute to extremely high copper tolerance in a set of natural yeast strains isolated from Evolution Canyon (EC), Israel. The chromosomal rearrangements in EC strains result in segmental duplications in chromosomes 7 and 8, which increase the copy number of genes involved in copper regulation, including the crucial transcriptional activator CUP2 and the metallothionein CUP1. The copy number of CUP2 is correlated with the level of copper tolerance, indicating that increasing dosages of a single transcriptional activator by chromosomal rearrangements has a profound effect on a regulatory pathway. By gene expression analysis and functional assays, we identified three previously unknown downstream targets of CUP2: PHO84, SCM4, and CIN2, all of which contributed to copper tolerance in EC strains. Finally, we conducted an evolution experiment to examine how cells maintained these changes in a fluctuating environment. Interestingly, the rearranged chromosomes were reverted back to the wild-type configuration at a high frequency and the recovered chromosome became fixed in less selective conditions. Our results suggest that transposon-mediated chromosomal rearrangements can be highly dynamic and can serve as a reversible mechanism during early stages of adaptive evolution.
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Sustaining a Regional Emerging Infectious Disease Research Network: a Trust-based Approach
Emerging Health Threats Journal.
2013 |
Pubmed ID: 23362419 The Asia Partnership on Emerging Infectious Diseases Research (APEIR) was initiated in 2006 to promote regional collaboration in avian influenza research. In 2009, the partnership expanded its scope to include all emerging infectious diseases. APEIR partners include public health and animal researchers, officials and practitioners from Cambodia, China, Lao PDR, Indonesia, Thailand and Vietnam. APEIR has accomplished several major achievements in three key areas of activity: (i) knowledge generation (i.e., through research); (ii) research capacity building (e.g., by developing high-quality research proposals, by planning and conducting joint research projects, by adopting a broader Ecohealth/OneHealth approach); and (iii) policy advocacy (e.g., by disseminating research results to policy makers). This paper describes these achievements, with a focus on the partnership's five major areas of emerging infectious disease research: wild migratory birds, backyard poultry systems, socio-economic impact, policy analysis, and control measures. We highlight two case studies illustrating how the partnership's research results are being used to inform policy. We also highlight lessons learned after five years of working hard to build our partnership and the value added by a multi-country, multi-sectoral, multi-disciplinary research partnership like APEIR.
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Lower Body Negative Pressure-induced Vagal Reaction: Role for the Osmopressor Response?
American Journal of Hypertension.
Jan, 2013 |
Pubmed ID: 23382321 BACKGROUND Water ingestion elicits an osmopressor response in patients with impaired baroreflexes. In young, healthy subjects, water elicits sympathetic vasoconstriction. This study investigated the effect of water on the lower body negative pressure (LBNP)-induced vasovagal reaction and also analyzed its effect on the change of regional cerebral blood flow during LBNP. METHODS Twelve young healthy subjects underwent LBNP (40mm Hg) tolerance testing for 45 minutes or until presyncopal symptoms occurred. Subjects received either LBNP or no LBNP with or without prior water ingestion. The severity of vasovagal reaction was determined by participant self-report rating of orthostatic symptoms during the LBNP test. Changes of regional cerebral blood flow (rCBF) between LBNP and water ingestion with LBNP groups were assessed using statistical parametrical mapping analyses. RESULTS Water ingestion attenuated the severity of symptomatic scores during LBNP (P = 0.004). Water ingestion increased Total peripheral vascular resistance (P < 0.001) and attenuated the blood pressure drop (P < 0.001) at the cessation of study. LBNP decreased rCBF over the left superior prefrontal gyrus, limbic-parahippocampal gyrus, left sublobar-caudate body, and hypothalamus (P < 0.001). Water increased rCBF significantly over the right frontal lobe, including the inferior and medial prefrontal gyrus, subcallosal, and sublobar insula, during LBNP stimulation (P < 0.001). CONCLUSIONS Water ingestion strongly reduces symptomatic burden of the vasovagal reaction induced by LBNP stimulation. The cortical activation of limbic and prefrontal cortex likely indicates the involvement of osmopressor response in central autonomic cardiovascular physiology. The central cortical activation of osmopressor response might provide insight into the mechanisms by which water ingestion reduces the vasovagal reaction.
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Interleukin-13 Genetic Variants, Household Carpet Use and Childhood Asthma
PloS One.
2013 |
Pubmed ID: 23382814 Interleukin (IL)-13 genetic polymorphisms have shown adverse effects on respiratory health. However, few studies have explored the interactive effects between IL-13 haplotypes and environmental exposures on childhood asthma. The aims of our study are to evaluate the effects of IL-13 genetic variants on asthma phenotypes, and explore the potential interaction between IL-13 and household environmental exposures among Taiwanese children. We investigated 3,577 children in the Taiwan Children Health Study from 14 Taiwanese communities. Data regarding children's exposure and disease status were obtained from parents using a structured questionnaire. Four SNPs were tagged accounting for 100% of the variations in IL-13. Multiple logistic regression models with false-discovery rate (FDR) adjustments were fitted to estimate the effects of IL-13 variants on asthma phenotypes. SNP rs1800925, SNP rs20541 and SNP rs848 were significantly associated with increased risks on childhood wheeze with FDR of 0.03, 0.04 and 0.04, respectively. Children carrying two copies of h1011 haplotype showed increased susceptibility to wheeze. Compared to those without carpet use and h1011 haplotype, children carrying h1011 haplotype and using carpet at home had significantly synergistic risks of wheeze (OR, 2.5; 95% CI, 1.4-4.4; p for interaction, 0.01) and late-onset asthma (OR, 4.7; 95% CI, 2.0-10.9; p for interaction, 0.02). In conclusions, IL-13 genetic variants showed significant adverse effects on asthma phenotypes among children. The results also suggested that asthma pathogenesis might be mediated by household carpet use.
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Mechanism-based Facilitated Maturation of Human Pluripotent Stem Cell-derived Cardiomyocytes
Circulation. Arrhythmia and Electrophysiology.
Feb, 2013 |
Pubmed ID: 23392582 Background- Human embryonic stem cells (hESCs) can be efficiently and reproducibly directed into cardiomyocytes (CMs) using stage-specific induction protocols. However, their functional properties and suitability for clinical and other applications have not been evaluated. Methods and Results- Here we showed that CMs derived from multiple pluripotent human stem cell lines (hESC: H1, HES2) and types (induced pluripotent stem cell) using different in vitro differentiation protocols (embryoid body formation, endodermal induction, directed differentiation) commonly displayed immature, proarrhythmic action potential properties such as high degree of automaticity, depolarized resting membrane potential, Phase 4- depolarization, and delayed after-depolarization. Among the panoply of sarcolemmal ionic currents investigated (I(Na)(+)/I(CaL)(+)/I(Kr)(+)/I(NCX)(+)/I(f)(+)/I(to)(+)/I(K1)(-)/I(Ks)(-)), we pinpointed the lack of the Kir2.1-encoded inwardly rectifying K(+) current (I(K1)) as the single mechanistic contributor to the observed immature electrophysiological properties in hESC-CMs. Forced expression of Kir2.1 in hESC-CMs led to robust expression of Ba(2+)-sensitive I(K1) and, more importantly, completely ablated all the proarrhythmic action potential traits, rendering the electrophysiological phenotype indistinguishable from the adult counterparts. These results provided the first link of a complex developmentally arrested phenotype to a major effector gene, and importantly, further led us to develop a bio-mimetic culturing strategy for enhancing maturation. Conclusions- By providing the environmental cues that are missing in conventional culturing method, this approach did not require any genetic or pharmacological interventions. Our findings can facilitate clinical applications, drug discovery, and cardiotoxicity screening by improving the yield, safety, and efficacy of derived CMs.
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Concurrent Celecoxib with 5-fluorouracil/epirubicin/cyclophosphamide Followed by Docetaxel for Stages II - III Invasive Breast Cancer: the OOTR-N001 Study
Expert Opinion on Investigational Drugs.
Mar, 2013 |
Pubmed ID: 23394482 Objectives: This prospective study aimed at investigating the efficacy and safety of the concurrent use of celecoxib (CXB) with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), followed by docetaxel (T) in the neoadjuvant setting. Patients and methods: A total of 64 invasive breast cancer patients were recruited in the N001 Phase II, multicenter, open-label, single-arm study to receive four cycles of FEC (500, 100, 500 mg/m(2)) followed by four cycles of T (100 mg/m(2)) with concurrent CXB (200 mg b.i.d.) as neoadjuvant therapy (NAT). The combined chemotherapies were administered on day 1 of each cycle every 3 weeks. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). Quasi-pCR (QpCR), pCR and near pCR (npCR) were discussed considering their similar survival outcomes. ORR included clinical complete response (cCR) and clinical partial response (cPR). Secondary endpoints included safety, breast conservation rate and disease-free survival. Results: Between February 2006 and January 2010, 57 of 64 evaluable patients with luminal A (n = 35, 61.4%), luminal B (n = 12, 21.1%), HER-2 positive (n = 8, 14%) and triple-negative (n = 2, 3.5%) breast cancer completed NAT and surgery. QpCR rate was observed in 18 (31.6%) patients. Exclusive of triple-negative subtype, pCR (p = 0.761) did not differ compared to other subtypes, while npCR (p = 0.043) exhibited a difference. Patients with HER-2 overexpression had a significantly higher QpCR than those of the disease attribute (10/20 vs 8/37, p = 0.029). After NAT, 43 (75.4%) and 13 (22.8%) patients achieved cCR and cPR, respectively. Patients responding to FEC were more likely to achieve a better ORR after subsequent T (p = 0.004). Over 80% of all patients received breast-conserving therapy (BCT) after receiving NAT, and 11 of 14 (78.6%) patients with T3 tumor at diagnosis became eligible for BCT after NAT. A total of 60 patients completed ≥ 6 cycles of NAT, followed by surgery; at a median follow-up of 50 months, 80% of the patients are disease-free. Neither drug-induced life-threatening toxicity nor cardiotoxicity was observed. Conclusions: Neoadjuvant use of FEC-T with concurrent CXB is active and safe for treatment of operable invasive breast cancer. The ORR was higher, but QpCR was comparable to other studies. Most patients are still disease-free, and BCT became an option for the females. Further clinical and translational studies on the use of cyclooxygenase-2 inhibitors with neoadjuvant chemotherapy are warranted.
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Reversible Sol-to-Gel Transformation of Uracil Gelators: Specific Colorimetric and Fluorimetric Sensor for Fluoride Ions
Langmuir : the ACS Journal of Surfaces and Colloids.
Feb, 2013 |
Pubmed ID: 23394550 A new type of anthracene organogelator based on uracil was obtained using organic aromatic solvents, cyclohexane, DMSO, ethanol, and ethyl acetate. It was further characterized by field-emission scanning electron microscopy and transmission electron microscopy. Specifically, the resulting organogels were demonstrated to be promising colorimetric and fluorescent sensors toward fluoride ions with high sensitivity and selectivity, accompanying the disruption of the gelators. Spectroscopic study and (1)H NMR titration experiment revealed that the deprotonation of the hydrogen atom on the N position of uracil moiety by fluoride ions is responsible for the recognition events, evidenced by immediate transformation from the sol phase to the gel state upon adding a small amount of a proton solvent, methanol. The process is reversible, with zero loss in sensing activity and sol-to-gel transformation ability even after five runs.
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Cost of Treatment for Breast Cancer in Central Vietnam
Global Health Action.
2013 |
Pubmed ID: 23394855 Background: In recent years, cases of breast cancer have been on the rise in Vietnam. To date, there has been no study on the financial burden of the disease. This study estimates the direct medical cost of a 5-year treatment course for women with primary breast cancer in central Vietnam. Methods: Retrospective patient-level data from medical records at the Hue Central Hospital between 2001 and 2006 were analyzed. Cost analysis was conducted from the health care payers' perspective. Various direct medical cost categories were computed for a 5-year treatment course for patients with breast cancer. Costs, in US dollars, discounted at a 3% rate, were converted to 2010 after adjusting for inflation. For each cost category, the mean, standard deviation, median, and cost range were estimated. Median regression was used to investigate the relationship between costs and the stage, age at diagnosis, and the health insurance coverage of the patients. Results: The total direct medical cost for a 5-year treatment course for breast cancer in central Vietnam was estimated at $975 per patient (range: $11.7-$3,955). The initial treatment cost, particularly the cost of chemotherapy, was found to account for the greatest proportion of total costs (64.9%). Among the patient characteristics studied, stage at diagnosis was significantly associated with total treatment costs. Patients at later stages of breast cancer did not differ significantly in their total costs from those at earlier stages however, but their survival time was much shorter. The absence of health insurance was the main factor limiting service uptake. Conclusion: From the health care payers' perspective, the Government subsidization of public hospital charges lowered the direct medical costs of a 5-year treatment course for primary breast cancer in central Vietnam. However, the long treatment course was significantly influenced by out-of-pocket payments for patients without health insurance.
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Clinical and Microbiological Features of Shewanella Bacteremia in Patients with Hepatobiliary Disease
Internal Medicine (Tokyo, Japan).
2013 |
Pubmed ID: 23411697 Objective Shewanella bacteremia is an uncommon but potentially fatal disease. Although hepatobiliary diseases have been proposed to be risk factors for various Shewanella infections, little is known about the features of Shewanella bacteremia in patients with hepatobiliary diseases. This study aims to characterize the presentation and risk factors of Shewanella bacteremia in patients with hepatobiliary diseases. Methods We retrospectively investigated the clinical features, microbiology and outcomes of patients with Shewanella bacteremia who were admitted to a tertiary medical center between January 2001 and December 2010. All isolates were confirmed to the species level using 16S rRNA sequencing analyses. The English language medical literature was searched for previously published reports. Results Fifty-nine cases of Shewanella bacteremia, including nine at the hospital, were identified, 28 (47.4%) of which involved underlying hepatobiliary diseases, representing an important risk factor. In 12 of the 28 cases, the infections involved the hepatobiliary system; with a tendency towards an Asian origin. In our case series of nine patients, Shewanella haliotis was isolated in five patients. The majority of our patients lived in coastal areas, consumed seafood regularly and developed bacteremia during the summer season. Conclusion It is recommended that the possibility for Shewanella infection be considered in patients with bacteremia and also underlying hepatobiliary diseases, particularly if patients present with hepatobiliary infections, a history of seafood, or development of the disease during the summer.
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Frequency of Premature Menopause in Women Who Carry a BRCA1 or BRCA2 Mutation
Fertility and Sterility.
Feb, 2013 |
Pubmed ID: 23414920 OBJECTIVE: To evaluate the impact of carrying a BRCA1 or BRCA2 mutation on the probability of experiencing premature natural menopause. DESIGN: Observational study. SETTING: Patients in an academic research environment. PATIENT(S): Women who carry a BRCA1 or BRCA2 mutation (case subjects) and women who do not carry a mutation (control subjects). INTERVENTION(S): Survey about reproductive history administered on study entry and every 2 years thereafter. MAIN OUTCOME MEASURE(S): The impact of carrying a BRCA mutation on age at menopause and other factors, including parity, age at first birth, age at last birth, and self-reported fertility. RESULT(S): A total of 908 matched pairs were identified. The mean age at natural menopause was 48.8 years for BRCA1 carriers, 49.2 years for BRCA2 carriers, and 50.3 years for control subjects. Women who carried a BRCA mutation had parity similar to noncarriers and were as likely as noncarriers to have a child after age 35 years. Similar proportions reported a history of fertility problems (12.5% vs. 13.7%) and use of fertility medication (6.0% vs. 7.0%). CONCLUSION(S): Women who carry a BRCA mutation experience menopause earlier, on average, than women who do not have a mutation, but the difference is small and does not appear to affect fertility.
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Young Adult Daughters of BRCA1/2 Positive Mothers: What Do They Know About Hereditary Cancer and How Much Do They Worry?
Psycho-oncology.
Feb, 2013 |
Pubmed ID: 23417902 OBJECTIVE: The objectives of this study are to determine (i) what daughters, ages 18-24 years, of BRCA1/2 mutation carriers understand about their 50% chance of carrying a BRCA1/2 mutation and about risk reduction or management options for mutation carriers, (ii) the extent and nature of daughters' cancer-related distress, and (iii) the effects of knowing mother's mutation status on daughters' future plans. METHODS: A total of 40 daughters, currently aged 18-24 years, of mothers who tested positive for a mutation in BRCA1/2 were invited by mail to participate (with contact information supplied by their mothers). Daughters participated in a qualitative telephone interview about the impact of learning their mother's mutation status on their understanding of their own cancer risks and their cancer-related distress, and their knowledge of screening strategies, risk-reducing surgery, current health status, and future plans. Participants also completed study-specific demographic and family history questionnaires, the Brief Symptom Inventory-18, Impact of Event Scale (with hereditary predisposition to breast/ovarian cancer as the event), and the Breast Cancer Genetic Counseling Knowledge Questionnaire. RESULTS: Daughters' genetic knowledge is suboptimal; gaps and misconceptions were common. Over 1/3 of the daughters reported high cancer-related distress, despite normal levels of general distress. Disclosed genetic information raised future concerns, especially regarding childbearing. CONCLUSION: Targeted professional attention to this high-risk cohort of young women is critical to inform the next generation of daughters of BRCA1/2 mutation carriers and encourage recommended screening by age 25 years. Improved uptake of screening and risk reduction options could improve survival, and psychoeducation could reduce cancer-related distress. Copyright © 2013 John Wiley & Sons, Ltd.
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Phosphatidylserine Recognition and Induction of Apoptotic Cell Clearance by Drosophila Engulfment Receptor Draper
Journal of Biochemistry.
Feb, 2013 |
Pubmed ID: 23420848 The membrane phospholipid phosphatidylserine is exposed on the cell surface during apoptosis and acts as an eat-me signal in the phagocytosis of apoptotic cells in mammals and nematodes. However, whether this is also true in insects was unclear. When milk fat globule-EGF-factor 8, a phosphatidylserine-binding protein of mammals, was ectopically expressed in Drosophila, the level of phagocytosis was reduced whereas this was not the case for the same protein lacking a domain responsible for the binding to phosphatidylserine. We found that the extracellular region of Draper, an engulfment receptor of Drosophila, binds to phosphatidylserine in an enzyme-linked immunosorbent assay-like solid-phase assay as well as in an assay for surface plasmon resonance. A portion of Draper containing domains EMI and NIM located close to the N-terminus was required for the binding to phosphatidylserine, and a Draper protein lacking this region was not active in Drosophila. Finally, the level of tyrosine-phosphorylated Draper, indicative of the activation of Draper, in a hemocyte-derived cell line was increased after treatment with phosphatidylserine-containing liposome. These results indicated that phosphatidylserine serves as an eat-me signal in the phagocytic removal of apoptotic cells in Drosophila, and that Draper is a phosphatidylserine-binding receptor for phagocytosis.
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Pancreatic Cancer-Associated Cathepsin E As a Drug Activator
Journal of Controlled Release : Official Journal of the Controlled Release Society.
Feb, 2013 |
Pubmed ID: 23422726 Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat, and better means to detect and/or treat pancreatic cancer are urgently needed to save lives. Cathepsin E (Cath E) is a proteolytic enzyme highly expressed in PDAC. In this study, a novel approach using Cath E activation of a Cath E-specific prodrug was demonstrated. Specific activation of the prodrug is expected to kill pancreatic cancer cells without harming normal pancreatic cells. A novel 5-aminolevulinic acid (5-ALA) prodrug was custom-designed to be activated selectively by endogenous Cath E within the PDAC cells. The 5-ALA prodrug was incubated with Cath E-positive and -negative tumor cells and illuminated with various doses of light. In addition, mice genetically engineered to develop PDAC were injected intravenously with the 5-ALA prodrug, and the pancreas was treated with light irradiation. One day after treatment, PDAC tissue was assessed for apoptosis. The 5-ALA prodrug was activated within the Cath E-positive tumor but not in the normal pancreatic tissue. When used in combination with light treatment, it allowed delivery of selective photodynamic therapy (PDT) to the cancerous tissues, with minimal harm to the adjacent normal tissues. With this novel Cath E activation approach, it is possible to detect pancreatic cancer cells accurately and specifically impair their viability, while sparing normal cells. This treatment could result in fewer side effects than the non-specific treatments currently in use. Cath E is a specific and effective drug activator for PDAC treatment.
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Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya Japonica in Human Leukemia Cell Lines
International Journal of Molecular Sciences.
2013 |
Pubmed ID: 23429195 Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G(1) phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (∆ψ(m)) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia.
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Quantitative Detection and Identification of Naegleria Spp. in Various Environmental Water Samples Using Real-time Quantitative PCR Assay
Parasitology Research.
Feb, 2013 |
Pubmed ID: 23430358 Naegleria spp. is a free-living amoeba that can be found in various aquatic environments. There are some Naegleria spp. that can cause fatal infections in animals and humans, and the most important source of infection is through direct water contact. In this study, a real-time quantitative PCR was developed to detect and quantify the Naegleria spp. in various environmental water samples. The water samples were taken from rivershed, water treatment plants, and thermal spring recreation areas. The total detection rate was 4.0Â % (7/176) for Naegleria spp. The percentages of samples containing Naegleria spp. from river water, raw drinking water, and thermal spring water were 0Â % (0/100), 10.7Â % (3/28) and 8.3Â % (4/48), respectively. The concentration of Naegleria spp. in detected positive raw drinking water and thermal spring water samples was in the range of 3.9-12.6 and 1.1-24.2Â cells/L, respectively. The identified species included Naegleria australiensis, Naegleria lovaniensis, and Naegleria spitzbergeniensis. The presence of Naegleria spp. in various aquatic environments is considered a potential public health threat.
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Functions of the DExD/H-box Proteins in Nuclear Pre-mRNA Splicing
Biochimica Et Biophysica Acta.
Feb, 2013 |
Pubmed ID: 23454554 In eukaryotes, many genes are transcribed as precursor messenger RNAs (pre-mRNAs) that contain exons and introns, the latter of which must be removed and exons ligated to form the mature mRNAs. This process is called pre-mRNA splicing, which occurs in the nucleus. Although the chemistry of pre-mRNA splicing is identical to that of the self-splicing Group II introns, hundreds of proteins and five small nuclear RNAs (snRNAs), U1, U2, U4, U5, and U6, are essential for executing pre-mRNA splicing. Spliceosome, arguably the most complex cellular machine made up of all those proteins and snRNAs, is responsible for carrying out pre-mRNA splicing. In contrast to the transcription and the translation machineries, spliceosome is formed anew onto each pre-mRNA and undergoes a series of highly coordinated reconfigurations to form the catalytic center. This amazing process is orchestrated by a number of DExD/H-proteins that are the focus of this article, which aims to review the field in general and to project the exciting challenges and opportunities ahead. This article is part of a Special Issue entitled: The Biology of RNA helicases - Modulation for life.
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Aryl Hydrocarbon Receptor Controls Murine Mast Cell Homeostasis
Blood.
Apr, 2013 |
Pubmed ID: 23462117 We propose that the aryl hydrocarbon receptor (AhR), a unique chemical sensor, is critical in controlling mast cell differentiation, growth, and function in vitro and in vivo. In antigen-stimulated mast cells, exposure to AhR ligands resulted in a calcium- and reactive oxygen species (ROS)-dependent increase of reversible oxidation in and reduced activity of SHP-2 phosphatase, leading to enhanced mast cell signaling, degranulation, and mediator and cytokine release, as well as the in vivo anaphylactic response. Surprisingly, significant mast cell deficiency was noted in AhR-null mice due to defective calcium signaling and mitochondrial function, concomitant with reduced expression of c-kit and cytosolic STAT proteins, as well as enhanced intracellular ROS and apoptosis. Consequently, AhR-null mast cells responded poorly to stimulation, demonstrating a critical role of AhR signaling in maintaining mast cell homeostasis.
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Bovine Lactoferrin Inhibits Lung Cancer Growth Through Suppression of Both Inflammation and Expression of Vascular Endothelial Growth Factor
Journal of Dairy Science.
Apr, 2013 |
Pubmed ID: 23462173 Lung cancers are among the most common cancers in the world, and the search for effective and safe drugs for the chemoprevention and therapy of pulmonary cancer has become important. In this study, bovine lactoferrin (bLF) was used in both in vitro and in vivo approaches to investigate its activity against lung cancer. A human lung cancer cell line, A549, which expresses a high level of vascular endothelial growth factor (VEGF) under hypoxia, was used as an in vitro system for bLF treatment. A strain of transgenic mice carrying the human VEGF-A165 (hVEGF-A165) gene, which induces pulmonary tumors, was used as an in vivo lung cancer therapy model. We found that bLF significantly decreased proliferation of A549 cells by decreasing the expression of VEGF protein in a dose-dependent manner. Furthermore, oral administration of bLF at 300 mg/kg of body weight 3 times a week for 1.5 mo to the transgenic mice overexpressing hVEGF-A165 significantly eliminated expression of hVEGF-A165 and suppressed the formation of tumors. Additionally, treatment with bLF significantly decreased the levels of proinflammatory cytokines, such as tumor necrosis factor-α, and antiinflammatory cytokines, such as IL-4 and IL-10. Levels of IL-6, which is both a proinflammatory and an antiinflammatory cytokine, were also reduced. Treatment with bLF decreased levels of tumor necrosis factor-α, IL-4, IL-6, and IL-10 cytokines, resulting in limited inflammation, which then restricted growth of the lung cancer. Our results revealed that bLF is an inhibitor of angiogenesis and blocks lung cell inflammation; as such, it has considerable potential for therapeutic use in the treatment of lung cancer.
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Rise of the RNA Machines: Exploring the Structure of Long Non-Coding RNAs
Journal of Molecular Biology.
Mar, 2013 |
Pubmed ID: 23467124 Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are emerging in critical aspects of gene regulation. Thousands of lncRNAs have been recently discovered in a wide range of mammalian systems, related to development, epigenetics, cancer, brain function and hereditary disease. The structural biology of these lncRNAs presents a brave new RNA world, which may contain a diverse zoo of new architectures and mechanisms. While structural studies of lncRNAs are in their infancy, we describe existing structural data for lncRNAs, as well as crystallographic studies of other RNA machines and their implications for lncRNAs. We also discuss the importance of dynamics in RNA machine mechanism. Determining commonalities between lncRNA systems will help elucidate the evolution and mechanistic role of lncRNAs in disease, creating a structural framework necessary to pursue lncRNA-based therapeutics.
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Prognostic Impact of Inappropriate Defibrillator Shocks in a Population Cohort
Heart (British Cardiac Society).
Mar, 2013 |
Pubmed ID: 23468515 BACKGROUND: There is a relative paucity of data linking inappropriate implantable cardioverter-defibrillator (ICD) shocks to adverse clinical outcomes. OBJECTIVE: To examine the association between inappropriate ICD shocks and mortality or heart transplantation in a large population cohort. DESIGN, SETTING, PATIENTS: A cohort study which included all subjects who underwent ICD implantation between 1998 and 2008 and were followed up at our institution. MAIN OUTCOME MEASURES: Multivariable Cox regression analyses were conducted to investigate the effect of inappropriate shocks on the risk of death and heart transplantation. Appropriate and inappropriate ICD therapies were modelled as time-dependent covariates. RESULTS: A total of 1698 patients were included. During a median follow-up of 30 months, there were 246 (14.5%) deaths and 42 (2.5%) heart transplants. The incidence of inappropriate shocks was 10% at 1 year and 14% at 2 years. In the adjusted model, inappropriate shocks were not associated with death or transplantation (HR=0.97, 95% CI 0.70 to 1.36, p value=0.873). In contrast, appropriate shocks were associated with adverse outcomes (HR=3.11, 95% CI 2.41 to 4.02, p value
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Genome-wide Analysis Points to Roles for Extracellular Matrix Remodeling, the Visual Cycle, and Neuronal Development in Myopia
PLoS Genetics.
Feb, 2013 |
Pubmed ID: 23468642 Myopia, or nearsightedness, is the most common eye disorder, resulting primarily from excess elongation of the eye. The etiology of myopia, although known to be complex, is poorly understood. Here we report the largest ever genome-wide association study (45,771 participants) on myopia in Europeans. We performed a survival analysis on age of myopia onset and identified 22 significant associations ([Formula: see text]), two of which are replications of earlier associations with refractive error. Ten of the 20 novel associations identified replicate in a separate cohort of 8,323 participants who reported if they had developed myopia before age 10. These 22 associations in total explain 2.9% of the variance in myopia age of onset and point toward a number of different mechanisms behind the development of myopia. One association is in the gene PRSS56, which has previously been linked to abnormally small eyes; one is in a gene that forms part of the extracellular matrix (LAMA2); two are in or near genes involved in the regeneration of 11-cis-retinal (RGR and RDH5); two are near genes known to be involved in the growth and guidance of retinal ganglion cells (ZIC2, SFRP1); and five are in or near genes involved in neuronal signaling or development. These novel findings point toward multiple genetic factors involved in the development of myopia and suggest that complex interactions between extracellular matrix remodeling, neuronal development, and visual signals from the retina may underlie the development of myopia in humans.
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Electrofluidic Pressure Sensor Embedded Microfluidic Device: a Study of Endothelial Cells Under Hydrostatic Pressure and Shear Stress Combinations
Lab on a Chip.
May, 2013 |
Pubmed ID: 23475014 Various microfluidic cell culture devices have been developed for in vitro cell studies because of their capabilities to reconstitute in vivo microenvironments. However, controlling flows in microfluidic devices is not straightforward due to the wide varieties of fluidic properties of biological samples. Currently, flow observations mainly depend on optical imaging and macro scale transducers, which usually require sophisticated instrumentation and are difficult to scale up. Without real time monitoring, the control of flows can only rely on theoretical calculations and numerical simulations. Consequently, these devices have difficulty in being broadly exploited in biological research. This paper reports a microfluidic device with embedded pressure sensors constructed using electrofluidic circuits, which are electrical circuits built by fluidic channels filled with ionic liquid. A microfluidic device culturing endothelial cells under various shear stress and hydrostatic pressure combinations is developed to demonstrate this concept. The device combines the concepts of electrofluidic circuits for pressure sensing, and an equivalent circuit model to design the cell culture channels. In the experiments, human umbilical vein endothelial cells (HUVECs) are cultured in the device with a continuous medium perfusion, which provides the combinatory mechanical stimulations, while the hydrostatic pressures are monitored in real time to ensure the desired culture conditions. The experimental results demonstrate the importance of real time pressure monitoring, and how both mechanical stimulations affect the HUVEC culture. This developed microfluidic device is simple, robust, and can be easily scaled up for high-throughput experiments. Furthermore, the device provides a practical platform for an in vitro cell culture under well-controlled and dynamic microenvironments.
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PAX2 Expression in Ovarian Cancer
International Journal of Molecular Sciences.
2013 |
Pubmed ID: 23502471 PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty.
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Semiautomated Quantification of β-zone Parapapillary Atrophy Using Blue Light Fundus Autofluorescence
Acta Ophthalmologica.
Mar, 2013 |
Pubmed ID: 23506312 Purpose:  To evaluate the reproducibility of measurements of area of β-zone parapapillary atrophy (β-PPA) using blue laser fundus autofluorescence (FAF) and confocal scanning laser ophthalmoscopy reflectance (CSLO) measurements and to assess agreement between the two imaging modalities. Methods:  Sixty-five eyes of 45 patients (mean age, 68.2 ± 11.3 years) with established or suspected glaucoma from the Diagnostic Innovations in Glaucoma Study (DIGS) were prospectively included. FAF scans were obtained with the Spectralis HRA+OCT and CSLO reflectance images with the HRTII (both from Heidelberg Engineering, Heidelberg, Germany). Two masked graders independently measured β-PPA area on 3 consecutive scans using the semi-automated BluePeak RegionFinder software (BPRF) and on CSLO reflectance images using the optic disc contour line. Reproducibility of β-PPA area measurements was assessed using intraclass correlation coefficients (ICC). Results:  Intragrader reproducibility was 0.997 (95% CI, 0.996-0.998) and 0.995 (95% CI, 0.992-0.996) for grader 1 and 2, respectively, using FAF-BPRF, and by CSLO, it was 0.991 (95% CI, 0.986-0.994) and 0.988 (95% CI, 0.982-0.992). Intergrader agreement (ICC) was 0.53 (95% CI, 0.331-0.685) for FAF-BPRF and 0.404 (95% CI, 0.149-0.601) for CSLO (comparison between ICC, p = 0.368). Agreement (ICC) between the two devices was worse for grader 1 (0.356; 95% CI, 0.129-0.549) than grader 2 (0.856; 95% CI, 0.774-0.910) (p 
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Surveyed Data for Structural Shielding Calculations of Radiographic X-ray Installations in Taiwan
Health Physics.
May, 2013 |
Pubmed ID: 23528275 The use of surveyed data on the x-ray tube workloads and clinical exposure parameters was suggested in NCRP Report No. 147 for the structural shielding design of medical x-ray installations. To guide the shielding design of radiographic x-ray rooms in Taiwan, a large-scale survey was conducted to collect information required for the computations of the transmissions from broad x-ray beams through shielding materials. Surveyed data were collected during one week from 10,750 projections of 6,657 examinations in 13 radiographic rooms from nine hospitals. This survey was the first time that this type of clinical data has been collected in Taiwan on a large scale. The surveyed total workload was divided into separate contributions from x-ray projections directed at the floor, the wall bucky, and all barriers (used for secondary barriers). Based on the surveyed workload distributions, the unshielded air kerma per patient at 1 m from the source was calculated by the PCXMC program using surveyed x-ray tube parameters on the generator waveform, anode material, target angle, and filtration. Subsequently, the transmissions of x-rays through different barrier materials were computed by considering the average workloads and the average workloads plus one standard deviations. The latter computations were for a sensitivity study to find the influence of workload variations in different hospitals on the shielding requirements. All surveyed data and calculated results were compared with corresponding values given in NCRP 147 to analyze the radiographic imaging differences between Taiwan and U.S.
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Incidence, Clinical Characteristics, and Natural History of Pediatric IBD in Wisconsin: a Population-based Epidemiological Study
Inflammatory Bowel Diseases.
Mar, 2013 |
Pubmed ID: 23528339 BACKGROUND:: Epidemiological studies of pediatric inflammatory bowel diseases (IBD) are needed to generate etiological hypotheses and inform public policy; yet, rigorous population-based studies of the incidence and natural history of Crohn's disease (CD) and ulcerative colitis (UC) in the United States are limited. METHODS:: We developed a field-tested prospective system for identifying all new cases of IBD among Wisconsin children over an 8-year period (2000-2007). Subsequently, at the end of the study period, we retrospectively reconfirmed each case and characterized the clinical course of this incident cohort. RESULTS:: The annual incidence of IBD among Wisconsin children was 9.5 per 100,000 (6.6 per 100,000 for CD and 2.4 per 100,000 for UC). Approximately 19% of incident cases occurred in the first decade of life. Over the 8-year study period, the incidence of both CD and UC remained relatively stable. Additionally, (1) childhood IBD affected all racial groups equally, (2) over a follow-up of 4 years, 17% of patients with CD and 13% of patients with patients with UC required surgery, and (3) 85% and 40% of children with CD were treated with immunosuppressives and biologics, respectively, compared with 62% and 30% of patients with UC. CONCLUSIONS:: As in other North American populations, these data confirm a high incidence of pediatric-onset IBD. Importantly, in this Midwestern U.S. population, the incidence of CD and UC seems to be relatively stable over the last decade. The proportions of children requiring surgery and undergoing treatment with immunosuppressive and biological medications underscore the burden of these conditions.
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Identification and Quantitative Detection of Legionella Spp. in Various Aquatic Environments by Real-time PCR Assay
Environmental Science and Pollution Research International.
Mar, 2013 |
Pubmed ID: 23536272 In this study, a SYBR green quantitative real-time PCR was developed to quantify and detect the Legionella spp. in various environmental water samples. The water samples were taken from watershed, water treatment plant, and thermal spring area in Taiwan. Legionella was detected in 13.6 % (24/176), and the detection rate for river water, raw drinking water, and thermal spring water was 10, 21.4, and 16.6 %, respectively. Using real-time PCR, concentration of Legionella spp. in detected samples ranged between 9.75 × 10(4) and 3.47 × 10(5) cells/L in river water, 6.92 × 10(4) and 4.29 × 10(5) cells/L in raw drinking water, and 5.71 × 10(4) and 2.12 × 10(6) cells/L for thermal spring water samples. The identified species included Legionella pneumophila (20.8 %), Legionella jordanis (4.2 %), Legionella nautarum (4.2 %), Legionella sp. (4.2 %), and uncultured Legionella sp. (66.6 %). The presence of L. pneumophila in aquatic environments suggested a potential public health threat that must be further examined.
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Genome-wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
PLoS Genetics.
2013 |
Pubmed ID: 23544013 BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
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Social Environment Influences the Relationship Between Genotype and Gene Expression in Wild Baboons
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.
May, 2013 |
Pubmed ID: 23569293 Variation in the social environment can have profound effects on survival and reproduction in wild social mammals. However, we know little about the degree to which these effects are influenced by genetic differences among individuals, and conversely, the degree to which social environmental variation mediates genetic reaction norms. To better understand these relationships, we investigated the potential for dominance rank, social connectedness and group size to modify the effects of genetic variation on gene expression in the wild baboons of the Amboseli basin. We found evidence for a number of gene-environment interactions (GEIs) associated with variation in the social environment, encompassing social environments experienced in adulthood as well as persistent effects of early life social environment. Social connectedness, maternal dominance rank and group size all interacted with genotype to influence gene expression in at least one sex, and either in early life or in adulthood. These results suggest that social and behavioural variation, akin to other factors such as age and sex, can impact the genotype-phenotype relationship. We conclude that GEIs mediated by the social environment are important in the evolution and maintenance of individual differences in wild social mammals, including individual differences in responses to social stressors.
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Response to Stress in Early Tumor Colonization Modulates Switching of CD133-positive and CD133-negative Subpopulations in a Human Metastatic Colon Cancer Cell Line, SW620
PloS One.
2013 |
Pubmed ID: 23577199 According to the cancer stem cell (CSC) model, higher CD133 expression in tumor tissue is associated with metastasis and poor prognosis in colon cancer. As such, the CD133-positive (CD133(+)) subpopulation of cancer cells is believed to play a central role in tumor development and metastatic progression. Although CD133(+) cells are believed to display more CSC-like behavior and be solely responsible for tumor colonization, recent research indicates that CD133(-) cells from metastatic colon tumors not only also possess colonization capacity but also promote the growth of larger tumors in a mouse model than CD133(+) cells, suggesting that an alternative mechanism of metastasis exists. This study investigated this possibility by examining the cell viability, tumorigenicity, and proliferation and growth capacity of the CD133(+) and CD133(-) subpopulations of the SW620 cell line, a human metastatic colon cancer cell line, in both an in vitro cell model and an in vivo mouse model. While both SW620 (CD133-) and SW620(CD133+) cells were found to engage in bidirectional cell-type switching in reaction to exposure to environmental stressors, including hypoxia, a cell adhesion-free environment, and extracellular matrix stimulation, both in vitro and in vivo, CD133(-) cells were found to have a growth advantage during early colonization due to their greater resistance to proliferation inhibition. Based on these findings, a hypothetical model in which colon cancer cells engage in cell-type switching in reaction to exposure to environmental stressors is proposed. Such switching may provide a survival advantage during early colonization, as well as that explain previous conflicting observations.
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Alterations in Resting Functional Connectivity Due to Recent Motor Task
NeuroImage.
Sep, 2013 |
Pubmed ID: 23583747 The impact of recent experiences of task performance on resting functional connectivity MRI (fcMRI) has important implications for the design of many neuroimaging studies, because, if an effect is present, the fcMRI scan then must be performed before any evoked fMRI or after a time gap to allow it to dissipate. The present study aims to determine the effect of simple button presses, which are used in many cognitive fMRI tasks as a response recording method, on later acquired fcMRI data. Human volunteers were subject to a 23-minute button press motor task. Their resting-state brain activity before and after the task was assessed with fcMRI. It was found that, compared to the pre-task resting period, the post-task resting fcMRI revealed a significantly higher (p=0.002, N=24) cross correlation coefficient (CC) between left and right motor cortices. These changes were not present in sham control studies that matched the paradigm timing but had no actual task. The amplitude of fcMRI signal fluctuation (AF) also demonstrated an increase in the post-task period compared to pre-task. These changes were observed using both the right-hand-only task and the two-hand task. Study of the recovery time course of these effects revealed that the CC changes lasted for about 5min while the AF change lasted for at least 15min. Finally, voxelwise analysis revealed that the pre/post-task differences were also observed in several other brain regions, including the auditory cortex, visual areas, and the thalamus. Our data suggest that the recent performance of the simple button press task can result in elevated fcMRI CC and AF in relevant brain networks and that fcMRI scan should be performed either before evoked fMRI or after a sufficient time gap following fMRI.
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Molecular Epidemiology of Measles Virus in Taiwan in 2010-2011: the Common Genotype Changed from H1 to D9 and the First Appearance of D4
Journal of Medical Virology.
Jun, 2013 |
Pubmed ID: 23588738 Measles has been controlled effectively in some countries because of high coverage rates with an effective vaccine. However, measles outbreaks still occasionally occur in areas with high vaccine coverage as a result of imported transmission. To identify the sources of measles infection and to determine whether measles cases are part of a single outbreak or due to multiple importations, measles virus (MV) genotyping is required and plays an important role in MV elimination. In Taiwan, genotype H1 of MV was detected most frequently before 2009. From 2006 to 2011, 47 of 48 genotype H1 cases were associated with the imported cases, indicating that genotype H1 was not an endemic genotype in Taiwan after 2006. The distribution of the other genotypes (D3, D4, D5, D8, D9, and G3) detected during 2006-2011 varied by year. Taiwan has a pattern of measles genotypes that is consistent with the elimination of MV and with the absence of endemic genotypes. In this study, the genotypes of 40 cases of MV detected during 2010-2011 were investigated and analyzed. In 2010, the most common genotype changed from H1 (3/40) to D9 (35/40). In 2011, genotype H1 was not detected, and genotype D4 first appeared and was imported from Europe. The dynamic change of detected genotypes of MV in Taiwan is influenced by the activity of a measles control program in WHO regions. This study emphasizes that global synchronous elimination is important for an individual country or area to maintain free from MV.
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The Clinical Investigation of Disparity of Nonalcoholic Fatty Liver Disease in a Chinese Occupational Population in Taipei, Taiwan: Experience at a Teaching Hospital
Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health.
Apr, 2013 |
Pubmed ID: 23596266 The authors sought to explore the prevalence and factors related to nonalcoholic fatty liver disease (NAFLD) among occupational population in Taipei, Taiwan. A total of 8347 healthy adults voluntarily admitted to annual physical check-up. Blood samples and ultrasound-proved fatty liver sonography results were collected. The results showed that the prevalence of NAFLD was 48.4% and revealed a statistically significant increase with increasing population age. Males exhibited a greater prevalence of NAFLD than did females (57.8% vs 32.4%, P < .001). Using multiple logistic regression analysis, in addition to male gender, older age, higher body mass index, higher aspartate aminotransferase level, higher alanine aminotransferase level, presence of hypertension, presence of hyperuricemia, presence of hypercholesterolemia, higher fasting plasma glucose, and presence of hypertriglyceridemia were the significant factors associated with NAFLD. The differences in occupational professions were revealed. In conclusion, occupational populations are asymptomatic, and the diagnosis of NAFLD should be considered with older age, hyperuricemia, higher aspartate aminotransferase level, higher alanine aminotransferase level, and metabolic risk factors.
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Dealing with the Unexpected: Consumer Responses to Direct-access BRCA Mutation Testing
PeerJ.
2013 |
Pubmed ID: 23638402 Background. Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. Benefits and risks of providing this information directly to consumers are unknown. Methods. To assess and quantify emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service(®) report of three BRCA mutations that are common in Ashkenazi Jews, we invited all 136 BRCA1 and BRCA2 mutation-positive individuals in the 23andMe customer database who had chosen to view their BRCA reports to participate in this IRB-approved study. We also invited 160 mutation-negative customers who were matched for age, sex and ancestry. Semi-structured phone interviews were completed for 32 mutation carriers, 16 women and 16 men, and 31 non-carriers. Questions addressed personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of the result, emotional responses, perception of personal cancer risk, information sharing, and actions taken or planned. Results. Eleven women and 14 men had received the unexpected result that they are carriers of a BRCA1 185delAG or 5382insC, or BRCA2 6174delT mutation. None of them reported extreme anxiety and four experienced moderate anxiety that was transitory. Remarkably, five women and six men described their response as neutral. Most carrier women sought medical advice and four underwent risk-reducing procedures after confirmatory mutation testing. Male carriers realized that their test results implied genetic risk for female relatives, and several of them felt considerably burdened by this fact. Sharing mutation information with family members led to screening of at least 30 relatives and identification of 13 additional carriers. Non-carriers did not report inappropriate actions, such as foregoing cancer screening. All but one of the 32 mutation-positive participants appreciated learning their BRCA mutation status. Conclusions. Direct access to BRCA mutation tests, considered a model for high-risk actionable genetic tests of proven clinical utility, provided clear benefits to participants. The unexpected information demonstrated a cascade effect as relatives of newly identified carriers also sought testing and more mutation carriers were identified. Given the absence of evidence for serious emotional distress or inappropriate actions in this subset of mutation-positive customers who agreed to be interviewed for this study, broader screening of Ashkenazi Jewish women for these three BRCA mutations should be considered.
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Activation of Asparaginyl Endopeptidase Leads to Tau Hyperphosphorylation in Alzheimer's Disease
The Journal of Biological Chemistry.
May, 2013 |
Pubmed ID: 23640887 Neurofibrillary pathology of abnormally hyperphosphorylated tau is a key lesion of Alzheimer's disease and other tauopathies and its density in the brain directly correlates with dementia. The phosphorylation of tau is regulated by protein phosphatase -2A, which in turn is regulated by inhibitor-2, I2(PP2A). In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at N175 into N-terminal fragment (I2NTF) and C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase-2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated tau in Alzheimer's disease brain. Asparaginyl endopeptidase from Alzheimer's disease brain could cleave GST-I2(PP2A) except when I2(PP2A) was mutated at the cleavage site N 175 to Q. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase-2A, and hyperphosphorylation of tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer's disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase-2A-tau hyperphosphorylation pathway as a therapeutic target.
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Active Component of Danshen (Salvia Miltiorrhiza Bunge), Tanshinone I, Attenuates Lung Tumorigenesis Via Inhibitions of VEGF, Cyclin A, and Cyclin B Expressions
Evidence-based Complementary and Alternative Medicine : ECAM.
2013 |
Pubmed ID: 23662128 Tanshinone I (T1) and tanshinone II (T2) are the major diterpenes isolated from Danshen (Salvia miltiorrhiza Bunge). Three human lung adenocarcinoma cell lines, A549, CL1-0, and CL1-5, were treated with T1 and T2 for the in vitro antitumor test. Results showed that T1 was more effective than T2 in inhibiting the growth of lung cancer cells via suppressing the expression of VEGF, Cyclin A, and Cyclin B proteins in a dose-dependent manner. Moreover, a transgenic mice model of the human vascular endothelial growth factor-A165 (hVEGF-A 165) gene-induced pulmonary tumor was further treated with T1 for the in vivo lung cancer therapy test. T1 significantly attenuated hVEGF-A165 overexpression to normal levels of the transgenic mice (Tg) that were pretreated with human monocytic leukemia THP-1 cell-derived conditioned medium (CM). It also suppressed the formation of lung adenocarcinoma tumors (16.7%) compared with two placebo groups (50% for Tg/Placebo and 83.3% for Tg/CM/Placebo; P < 0.01). This antitumor effect is likely to slow the progression of cells through the S and G2/M phases of the cell cycle. Blocking of the tumor-activated cell cycle pathway may be a critical mechanism for the observed antitumorigenic effects of T1 treatment on vasculogenesis and angiogenesis.
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Identification and Significance of Naegleria Fowleri Isolated from the Hot Spring Which Related to the First Primary Amebic Meningoencephalitis (PAM) Patient in Taiwan
International Journal for Parasitology.
May, 2013 |
Pubmed ID: 23665128 Naegleria fowleri can cause primary amoebic meningoencephalitis, a rapidly developing and highly lethal infectious disease. The first confirmed case of primary amoebic meningoencephalitis in Taiwan was reported in November 2011, in which the patient visited a thermal spring recreational area 1week prior to hospitalisation. Water sampling was performed to verify the presence of Naegleria at the facility. According to our results, 32% and 20% of recreational water samples were contaminated with Naegleria spp. and Acanthamoeba spp., respectively. The genotypes of Naegleria identified at the hot spring included N. fowleri, Naegleria australiensis and Naegleria lovaniensis. Using PCR, it was determined that the strain of N. fowleri in one sample possessed the same genotype 2 as the clinical isolate. Thus, the thermal spring was suggested to be the likely source of infection. This is the first known instance of simultaneously isolating N. fowleri from both a patient as well as from a hot spring in Taiwan. Following this initial study, the pools at the thermal spring recreational area were drained, scrubbed and disinfected, and a follow-up study was performed 1month later. Naegleria fowleri was not detected in follow-up testing; however, other Naegleria spp. were identified. We postulate that the biofilm in the waterlines may have provided a reservoir for free-living amoebae. The presence/absence of Acanthamoeba and Naegleria spp. did not differ significantly with any measured parameters related to water quality; however, a high percentage of the thermal water pool samples were contaminated with Naegleria or Acanthamoeba. Thus, amoebic contamination may present a serious threat to the health of humans who engage in leisure activities at thermal springs.
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Creating Smoke-Free Places Through the UN Convention on the Rights of Persons With Disabilities
American Journal of Public Health.
May, 2013 |
Pubmed ID: 23678896 In some high-, middle-, and low-income countries, law has been employed to limit individuals' secondhand smoke exposure. Innovative legal tools are still needed, especially in low- and middle-income countries where smoking prevalence continues to rise. For some persons with severe respiratory conditions, the presence of secondhand smoke is intolerable and prevents their entrance into restaurants and other venues. With its adoption of the Convention on the Rights of Persons with Disabilities (CRPD) in 2006, the United Nations gave countries a new way to promote the rights of disabled individuals and simultaneously address secondhand smoke exposure. We analyze the CRPD's potential to advance tobacco control goals and offer recommendations for advocates, policymakers, and others seeking to apply this approach. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e6. doi:10.2105/AJPH.2012.301174).
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Molecular Characterization of a H5N1 Highly Pathogenic Avian Influenza Virus Clade 2.3.2.1b Circulating in Vietnam in 2011
Veterinary Microbiology.
Apr, 2013 |
Pubmed ID: 23683998 The emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses and the risk of a human pandemic have highlighted the need for advance stockpiling of vaccine. Current vaccines may be sub-optimally matched to the actual pandemic virus due to the rapid dissemination and ongoing evolution of avian H5N1 viruses. We report here the evaluation of efficacy of NIBRG-14 vaccine (clade 1 A/Vietnam/1194/2004) against the H5N1 HPAI virus strains circulating in Vietnam. The birds were either vaccinated with a single or booster dose of vaccine by subcutaneous injection; then challenged with three H5N1 HPAI viruses (clade 1, clade 2.3.2.1a and clade 2.3.2.1b) at day 21 post-vaccination (p. v.). The results showed that NIBRG-14 vaccine protected birds from clade 1 and clade 2.3.2.1a infections. Notably, we observed that NIGRG-14 vaccine did not confer protection against clade 2.3.2.1b challenge virus. To get new insights of how H5N1 clade 2.3.2.1b (A/Duck/QuangNgai/1037/11) virus can escape from the host immune response induced by the vaccine, we further analyzed the HA gene - a key virulence determinant of the virus. Amino acid sequence analysis indicated that this virus contained the sequence SPQRERRRK-R/G at the cleavage site in the HA molecule, indicating its high virulence. Additionally, we identified numerous mutations with amino acid substitutions in the hemagglutinin: M226I, I239S located at N-link glycosylation site and 2H, 45N, 53K 120D, 133A and 14N mutations at antigenic site, which can affect receptor specificity as well as viral pathogenicity. Notably, I239S and S133A mutations are unique to A/Duck/QuangNgai/1037/2011, suggesting that it may involve in the virus' ability to evade the host immune system. Taken together, phylogenetic analysis showed that continual mutations in the HA gene may have generated a novel antigenic strain and that probably changed the virulence of the virus and made the H5N1 clade 2.3.2.1b resistant to NIBRG-14 vaccine.
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Social Environmental Effects on Gene Regulation
Cellular and Molecular Life Sciences : CMLS.
May, 2013 |
Pubmed ID: 23685902 Social environmental conditions, particularly the experience of social adversity, have long been connected with health and mortality in humans and other social mammals. Efforts to identify the physiological basis for these effects have historically focused on their neurological, endocrinological, and immunological consequences. Recently, this search has been extended to understanding the role of gene regulation in sensing, mediating, and determining susceptibility to social environmental variation. Studies in laboratory rodents, captive primates, and human populations have revealed correlations between social conditions and the regulation of a large number of genes, some of which are likely causal. Gene expression responses to the social environment are, in turn, mediated by a set of underlying regulatory mechanisms, of which epigenetic marks are the best studied to date. Importantly, a number of genes involved in the response to the social environment are also associated with susceptibility to other external stressors, as well as certain diseases. Hence, gene regulatory studies are a promising avenue for understanding, and potentially developing strategies to address, the effects of social adversity on health.
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The Osmopressor Response Is Linked to Upregulation of Aquaporin-1 Tyrosine Phosphorylation on Red Blood Cell Membranes
Hypertension.
May, 2013 |
Pubmed ID: 23690341 Studies in patients with an impaired efferent baroreflex led us to discover that ingesting water induces a robust increase in blood pressure and vascular resistance. This response was also present in healthy subjects with intact baroreflexes, described as osmopressor response. This study was to discover the physiology of the osmopressor response by determining functional activation of the aquaporin-1 water channel receptor on red blood cell membranes in young healthy subjects. In a randomized, controlled, crossover fashion, 22 young healthy subjects (age, 19-27 years) ingested either 500 or 50 mL of water. Heart rate, blood pressure, cardiac index, and total peripheral vascular resistance were measured using a Finometer hemodynamic monitor. Blood sampling was performed at 5 minutes before and at 25 and 50 minutes after either the water ingestion or control session. Immunoblotting for aquaporin-1 tyrosine phosphorylation was performed before and after subjects ingested either 500 or 50 mL of water. At 25 minutes after the ingestion of 500 mL of water, total peripheral resistance increased significantly, and plasma osmolality decreased. Functional expression of aquaporin-1 tyrosine phosphorylation on red blood cell membranes increased significantly at 25 and 50 minutes after subjects ingested 500 mL of water compared with that before water ingestion. This study concludes that water ingestion produces upregulation of aquaporin-1 tyrosine phosphorylation on red blood cell, which presents as a novel biological marker that occurs simultaneously with the osmopressor response.
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Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice
Journal of Virology.
May, 2013 |
Pubmed ID: 23720717 Herpes simplex virus 1 (HSV-1) replication initiates inflammation and angiogenesis responses in the cornea to result in herpetic stromal keratitis (HSK), which is a leading cause of infection-induced vision impairment. Chemokines are secreted to modulate HSK by recruiting leukocytes which affect viral growth and by influencing angiogenesis. The present study used a murine infection model to investigate the significance of the chemokine, CXC chemokine ligand 10 (CXCL10; gamma interferon-inducible protein10 [IP-10]), in HSK. Here we show that HSV-1 infection of the cornea induced CXCL10 protein expression in epithelial cells. The corneas of mice with a targeted disruption of the gene encoding CXCL10 displayed decreases in levels of neutrophil-attracting cytokine (interleukin-6), primary neutrophil influx, and viral clearance 2 or 3 days post-infection. Subsequently, absence of CXCL10 aggravated HSK with elevated levels of interleukin-6, chemokines for CD4(+) T cells and/or neutrophils (macrophage inflammatory protein-1α and macrophage inflammatory protein-2), angiogenic factor (vascular endothelial growth factor A), secondary neutrophil influx, as well as infiltration of CD4(+) T cells to exacerbate opacity and angiogenesis in the cornea 14 or/to 28 days post-infection. Our results collectively show that endogenous CXCL10 contributes to recruit the primary neutrophil influx, affect the expression of cytokines, chemokines, and angiogenic factors, as well as reduce the viral titer and HSK severity.
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Identification and Structural Elucidation of in Vitro Metabolites of Atazanavir by HPLC and Tandem Mass Spectrometry
Journal of Mass Spectrometry : JMS.
Jun, 2013 |
Pubmed ID: 23722954 Atazanavir (marketed as Reyataz®) is an important member of the human immunodeficiency virus protease inhibitor class. LC-UV-MS(n) experiments were designed to identify metabolites of atazanavir after incubations in human hepatocytes. Five major (M1-M5) and seven minor (M7-M12) metabolites were identified. The most abundant metabolite, M1, was formed by a mono-oxidation on the t-butyl group at the non-prime side. The second most abundant metabolite, M2, was also a mono-oxidation product, which has not yet been definitively identified. Metabolites, M3 and M4, were structural isomers, which were apparently formed by oxidative carbamate hydrolysis. The structure of M5 comprises the non-prime side of atazanavir which contains a pyridinyl-benzyl group. Metabolite M6a was formed by the cleavage of the pyridinyl-benzyl side chain, as evidenced by the formation of the corresponding metabolic product, the pyridinyl-benzoic acid (M6b). Mono-oxidation also occurred on the pyridinyl-benzyl group to produce the low abundance metabolite M8. Oxidation of the terminal methyl groups produced M9 and M10, respectively, which have low chemical stability. Trace-level metabolites of di-oxidations, M11 and M12, were also detected, but the complexity of the molecule precluded identification of the second oxidation site. To our knowledge, metabolites M6b and M8 have not been reported. Copyright © 2013 John Wiley & Sons, Ltd.
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Selective Overexpression of Human SIRT1 in Adipose Tissue Enhances Energy Homeostasis and Prevents the Deterioration of Insulin Sensitivity with Ageing in Mice
American Journal of Translational Research.
2013 |
Pubmed ID: 23724165 SIRT1, a longevity regulator and NAD(+)-dependent deacetylase, plays a critical role in promoting metabolic fitness associated with calorie restriction and healthy ageing. Using a tissue-specific transgenic approach, the present study demonstrates that over-expression of human SIRT1 selectively in adipose tissue of mice prevents ageing-induced deterioration of insulin sensitivity and ectopic lipid distribution, reduces whole body fat mass and enhances locomotor activity. During ageing, the water-soluble vitamin biotin is progressively accumulated in adipose tissue. Over-expression of SIRT1 alleviates ageing-associated biotin accumulation and reduces the amount of biotinylated proteins, including acetyl CoA carboxylase, a major reservoir of biotin in adipose tissues. Chronic biotin supplementation increases adipose biotin contents and abolishes adipose SIRT1-mediated beneficial effects on insulin sensitivity, lipid metabolism and locomotor activity. Biochemical, spectrometric and chromatographic analysis revealed that biotin and its metabolites act as competitive inhibitors of SIRT1-mediated deacetylation. In summary, these results demonstrate that adipose SIRT1 is a key player in maintaining systemic energy homeostasis and insulin sensitivity; enhancing its activity solely in adipose tissue can prevent ageing-associated metabolic disorders.
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Role of Serum Dehydroepiandrosterone Sulfate Level on the Clearance of Chronic Hepatitis B Virus Infection
Journal of Gastroenterology.
Jun, 2013 |
Pubmed ID: 23728318 BACKGROUND: The natural course of chronic hepatitis B virus (HBV) infection and relevant host factors remain unclear. This study aims to investigate the impact of dehydroepiandrosterone sulfate (DHEAS) on the clearance of chronic HBV infection. METHODS: Two hundred and one hepatitis B e antigen (HBeAg)-positive chronic HBV-infected children (101 females) were recruited. Serum DHEAS levels were determined in all subjects at 15 years of age. Serum alanine aminotransferase (ALT) levels, DHEAS levels, HBV seromarkers, genotypes, and viral loads were included for analysis. RESULTS: Subjects with serum DHEAS levels >3.6 μmol/L at midpuberty had earlier HBeAg seroconversion (median age, 14.7 vs. 18.2 years; HR, 1.9; P = 0.03), and the impact persisted even after adjusting for gender, HBV genotype, peak ALT levels, and viral load. Subjects with DHEAS levels >3.6 μmol/L at 15 years of age had more HBV viral titers decrement from 15 to 20 years of age (mean ± SD, 3.5 ± 2.5 vs. 1.2 ± 2.2 log10 copies/mL; P = 0.05) and shorter duration for HBeAg seroconversion than others (mean ± SD, 5.6 ± 4.4 vs. 9.2 ± 4.9 years; P = 0.02). Higher serum DHEAS levels at 15 years of age are also associated with greater hepatitis B surface antigen (HBsAg) titer decrement from 15 to 20 years of age (correlation coefficient = 0.45, P = 0.04). CONCLUSIONS: Higher serum DHEAS levels at midpuberty predicts more HBV viral load and HBsAg titer decrement from midpuberty to young adulthood. Higher serum DHEAS levels at midpuberty also correlate with younger age of spontaneous HBeAg seroconversion in chronic genotype B and C HBV-infected patients.
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Modified Fabry-Perot Interferometer for Displacement Measurement in Ultra Large Measuring Range
The Review of Scientific Instruments.
May, 2013 |
Pubmed ID: 23742530 Laser interferometers have demonstrated outstanding measuring performances for high precision positioning or dimensional measurements in the precision industry, especially in the length measurement. Due to the non-common-optical-path structure, appreciable measurement errors can be easily induced under ordinary measurement conditions. That will lead to the limitation and inconvenience for in situ industrial applications. To minimize the environmental and mechanical effects, a new interferometric displacement measuring system with the common-optical-path structure and the resistance to tilt-angle is proposed. With the integration of optomechatronic modules in the novel interferometric system, the resolution up to picometer order, high precision, and ultra large measuring range have been realized. For the signal stabilization of displacement measurement, an automatic gain control module has been proposed. A self-developed interpolation model has been employed for enhancing the resolution. The novel interferometer can hold the advantage of high resolution and large measuring range simultaneously. By the experimental verifications, it has been proven that the actual resolution of 2.5 nm can be achieved in the measuring range of 500 mm. According to the comparison experiments, the maximal standard deviation of the difference between the self-developed Fabry-Perot interferometer and the reference commercial Michelson interferometer is 0.146 μm in the traveling range of 500 mm. With the prominent measuring characteristics, this should be the largest dynamic measurement range of a Fabry-Perot interferometer up till now.
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Healthcare Utilization and Expenditure Analysis Between Individuals with Intellectual Disabilities and the General Population in Taiwan: A Population-based Nationwide Child and Adolescent Study
Research in Developmental Disabilities.
Jun, 2013 |
Pubmed ID: 23751294 This study examines differences in outpatient-visit frequency and medical expenditures between (1) children and adolescents in Taiwan with intellectual disabilities and (2) children and adolescents in Taiwan's general population. A cross-sectional study was conducted to analyze data from 2007 provided by Taiwan's National Health Insurance program. A total of 236,045 beneficiaries younger than 19 years made use of outpatient services; among them, 35,802 had a principal diagnosis of mental retardation (intellectual disability). The average number of ambulatory visits was 14.9±12.4, which is much higher than in the United States and other developed countries. The mean number of annual visits of the individuals with intellectual disabilities was significantly higher than that of the general population in Taiwan (20.1±20.0 vs. 14.0±12.2); age, gender, urbanization level of residential area, and copayment status affected outpatient visit frequency. The mean annual outpatient costs were NTD6371.3±NTD11989.1 for the general population and NTD19724.9±NTD40469.9 for those with intellectual disabilities (US $1 equals approximately NTD30). Age, gender, urbanization level of residential area, and copayment status were the determinants that accounted for this difference in cost. Children and adolescents with intellectual disabilities had higher use rates of rehabilitative and psychiatric services than the general population. We conclude that individuals with intellectual disabilities had higher demands than the general population for healthcare services, especially for rehabilitative and psychiatric services.
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Program Specificity for Ptf1a in Pancreas Versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility
Molecular and Cellular Biology.
Jun, 2013 |
Pubmed ID: 23754747 The lineage-specific basic-helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 co-localize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA-binding of Ptf1a, and identify Fox and Sox gene families as part of this process.
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