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Sample records for photosensitization-induced early stages

  1. Early stage colon cancer.

    PubMed

    Freeman, Hugh James

    2013-12-14

    Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care.

  2. Early Life Stages

    EPA Pesticide Factsheets

    Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

  3. Dislocation generation during early stage sintering.

    NASA Technical Reports Server (NTRS)

    Sheehan, J. E.; Lenel, F. V.; Ansell, G. S.

    1973-01-01

    Discussion of the effects of capillarity-induced stresses on dislocations during early stage sintering. A special version of Hirth's (1963) theoretical calculation procedures modified to describe dislocation nucleation on planes meeting the sintering body's neck surface obliquely is shown to predict plastic flow at stress levels know to exist between micron size metal particles in the early stages of sintering.

  4. The Early Stages of Interlanguage.

    ERIC Educational Resources Information Center

    Schumann, John

    The stages of interlanguage, the speech of beginning second language learners as they progress toward second language fluency, are described. Examples are drawn from the speech of Spanish speaking students of English as a second language. The continuum of interlanguage development from native language forms to target language forms includes three…

  5. Liquid biopsy in early stage lung cancer

    PubMed Central

    Pérez-Ramírez, Cristina; Robles, Ana I.; Molina, Miguel Ángel; Faus-Dáder, María José; Calleja-Hernández, Miguel Ángel

    2016-01-01

    Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). However, 30% to 80% of these patients will die within 5 yearS of diagnosis. Circulating cell-free DNA (cfDNA) harbors pathologic characteristics of the original tumor, such as gene mutations or epigenetic alterations. Analysis of cfDNA has revolutionized the clinical care of advanced lung cancer patients undergoing targeted therapies. However, the low concentration of cfDNA in the blood of early-stage NSCLC patients has hampered its use for management of early disease. Continuing development of more specific and sensitive techniques for detection and analysis of cfDNA will soon enable its leverage in early stage and, perhaps, even screening settings. Therefore, cfDNA analysis may become a tool used for routine NSCLC diagnosis and for monitoring tumor burden, as well as for identifying hidden residual disease. In this review, we will focus on the current evidence of cfDNA in patients with early-stage NSCLC, new and upcoming approaches to identify circulating-tumor biomarkers, their clinical applications and future directions. PMID:27826533

  6. Treatment of early stage vocal cord carcinoma

    SciTech Connect

    Ayers, G.

    1989-03-01

    The cure rates for early stage vocal cord cancer are excellent with primary radiotherapy. Voice quality remains as good or becomes better than prior to treatment. For the local failures that do occur, surgical salvage will yield ultimate cure rates of about 95% for T1 and 90% for T2 tumors.

  7. Suicide in the Early Stage of Schizophrenia.

    PubMed

    Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

    2016-01-01

    Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects with subthreshold psychotic experiences. Factors associated with the risk of suicide in the early phase of schizophrenia are previous suicidal attempts and social aspects: the lack of social support and stable relationships, social drift after the first episode, and social impairment. Also, several psychotic symptoms (suspiciousness, paranoid delusions, mental disintegration and agitation, negative symptoms, depression and hopelessness, and command hallucinations) and substance abuse are associated with higher risk of suicide. It has been described that perfectionism and good levels of insight among individuals who have recently developed psychotic symptoms are significantly associated with higher numbers of suicidal attempts. Moreover, recent evidences show that prefrontal cortex-based circuit dysfunction may be related to suicide in the early stage of schizophrenia. This narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed.

  8. Suicide in the Early Stage of Schizophrenia

    PubMed Central

    Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

    2016-01-01

    Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects with subthreshold psychotic experiences. Factors associated with the risk of suicide in the early phase of schizophrenia are previous suicidal attempts and social aspects: the lack of social support and stable relationships, social drift after the first episode, and social impairment. Also, several psychotic symptoms (suspiciousness, paranoid delusions, mental disintegration and agitation, negative symptoms, depression and hopelessness, and command hallucinations) and substance abuse are associated with higher risk of suicide. It has been described that perfectionism and good levels of insight among individuals who have recently developed psychotic symptoms are significantly associated with higher numbers of suicidal attempts. Moreover, recent evidences show that prefrontal cortex-based circuit dysfunction may be related to suicide in the early stage of schizophrenia. This narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed. PMID:27445872

  9. An actuarial approach to comparing early stage and late stage lung cancer mortality and survival.

    PubMed

    Goldberg, Sara W; Mulshine, James L; Hagstrom, Dale; Pyenson, Bruce S

    2010-02-01

    Comparing the mortality characteristics of different cohorts is an essential process in the life insurance industry. Pseudodisease, lead-time bias, and length bias, which are critical to determining the value of cancer screening, have close analogues in life insurance company management, including the temporal impact of underwriting. Ratios of all-cause mortality rates for cancer cohorts relative to standard population mortality rates can provide insights into early stage and late stage mortality differences, differences by age, sex, race, and histology, and allow modeling of biases associated with early stage detection or screening protocols. The Surveillance, Epidemiology and End Results (SEER) data set has characteristics that allow efficient application of actuarial techniques. We show the mortality burden associated with treated early stage lung cancer and that identifying all lung cancers at early stage could reduce US lung cancer deaths by over 70,000 per year.

  10. Critical pneumonia complicating early-stage pregnancy.

    PubMed

    Mercieri, Marco; Di Rosa, Roberta; Pantosti, Annalisa; De Blasi, Roberto Alberto; Pinto, Giovanni; Arcioni, Roberto

    2010-03-01

    We present a case of community-acquired methicillin-resistant Staphylococcus aureus necrotizing pneumonia, Panton-Valentine leukocidin positive, in a woman at 14 weeks of pregnancy. To our knowledge, this is the first case reporting this critical lung infection occurring during an early phase of pregnancy. This case study alerts physicians to the increasing worldwide spread of these uncommon yet virulent and potentially lethal infections. In our patient, antibiotic therapy with linezolid plus rifampin started at 14 weeks of pregnancy had a successful outcome without inducing toxicity or teratogenesis in the fetus.

  11. Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

    PubMed

    Herst, J; Crump, M; Baldassarre, F G; MacEachern, J; Sussman, J; Hodgson, D; Cheung, M C

    2017-01-01

    In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: 'Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma'; 'The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival'. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients' point of view.

  12. Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

    PubMed

    Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

    2016-12-29

    The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH4/H2S/H2O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

  13. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  14. Radiation Plus Chemotherapy in Early-Stage Hodgkin Lymphoma

    Cancer.gov

    Adding radiation therapy to chemotherapy may improve outcomes in patients with early-stage Hodgkin lymphoma, according to a paper published in the Cochrane Database of Systematic Reviews in February 2011, but the long-term effects of this regimen are not

  15. Early Stages of the Evolution of Life: a Cybernetic Approach

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  16. [The conservative treatment of early-stage benign prostatic hypertrophy].

    PubMed

    Kumanov, Kh; Stoianova, V; Lilov, A; Kaloianov, D

    1993-01-01

    After outlining the methods currently used in benign prostate hyperplasia (BPH) treatment, data defining some etiological aspects of the disease are briefly analyzed. Initial experience had with the treatment of early stage BPH using Permixon--a drug exerting effect on alpha-2 reductase--is described. The results in a series of twenty-seven patients presenting BPH are encouraging.

  17. Signatures of unfolding in the early stages of protein denaturation

    NASA Astrophysics Data System (ADS)

    Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

    2012-04-01

    A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

  18. Bioaccumulation of lipophilic substances in fish early life stages

    SciTech Connect

    Petersen, G.I.; Kristensen, P.

    1998-07-01

    Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to those for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.

  19. Folding of Polymer Chains in Early Stage of Crystallization

    NASA Astrophysics Data System (ADS)

    Yuan, Shichen; Miyoshi, Toshikazu

    Understanding the structural formation of long polymer chains in the early stage of crystallization is one of the long-standing problems in polymer science. Using solid state NMR, we investigated chain trajectory of isotactic polypropylene in the mesomorphic nano-domains formed via rapid and deep quenching. Comparison of experimental and simulated 13C-13C Double Quantum (DQ) buildup curves demonstrated that instead of random re-entry models and solidification models, individual chains in the mesomorphic form iPP adopt adjacent reentry sequences with an average folding number of = 3-4 (assuming an adjacent re-entry fraction of of 100%) during mesomorphic formation process via nucleation and growth in the early stage. This work was financially supported by the National Science Foundation (Grant DMR-1105829 and 1408855) and startup funds from the UA.

  20. Maternal warming affects early life stages of an invasive thistle.

    PubMed

    Zhang, R; Gallagher, R S; Shea, K

    2012-09-01

    Maternal environment can influence plant offspring performance. Understanding maternal environmental effects will help to bridge a key gap in the knowledge of plant life cycles, and provide important insights for species' responses under climate change. Here we show that maternal warming significantly affected the early life stages of an invasive thistle, Carduus nutans. Seeds produced by plants grown in warmed conditions had higher germination percentages and shorter mean germination times than those produced by plants under ambient conditions; this difference was most evident at suboptimal germination temperatures. Subsequent seedling emergence was also faster with maternal warming, with no cost to seedling emergence percentage and seedling growth. Our results suggest that maternal warming may accelerate the life cycle of this species via enhanced early life-history stages. These maternal effects on offspring performance, together with the positive responses of the maternal generation, may exacerbate invasions of this species under climate change.

  1. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  2. Effects of genistein on early-stage cutaneous wound healing

    SciTech Connect

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  3. Early-stage Alzheimer disease represents increased suicidal risk in relation to later stages.

    PubMed

    Lim, Wee Shiong; Rubin, Eugene H; Coats, Mary; Morris, John C

    2005-01-01

    The level of risk for suicide in individuals with Alzheimer disease (AD) generally is considered to be low. It is important to recognize, however, that suicide can occur in early-stage Alzheimer disease on the background of a distinct high-risk profile. The objective of this report is to describe the clinical profiles of individuals with very mild Alzheimer disease who either attempted or completed suicide. We describe two participants in a longitudinal study of early-stage Alzheimer disease who were in the ninth decade of life and had very mild Alzheimer disease. Consistent with earlier cases reported in the literature, both displayed the following high-risk phenotype predisposing to suicidal risk: male gender, highly educated professional, preserved insight, dysthymic symptoms that did not meet criteria for major depression and post-dated the onset of cognitive decline, and suicidal ideation. Neuropathological examination confirmed histologic Alzheimer disease in both cases. These cases, taken together, emphasize the need for awareness that early-stage Alzheimer disease may present a unique suicidal risk compared with later stages.

  4. Acoustic determination of early stages of intravascular blood coagulation.

    PubMed

    Uzlova, Svetlana G; Guria, Konstantin G; Guria, Georgy Th

    2008-10-13

    The blood coagulation system (BCS) is a complex biological system playing a principal role in the maintenance of haemostasis. Insufficient activity of the BCS may lead to bleeding and blood loss (e.g. in the case of haemophilia). On the other hand, excessive activity may cause intravascular blood coagulation, thromboses and embolization. Most of the methods currently used for BCS monitoring suffer from the major disadvantage of being invasive. The purpose of the present work is to demonstrate the feasibility of using ultrasonic methods for non-invasive registration of the early stages of blood coagulation processes in intensive flows. With this purpose, a special experimental set-up was designed, facilitating the simultaneous detection of optical and acoustic signals during the clotting process. It was shown that (i) as microemboli appear in the flow during the early stage of blood coagulation, the intensity of the Doppler signal increases twofold, and (ii) microemboli formation in the early stages of blood clotting always reveals itself through an acoustic contrast. Both of these effects are well defined, so we hope that they may be used for non-invasive BCS monitoring in clinical practice.

  5. Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health.

    PubMed

    Ahmed, Usman; Anwar, Attia; Savage, Richard S; Costa, Matthew L; Mackay, Nicola; Filer, Andrew; Raza, Karim; Watts, Richard A; Winyard, Paul G; Tarr, Joanna; Haigh, Richard C; Thornalley, Paul J; Rabbani, Naila

    2015-03-19

    There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity.

  6. High-throughput quantification of early stages of phagocytosis.

    PubMed

    Yeo, Jeremy Changyu; Wall, Adam Alexander; Stow, Jennifer Lea; Hamilton, Nicholas Ahti

    2013-09-01

    Phagocytosis--the engulfment of cells and foreign bodies--is an important cellular process in innate immunity, development, and disease. Quantification of various stages of phagocytosis, especially in a rapid screening fashion, is an invaluable tool for elucidating protein function during this process. However, current methods for assessing phagocytosis are largely limited to flow cytometry and manual image-based assays, providing limited information. Here, we present an image-based, semi-automated phagocytosis assay to rapidly quantitate three distinct stages during the early engulfment of opsonized beads. Captured images are analyzed using the image-processing software ImageJ and quantified using a macro. Modifications to this method allowed quantification of phagocytosis only in fluorescently labeled transfected cells. Additionally, the time course of bead internalization could be measured using this approach. The assay could discriminate perturbations to stages of phagocytosis induced by known pharmacological inhibitors of filamentous actin and phosphoinositol-3-kinase. Our methodology offers the ability to automatically categorize large amounts of image data into the three early stages of phagocytosis within minutes, clearly demonstrating its potential value in investigating aberrant phagocytosis when manipulating proteins of interest in drug screens and disease.

  7. Involvement of 15-lipoxygenase in early stages of atherogenesis

    PubMed Central

    1994-01-01

    The arachidonate 15-lipoxygenase which is expressed in atherosclerotic lesions is implicated in the oxidative modification of low density lipoproteins during atherogenesis. To obtain experimental in vivo evidence for this hypothesis, we analyzed the structure of oxygenated lipids isolated from the aorta of rabbits fed with a cholesterol-rich diet for different time periods and compared the pattern of oxygenation products with that isolated from low density lipoproteins treated in vitro with the pure rabbit 15-lipoxygenase and with oxygenated lipids isolated from advanced human atherosclerotic lesions. In early atherosclerotic lesions (12-wk cholesterol feeding), specific lipoxygenase products were detected whose structure was similar to those isolated from lipoxygenase-treated low density lipoproteins. The appearance of these products did coincide with the lipid deposition in the vessel wall. In later stages of atherogenesis (26-wk cholesterol feeding) the degree of oxidative modification of the tissue lipids did increase but the share of specific lipoxygenase products was significantly lower, suggesting an increasing overlay of the specific lipoxygenase products by nonenzymatic lipid peroxidation. In advanced human atherosclerotic lesions, large amounts of oxygenation products were detected whose structure suggests a nonenzymatic origin. These data suggest that the arachidonate 15-lipoxygenase is of pathophysiological importance during the early stages of atherogenesis. In later stages of plaque development nonenzymatic lipid peroxidation becomes more relevant. PMID:8195716

  8. Early stages of irradiation induced dislocations in urania

    NASA Astrophysics Data System (ADS)

    Chartier, A.; Onofri, C.; Van Brutzel, L.; Sabathier, C.; Dorosh, O.; Jagielski, J.

    2016-10-01

    The early stages of nucleation and growth of dislocations by irradiation in urania is clarified based on the combination of experiments and atomistic calculations. It is established that irradiation induced dislocations follow a five stage process: (i) point defects are first created by irradiation, (ii) they aggregate into clusters, (iii) from which nucleate Frank loops, (iv) which transform into unfaulted loops via Shockley that in turn grow, and (v) finally reorganize into forest dislocations. Stages (i)-(iii) participate in the lattice expansion while the onset of lattice contraction starts with stage (iv), i.e., when unfaulted loops nucleate. Irradiation induced dislocations operate in the spontaneous recombination regime, to be opposed to the thermal diffusion regime. Body of arguments collaborates to this statement, the main one is the comparison between characteristic distances estimated from the dose rate (Vat/(K0×τ ) ) 1/3 and from the diffusion coefficient (D×τ ) 1/2 . Such a comparison identifies materials under irradiation as belonging either into the recombination regime or not.

  9. Effects of genistein on early-stage cutaneous wound healing.

    PubMed

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-κB and TNF-α expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing.

  10. Reproductive and early life stages pathology - Histopathology workshop report

    USGS Publications Warehouse

    Bruno, D.W.; Nowak, B.; Elliott, Diane G.

    2006-01-01

    Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

  11. Histopathological diagnosis of acral lentiginous melanoma in early stages.

    PubMed

    Fernandez-Flores, Angel; Cassarino, David S

    2017-02-01

    Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma.

  12. Late stages of accumulation and early evolution of the planets

    NASA Technical Reports Server (NTRS)

    Vityazev, Andrey V.; Perchernikova, G. V.

    1991-01-01

    Recently developed solutions of problems are discussed that were traditionally considered fundamental in classical solar system cosmogony: determination of planetary orbit distribution patterns, values for mean eccentricity and orbital inclinations of the planets, and rotation periods and rotation axis inclinations of the planets. Two important cosmochemical aspects of accumulation are examined: the time scale for gas loss from the terrestrial planet zone, and the composition of the planets in terms of isotope data. It was concluded that the early beginning of planet differentiation is a function of the heating of protoplanets during collisions with large (thousands of kilometers) bodies. Energetics, heat mass transfer processes, and characteristic time scales of these processes at the early stages of planet evolution are considered.

  13. Prognostic factors in early-stage ovarian cancer

    PubMed Central

    Tognon, Germana; Carnazza, Mario; Ragnoli, Monica; Calza, Stefano; Ferrari, Federico; Gambino, Angela; Zizioli, Valentina; Notaro, Sara; Sostegni, Benedetta; Sartori, Enrico

    2013-01-01

    The purpose of this study was to identify the main prognostic factors in patients with early-stage epithelial ovarian cancer. Data were extracted from 222 patients with initial stage (I–IIA) invasive epithelial ovarian cancer treated with primary surgery followed or not followed by adjuvant therapy, from 1 January 1980 to 31 December 2008, at the Division of Obstetrics and Gynecology, Spedali Civili, Brescia, Italy; the median follow-up was 79 months (SD ± 35,945, range 20–250 months). The negative prognostic factors that were statistically significant (p<0.050) in univariate analysis were grade 2, 3, and X (clear cell in our study); stage IB, IC, IIA; positive peritoneal cytology, age equal to/greater than 54; dense adhesions; capsule rupture (pre-operative or intra-operative) and endometrioid histotype (only for disease-free survival (DFS)). Positive cytology was strongly associated with peritoneal relapses, while adhesions were associated with pelvic relapses. A positive prognosis was associated with the mucinous histotype. Conservative treatment had been carried out in 52% of patients under 40 years of age, and we detected only two relapses and three completions of surgery after a few weeks among 31 women in total. Our study indicated a possible execution in patients with patients with cancer stage IA G1–G2 (p=0.030) or IC G1 (p=0.050), provided well staged. Adjuvant chemotherapy improved the survival of cancers that were not IA G1. The positive prognostic role of taxanes must be emphasised, when used in combination with platino. PMID:23781280

  14. Early stage of nanodroplet impact on solid wall

    NASA Astrophysics Data System (ADS)

    Kobayashi, Kazumichi; Konno, Kazuki; Yaguchi, Hisao; Fujii, Hiroyuki; Sanada, Toshiyuki; Watanabe, Masao

    2016-03-01

    In this study, we investigated nanodroplet spreading at the early stage after the impact using molecular dynamics simulations by changing the magnitude of the intermolecular force between the liquid and wall molecules. We showed that the droplet deformation after the impact greatly depends on the intermolecular force. The temporal evolution of the spreading diameters was measured by the cylindrical control volume for several molecular layers in the vicinity of the wall. At the early stage of the nanodroplet impact, the normalized spreading radius of the droplet is proportional to the square root of the normalized time, t ˆ . This result is understood by the geometrical consideration presented by Rioboo et al. ["Time evolution of liquid drop impact onto solid, dry surfaces," Exp. Fluids 33, 112-124 (2002)]. In addition, we found that as the intermolecular force between the liquid and wall becomes stronger, the normalized spreading diameter of the first molecular layer on the wall remains less dependent on the impact velocity. Furthermore, the time evolution of the droplet spreading changes from √{ t ˆ } to log t ˆ with time.

  15. Sensorimotor Cortical Neuroplasticity in the Early Stage of Bell's Palsy

    PubMed Central

    Dai, Minhui; Xuan, Lihua; Cao, Zhijian; Zhou, Sisi; Lang, Courtney; Lv, Kun

    2017-01-01

    Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brain's ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bell's palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations. PMID:28299208

  16. Early stages during plasma nitriding of pure iron

    SciTech Connect

    Palacios, M.D.; Martinez, O.; Oseguera, J.

    1995-12-31

    The sequence of nitride formation during the early stages of plasma nitriding of pure iron was studied by optical microscopy, SEM, TEM and x-ray diffraction. Plasma nitriding at {approximately}490 C in a 25 vol.%H{sub 2} + 75 vol.%N{sub 2} mixture starts with the formation of {gamma}{prime}-Fe{sub 4}N after 40s. Once {gamma}{prime} nucleates, it mainly spreads laterally due to diffusion shortcuts in the discontinuous surface nitride layer. Before {gamma}{prime} is continuous on the surface, {epsilon} nucleates on top of it shortly after 40S. Epsilon is then observed to grow, both inwardly and laterally along with {gamma}{prime}. A compact {gamma}{prime}/{epsilon} bilayer forms on the surface at around 100s. The kinetics of nucleation, growth and compactation of the nitrides observed in the present work was significantly more rapid than in any of the nitriding process reported in the literature, including plasma nitriding. The acceleration of the nitriding kinetics in the early stages of plasma nitriding may be attributed to enhanced diffusion resulting from a high nitrogen flux from the plasma atmosphere. The results presented are consistent with the findings of a companion work on modeling the kinetics of nitride layer growth.

  17. Understanding early-stage dune development: morphodynamics of aeolian protodunes

    NASA Astrophysics Data System (ADS)

    Baddock, Matthew; Wiggs, Giles; Nield, Joanna

    2016-04-01

    For such a fundamental aspect of bedform development, the initiation and early-stage growth of sand dunes remain poorly understood. Protodunes are bedforms within the continuum of early-stage depositional aeolian features that exist between flat sand patches and small dunes. As transitory bedforms with the potential to develop into dunes, the detailed study of protodune morphodynamics can provide significant insights into nascent dune development. As part of a multi-annual study investigating bedform change through repeat morphological surveys of bedforms with differing maturity, measurements of near-surface airflow and sand transport were conducted over a protodune in a small Namibian barchan dune field. The protodune was approximately 85 m in length and 1 m high, and was without a slipface. Data show that over the course of a week, patterns of airflow and transport flux variation were linked with accretion at the crest, and erosion of the leeside edge showing an increase in protodune height, and providing evidence of the dune's vertical development. Surveys reveal the longer term evolution of the protodune, in the context of changes exhibited by nearby, fully developed barchan dunes, and long term monitoring of wind regime at the site.

  18. Effects of hydroelectric turbine passage on fish early life stages

    SciTech Connect

    Cada, G.F.

    1991-01-01

    Turbine-passage mortality has been studied extensively for juveniles and adults of migratory fish species, but few studies have directly quantified mortality of fish eggs and larvae. An analysis of literature relating to component stresses of turbine passage (i.e., pressure changes, blade contact, and shear) indicates that mortality of early life stages of fish would be relatively low at low-head, bulb turbine installations. The shear forces and pressure regimes normally experienced are insufficient to cause high mortality rates. The probability of contact with turbine blades is related to the size of the fish; less than 5% of entrained ichthyoplankton would be killed by the blades in a bulb turbine. Other sources of mortality (e.g., cavitation and entrainment of fish acclimated to deep water) are controlled by operation of the facility and thus are mitigable. Because turbine-passage mortality among fish early life stages can be very difficult to estimate directly, it may be more fruitful to base the need for mitigation at any given site on detailed knowledge of turbine characteristics and the susceptibility of the fish community to entrainment. 7 refs., 1 fig.

  19. Early stage of Superradiance from Bose-Einstein condensates

    NASA Astrophysics Data System (ADS)

    Buchmann, Lukas

    2011-05-01

    We investigate the dynamics of matter and optical waves at the early stage of superradiant Rayleigh scattering from Bose-Einstein condensates, an instance of four-wave-mixing of matter and optical waves. Our analysis is within a spatially dependent model which treats the matter-waves as well as the optical end-fire modes quantum mechanically and is capable of providing analytic solutions for the operators of interest. In particular, we study the statistical properties of the outgoing scattered light which provide insight into the rich internal dynamics of the system at this early stage. Furthermore, we investigate coherence properties of pairs of counter propagating atomic sidemodes produced during the process. It is shown that these clouds exhibit long-range spatial coherence and strong nonclassical density cross-correlations due to entanglement between the clouds. These findings make this scheme a promising candidate for the production of highly directional nonclassically correlated atomic pulses. Our prediction of number difference squeezing between the clouds was observed in another instance of a four-wave mixing process using metastable helium. Work performed at IESL-FORTH in Crete, Greece

  20. Widespread tau seeding activity at early Braak stages.

    PubMed

    Furman, Jennifer L; Vaquer-Alicea, Jaime; White, Charles L; Cairns, Nigel J; Nelson, Peter T; Diamond, Marc I

    2017-01-01

    Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also develop seeding activity prior to accumulation of phospho-tau. We measured tau seeding activity across four brain regions (hippocampus, frontal lobe, parietal lobe, and cerebellum) in 104 fresh-frozen human AD brain samples from all Braak stages. We observed widespread seeding activity, notably in regions predicted to be free of phospho-tau deposition, and in detergent-insoluble fractions that lacked tau detectable by ELISA. Seeding activity correlated positively with Braak stage and negatively with MMSE. Our results are consistent with early transcellular propagation of tau seeds that triggers subsequent development of neuropathology. The FRET-based seeding assay may also complement standard neuropathological classification of tauopathies.

  1. 13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early Stage SBICs. (a) Reserve requirement. If you are an Early Stage SBIC with outstanding Leverage, for...

  2. 13 CFR 107.1180 - Required distributions to SBA by Early Stage SBICs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1180 Required distributions to SBA by Early Stage SBICs. (a) Distribution requirement. If you are an Early Stage SBIC with outstanding Leverage, you...

  3. 13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early Stage SBICs. (a) Reserve requirement. If you are an Early Stage SBIC with outstanding Leverage, for...

  4. 13 CFR 107.1180 - Required distributions to SBA by Early Stage SBICs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1180 Required distributions to SBA by Early Stage SBICs. (a) Distribution requirement. If you are an Early Stage SBIC with outstanding Leverage, you...

  5. Axial differentiation and early gastrulation stages of the pig embryo.

    PubMed

    Hassoun, Romia; Schwartz, Peter; Feistel, Kerstin; Blum, Martin; Viebahn, Christoph

    2009-12-01

    Differentiation of the principal body axes in the early vertebrate embryo is based on a specific blueprint of gene expression and a series of transient axial structures such as Hensen's node and the notochord of the late gastrulation phase. Prior to gastrulation, the anterior visceral endoderm (AVE) of the mouse egg-cylinder or the anterior marginal crescent (AMC) of the rabbit embryonic disc marks the anterior pole of the embryo. For phylogenetic and functional reasons both these entities are addressed here as the mammalian anterior pregastrulation differentiation (APD). However, mouse and rabbit show distinct structural differences in APD and the molecular blueprint, making the search of general rules for axial differentiation in mammals difficult. Therefore, the pig was analysed here as a further species with a mammotypical flat embryonic disc. Using light and electron microscopy and in situ hybridisation for three key genes involved in early development (sox17, nodal and brachyury), two axial structures of early gastrulation in the pig were identified: (1) the anterior hypoblast (AHB) characterised by increased cellular height and density and by sox17 expression, and (2) the early primitive streak characterised by a high pseudostratified epithelium with an almost continuous but unusually thick basement membrane, by localised epithelial-mesenchymal transition, and by brachyury expression in the epiblast. The stepwise appearance of these two axial structures was used to define three stages typical for mammals at the start of gastrulation. Intriguingly, the round shape and gradual posterior displacement of the APD in the pig appear to be species-specific (differing from all other mammals studied in detail to date) but correlate with ensuing specific primitive streak and extraembryonic mesoderm development. APD and, hence, the earliest axial structure presently known in the mammalian embryo may thus be functionally involved in shaping extraembryonic membranes and

  6. Research on the early planet formation stages with IPE

    NASA Astrophysics Data System (ADS)

    Ingo von Borstel, Olaf; Blum, Jurgen; Schraepler, Rainer

    The early stages of planet formation are characterized by growth of fractal aggregates, starting from (sub-)micrometer-sized grains to (fractal) aggregates of roughly mm size. In the last 20 years a number of experiments on the behaviour and growth mechanisms of aggregates has been carried out. Laboratory experiments are limited due to sedimentation (e.g. Heim and Blum 1998, Wurm et al 2001). Previous long-term microgravity experiments CODAG (Blum et al 2000) and CODAG-SRE (Krause and Blum 2004) were mainly limited by the diffusion of particles, a fact which IPE tries to overcome by means of a particle trap. We present how IPE will help to extend these experimental boundaries and how we plan to utilize IPE. Finally we outline the expectations on the facility from a planet formation point of view in the domain of the mutual interactions, evolution, growth and morphology of fractal aggregates.

  7. Contingency Table Browser − prediction of early stage protein structure

    PubMed Central

    Kalinowska, Barbara; Krzykalski, Artur; Roterman, Irena

    2015-01-01

    The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table − this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them − analysis of specific protein sequences from the point of view of their structural ambiguity. PMID:26664034

  8. Flame acceleration in the early stages of burning in tubes

    SciTech Connect

    Bychkov, Vitaly; Fru, Gordon; Petchenko, Arkady; Akkerman, V'yacheslav; Eriksson, Lars-Erik

    2007-09-15

    Acceleration of premixed laminar flames in the early stages of burning in long tubes is considered. The acceleration mechanism was suggested earlier by Clanet and Searby [Combust. Flame 105 (1996) 225]. Acceleration happens due to the initial ignition geometry at the tube axis when a flame develops to a finger-shaped front, with surface area growing exponentially in time. Flame surface area grows quite fast but only for a short time. The analytical theory of flame acceleration is developed, which determines the growth rate, the total acceleration time, and the maximal increase of the flame surface area. Direct numerical simulations of the process are performed for the complete set of combustion equations. The simulations results and the theory are in good agreement with the previous experiments. The numerical simulations also demonstrate flame deceleration, which follows acceleration, and the so-called ''tulip flames''. (author)

  9. Cell proliferation during the early stages of human eye development.

    PubMed

    Bozanić, Darka; Saraga-Babić, Mirna

    2004-08-01

    The distribution as well as the ultrastructural and biochemical characteristics of proliferating cells in the human eye were investigated in five conceptuses of 5-9 postovulatory weeks, using morphological techniques and Ki-67 immunostaining. The Ki-67 nuclear protein was used as a proliferation marker because of its expression in all phases of the cell cycle except the resting phase (G0). The labelling indices of Ki-67-positive cells were analysed by means of the Kruskal-Wallis ANOVA test and the Wilcoxon matched-pairs test. In the 5th week, mitotic cells were the most numerous between the two layers of the optic cup, the optic cup and stalk, and between the lens pit and the surface ectoderm. During the 6th week, cells were observed in the lens epithelium covering the whole cavity of the lens vesicle as well as in the neuroblast zone and the pigmented epithelium of the retina. At later stages (7th-9th weeks), Ki-67-positive cells were restricted to the anterior lens epithelium, the outer neuroblast zone, and the pigmented retina. Throughout all stages examined, mitotic figures were found lying exclusively adjacent to the intraretinal space. Early in the lens pit, they were confined to the free epithelial surface, and later were facing the cavity of the lens vesicle. The proliferative activity was the most intensive in the 6th week, whereas it decreased significantly in the later stages. Additionally, when proliferative activities were compared, the peripheral retina appeared to be less mature than the central before the 9th week. In the earliest analysed stage, cell proliferation might be associated with the sculpturing of the optic cup and stalk, the cornea, and the lens. In the 6th week, the most intensive proliferation seems to be involved not only in the further morphogenesis of the optic cup and the lens vesicle but also in the retinal neurogenesis. At later stages, the decreased proliferation might participate in the neurogenesis of the outer neuroblast zone

  10. Locomotor function in the early stage of Parkinson's disease.

    PubMed

    Carpinella, Ilaria; Crenna, Paolo; Calabrese, Elena; Rabuffetti, Marco; Mazzoleni, Paolo; Nemni, Raffaello; Ferrarin, Maurizio

    2007-12-01

    The cardinal motor symptoms of Parkinson's disease (PD) have been widely investigated with particular reference to abnormalities of steady-state walking. The great majority of studies, however are related to severe forms of PD patients (phases > = 3 of Hoehn and Yahr scale), where locomotor abnormalities are clearly manifested. Goal of the present study was to quantitatively describe locomotor symptoms in subjects with mild PD. Accordingly, a multitask protocol involving instrumental analysis of steady-state linear walking, initiation of gait, and turning while walking was applied to a group of patients with idiopathic PD in their early clinical stage (phases 1 and 2 of Hoehn and Yahr scale), as well as in age-matched elderly controls. Kinematic, kinetic, and myoelectric measures were obtained by optoelectronic motion analysis, force platform, and telemetric electromyography. Results in PD patients showed a tendency to bradykinetic gait, with reduction of walking speed and cadence. Impairments of gait initiation consisted in reduction of the backward shift of the center of pressure (CoP) and prolongation of the stepping phase. Alterations of the turning task were more consistent and included delayed reorientation of the head toward the new direction, altered head-upper trunk rotational strategy, and adoption of a greater number of steps to complete the turning. It is concluded that patients in the early stage of PD reveal mild alterations of steady-state linear walking and more significant anomalies in the transitional conditions, especially during changes in the travel direction. Quantitative analysis of nonstationary locomotor tasks might be a potentially useful starting point for further studies on the pathophysiology of PD.

  11. White matter development in the early stages of psychosis.

    PubMed

    Peters, Bart D; Karlsgodt, Katherine H

    2015-01-01

    Schizophrenia has been conceptualized as a disorder of both neurodevelopment and a disorder of connectivity. One important aspect of the neurodevelopmental hypothesis is that schizophrenia is no longer thought to have discrete illness time points, but rather a long trajectory of brain changes, spanning many years, across a series of stages of the disease including the prodrome, first episode, and chronic period. As the disease progresses, there is a complex relationship between age related changes and disease related changes. Therefore, neural changes, and specifically white matter based connectivity changes, in schizophrenia may be best conceptualized based on a lifespan trajectory. In this selective review, we discuss healthy changes in white matter integrity that occur with age, as well as changes that occur across illness stages. We further propose a set of models that might explain lifespan changes in white matter integrity in schizophrenia, with the conclusion that the evidence most strongly supports a pattern of disrupted maturation during adolescence, with the potential for later changes that may be a result of disease neurotoxicity, abnormal or excessive aging effects, as well as medication, cohort or other effects. Thus, when considering white matter integrity in psychosis, it is critical to consider age in addition to other contributing factors including disease specific effects. Discovery of the factors driving healthy white matter development across the lifespan and deviations from the normal developmental trajectory may provide insights relevant to the discovery of early treatment interventions.

  12. Minimally invasive surgical staging in early stage ovarian carcinoma: a systematic review and meta-analysis.

    PubMed

    Bogani, Giorgio; Borghi, Chiara; Leone Roberti Maggiore, Umberto; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Lopez, Carlos; Sabatucci, Ilaria; Scaffa, Cono; Indini, Alice; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

    2017-02-18

    Few studies investigated the efficacy and safety of minimally invasive surgery (MIS) for the treatment of early stage epithelial ovarian cancer (eEOC). In this context, we aimed to review the current evidence comparing laparoscopy and laparotomic approach for staging procedures in eEOC This systematic review was registered in the International Prospective Register of Systematic Review. Overall, 3,065 patients were included: 1,450 undergoing laparoscopy and 1,615 undergoing laparotomic staging. Patients undergoing laparoscopy experienced a longer (but not statistically significant) operative time (WMD: 28.3 minutes; 95%CI: -2.59, 59.2), lower estimated blood loss (WMD: -156.5 ml; 95%CI: -216.4, -96.5), shorter length of hospital stay (WMD: -3.7 days; 95%CI: -5.2, -2.1) and lower postoperative complication rate (OR: 0.48; 95%CI: 0.29, 0.81) than patients undergoing laparotomy. Upstaging (OR: 0.81; 95%CI: 0.55, 1.20) and cysts' rupture (OR: 1.32; 95%CI: 0.52, 3.38) rates were similar between groups. Laparoscopic staging is associated with a shorter time to chemotherapy than laparotomic procedures (WMD: -5.16 days; 95%CI: -8.68, -1.64). Survival outcomes were not influence by route of surgery. Pooled data suggested that MIS approach is equivalent to laparotomy for the treatment of eEOC and may be superior in terms of perioperative outcomes. However, owing to the low level of evidence of the included studies, further prospective randomized trials are warranted.

  13. Caregiver burden and coping in early-stage Alzheimer disease.

    PubMed

    Zucchella, Chiara; Bartolo, Michelangelo; Pasotti, Chiara; Chiapella, Laura; Sinforiani, Elena

    2012-01-01

    This study was set out to describe caregiver-perceived burden and coping in early-stage Alzheimer disease (AD). A total of 163 consecutive pairs of patients with AD and their principal caregivers were initially recruited. The caregivers completed the Caregiver Burden Inventory (CBI) and the Coping Orientations to Problems Experienced scale, and also provided sociodemographic information; the patients with AD were assessed by means of the Mini Mental State Examination and the Neuropsychiatric Inventory. Data from 126 patient-caregiver pairs were analyzed. The caregivers (mean age 56.11±12.37 y) were mainly women (76%); 64% were the patient's offspring; 39% lived with the patient. From the CBI data, it emerged that caregivers perceived loss of personal time (objective burden, 33%) and the feeling of missing out on opportunities (developmental burden, 25%) as their main stressors. Total CBI score was negatively correlated with Mini Mental State Examination (P=0.005). As regards coping strategies, the caregivers predominantly used problem-oriented strategies associated with a positive attitude. The use of dysfunctional strategies was predictive of caregiver burden. It is important to be aware that avoidance and dysfunctional coping strategies predispose caregivers of patients with AD to higher level of distress, whereas successful caregiving seems to be based on the use of problem-oriented strategies early in the disease when solutions are still available.

  14. Treatment of early-stage Hodgkin lymphoma.

    PubMed

    Engert, Andreas; Raemaekers, John

    2016-07-01

    Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed.

  15. Native language change during early stages of second language learning.

    PubMed

    Bice, Kinsey; Kroll, Judith F

    2015-11-11

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill.

  16. Native language change during early stages of second language learning

    PubMed Central

    Bice, Kinsey; Kroll, Judith F.

    2015-01-01

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The co-activation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as the second language (L2). The present study asked whether L1 change can be detected at early stages of L2 learning and how it is modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials (ERPs) were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared to noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. Additionally, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that the L2 affects the L1 only when L2 speakers are highly proficient, L2 learning begins to impact the L1 early in the development of L2 skill. PMID:26351964

  17. Silicon: The key element in early stages of biocalcification.

    PubMed

    Matsko, Nadejda B; Znidaršič, Nada; Letofsky-Papst, Ilse; Dittrich, Maria; Grogger, Werner; Strus, Jasna; Hofer, Ferdinand

    2011-04-01

    Biocalcification is a widespread process of forming hard tissues like bone and teeth in vertebrates. It is also a topic connecting life sciences and earth sciences: calcified skeletons and shells deposited as sediments represent the earth's fossil record and are of paramount interest for biogeochemists trying to get an insight into the past of our planet. This study reports on the role of silicon in the early biocalcification steps, where silicon and calcium were detected on the surface of cyanobacteria (initial stage of lacustrine calcite precipitation) and in crustacean cuticles. By using innovative methodological approaches of correlative microscopy (AFM in combination with analytical TEM: EFTEM, EELS) the chemical form of silicon in biocalcifying matrices and organic-inorganic particles is determined. Previously, silicon was reported to be localized in active growth areas in the young bone of vertebrates. We have found evidence that biocalcification in evolutionarily distant organisms involves very similar initial phases with silicon as a key element at the organic-inorganic interface.

  18. Cytonuclear incompatibility contributes to the early stages of speciation.

    PubMed

    Barnard-Kubow, Karen B; So, Nina; Galloway, Laura F

    2016-12-01

    Genetic incompatibility is a hallmark of speciation. Cytonuclear incompatibilities are proposed to be among the first genetic barriers to arise during speciation. Accordingly, reproductive isolation (RI) within species should be heavily influenced by interactions between the organelle and nuclear genomes. However, there are few clear examples of cytonuclear incompatibility within a species. Here, we show substantial postzygotic RI in first-generation hybrids between differentiated populations of an herbaceous plant (up to 92% reduction in fitness). RI was primarily due to germination and survival, with moderate RI for pollen viability. RI for survival was asymmetric and caused by cytonuclear incompatibility, with the strength of incompatibility linearly related to chloroplast genetic distance. This cytonuclear incompatibility may be the result of a rapidly evolving plastid genome. Substantial asymmetric RI was also found for germination, but was not associated with cytonuclear incompatibility, indicating endosperm or maternal-zygote incompatibilities. These results demonstrate that cytonuclear incompatibility contributes to RI within species, suggesting that initial rates of speciation could be influenced by rates of organelle evolution. However, other genetic incompatibilities are equally important, indicating that even at early stages, speciation can be a complex process involving multiple genes and incompatibilities.

  19. Life satisfaction of women in early stages of fertility treatment.

    PubMed

    Ben Shlomo, Shirley; Pascal, Mor; Taubman Ben-Ari, Orit; Azuri, Yoseph; Horowtz, Eran

    2016-04-19

    As many women perceive motherhood to be a central component of identity that enhances life satisfaction, difficulties conceiving may lead to stress. This study examined women in the early stages of fertility treatment to ascertain the relations of perceived stress, cognitive appraisal, and self-mastery to the life satisfaction of women embarking on fertility treatment and whether the associations were the same for women who were already mothers versus those who were not. Women were recruited for the study over a period of 18 months, from January 2013 to June 2014. The final sample was composed of 145 women; of these, 67 had 1 or 2 children and 78 had no children. No significant differences were found in perceived stress and life satisfaction between women with and without children. However, in the sample as a whole, higher levels of self-mastery and lower levels of stress were associated with greater life satisfaction. Moreover, the associations between self-mastery and cognitive appraisals of threat and self-efficacy were mediated by perceived stress. The findings highlight the importance of developing interventions at fertility clinics that begin at the very first point of contact to promote the psychological well-being of women being treated for infertility.

  20. Endoscopic mucosal resection of early stage colon neuroendocrine carcinoma

    PubMed Central

    Yamasaki, Yasushi; Uedo, Noriya; Ishihara, Ryu; Tomita, Yasuhiko

    2015-01-01

    Early stage colorectal neuroendocrine carcinoma is rare. A small colon tumour was found in a 56-year-old man during diagnostic colonoscopy performed after a positive faecal occult blood test, and he was referred for treatment. A slightly reddish superficial elevated lesion with a shallow depression 10 mm in size was found in the transverse colon. Magnifying narrow-band imaging revealed disrupted irregular microvessels and the absence of a surface pattern in the depressed area. En bloc endoscopic mucosal resection (EMR) of the tumour was undertaken. The tumour was positive for chromogranin A and synaptophysin, and had a mitotic rate of >20/10 high-power fields and a Ki-67 proliferative index of >50%; it was diagnosed as a neuroendocrine carcinoma. The tumour minimally invaded the submucosa (300 μm) without lymphovascular involvement. The patient was followed up carefully, and at 1 year after EMR, no recurrence was found using colonoscopy and CT scans. PMID:25737221

  1. Toxicity of TFM lampricide to early life stages of walleye

    USGS Publications Warehouse

    Seelye, J.G.; Marking, L.L.; King, E.L.; Hanson, L.H.; Bills, T.D.

    1987-01-01

    The authors studied the effects of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) on gametes, newly fertilized eggs, eyed eggs, larvae, and swim-up fry of the walleye Stizostedion vitreum . When gametes from sexually mature walleyes were stripped into solutions of TFM, no effects were observed during the fertilization process at concentrations up to 3.0 mg/L - three times the concentration lethal to 99.9% of larval sea lampreys Petromyzon marinus held 12 h (LC99.9) under the same test conditions. Newly fertilized eggs likewise were unaffected during water hardening by concentrations of TFM that were lethal to sea lamprey ammocoetes. Eyed eggs, sac fry, and swim-up fry yielded LC25 values that were 2.5 to 5 times greater than the 12-h LC99.9 for sea lamprey ammocoetes. The data thus indicated that all of the early life stages of walleyes tested were considerably more resistant than sea lamprey ammocoetes to TFM, and that it is unlikely they would be adversely affected by standard stream treatments to kill sea lamprey ammocoetes.

  2. Blood biomarkers in the early stage of cerebral ischemia.

    PubMed

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed.

  3. The Early Stages of Groundwater-fed River Bifurcation

    NASA Astrophysics Data System (ADS)

    Yi, R.; Seybold, H. F.; Gibbins, G.; Rothman, D.

    2014-12-01

    Recent work shows, both theoretically and empirically, that river networks fed by subsurface flow bifurcate on average at an angle of 2π/5 [1]. However, the network's existence within a complex natural framework obscures the emergence of this pattern. Fortunately, this ambiguity betrays the presence of processes that have had some effect on the channels during the network's long history. In particular, we concern ourselves with the signature of the third dimension - the topographic relief - on the early stages of channel bifurcation. While, on average, channels grow in a direction dictated by the shape of the groundwater table, we hypothesize that the valley relief plays a crucial role in determining the opening angle and its relaxation to 2π/5 in this regime. A network-wide averaging of several thousand channel bifurcations driven by subsurface flow on the Florida Panhandle reveals that rivers on average branch initially at an angle wider than 2π/5, yet quickly relax to 2π/5 after a few meters. We hypothesize that this initial wide growth direction is governed by the shape of the topography. As these channels form independent valleys, the Laplacian field prevails, yielding an emergent 2π/5 branching angle. Our results therefore suggest that the path-selection of incipient channels fed by subsurface flow is coupled both to the local topography and the surrounding groundwater field. 1. Devauchelle, Olivier, et al. "Ramification of stream networks." Proceedings of the National Academy of Sciences 109.51 (2012): 20832-20836.

  4. Affective Motives for Smoking Among Early Stage Smokers

    PubMed Central

    Wahlquist, Amy E.; Garrett-Mayer, Elizabeth; Gray, Kevin M.; Saladin, Michael E.; Carpenter, Matthew J.

    2014-01-01

    Background: As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Methods: Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16–20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Results: Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR − NR), such that higher dependence was associated with more prominent NR motives for smoking. Conclusions: Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. PMID:24924155

  5. Protein dynamics modulated electron transfer kinetics in early stage photosynthesis

    NASA Astrophysics Data System (ADS)

    Kundu, Prasanta; Dua, Arti

    2013-01-01

    A recent experiment has probed the electron transfer kinetics in the early stage of photosynthesis in Rhodobacter sphaeroides for the reaction center of wild type and different mutants [Science 316, 747 (2007)]. By monitoring the changes in the transient absorption of the donor-acceptor pair at 280 and 930 nm, both of which show non-exponential temporal decay, the experiment has provided a strong evidence that the initial electron transfer kinetics is modulated by the dynamics of protein backbone. In this work, we present a model where the electron transfer kinetics of the donor-acceptor pair is described along the reaction coordinate associated with the distance fluctuations in a protein backbone. The stochastic evolution of the reaction coordinate is described in terms of a non-Markovian generalized Langevin equation with a memory kernel and Gaussian colored noise, both of which are completely described in terms of the microscopics of the protein normal modes. This model provides excellent fits to the transient absorption signals at 280 and 930 nm associated with protein distance fluctuations and protein dynamics modulated electron transfer reaction, respectively. In contrast to previous models, the present work explains the microscopic origins of the non-exponential decay of the transient absorption curve at 280 nm in terms of multiple time scales of relaxation of the protein normal modes. Dynamic disorder in the reaction pathway due to protein conformational fluctuations which occur on time scales slower than or comparable to the electron transfer kinetics explains the microscopic origin of the non-exponential nature of the transient absorption decay at 930 nm. The theoretical estimates for the relative driving force for five different mutants are in close agreement with the experimental estimates obtained using electrochemical measurements.

  6. Dream features in the early stages of Parkinson's disease.

    PubMed

    Bugalho, Paulo; Paiva, Teresa

    2011-11-01

    Few studies have investigated the relation between dream features and cognition in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients' dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient's dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.

  7. [Effects of early growth stage shading on rice flag leaf physiological characters and grain growth at grain-filling stage].

    PubMed

    Liu, Qi-hua; Zhou, Xue-biao; Yang, Lian-qun; Li, Tian; Zhang, Jian-jun

    2009-09-01

    In a pot experiment, rice plants were shaded during the period from transplanting to booting, aimed to study the effects of early growth stage shading on the rice growth at grain-filling stage. Comparing with the control, early growth stage shading decreased the tiller number by 26.72%, but increased the flag leaf area and soluble sugar content by 33.86% and 30.23%, respectively. The filled-grain number per panicle, 1000-grain mass, ultimate brown rice mass, and maximum and average grain-filling rates decreased by 8.65%, 4.81%, 9.74%, 20.22%, and 19.13%, and the effective panicle number and grain yield declined by 25.26% and 39.56%, respectively. The peak time of grain-filling rate (Tm) advanced 1.66 days, while the grain-filling time (T99) prolonged 6.80 days. For shading-tolerance variety, its flag leaf Chl a, Chl b, and Chl (a + b) contents at early and mid grain-filling stages, and the protein N and soluble sugar contents and Chl a/b in its flag leaves at grain-filling stage all increased under early growth stage shading, and the ultimate brown rice mass and 1000-grain mass maintained at the similar levels as the control. Consequently, its grain yield reduction rate was lower than that of shading-sensitive variety.

  8. Susceptibility of early life stages of Xenopus laevis to cadmium

    SciTech Connect

    Herkovits, J.; Perez-Coll, C.S.; Cardellini, P.; Pavanati, C.

    1997-02-01

    The susceptibility of Xenopus laevis to cadmium during different stages of development was evaluated by exposing embryos to cadmium concentrations ranging from 0.1 to 10 mg Cd{sup 2+}/L for 24, 48, and 72 h and assessing lethality and malformations. Susceptibility increased from the two blastomeres stage (stage 2) to stage 40, in which the 24-h LC100 was 1.13 mg Cd{sup 2+}/L, and resistance increased from this stage onward. Malformations occurred at all developmental stages evaluated, the most common being reduced size, incurvated axis, underdeveloped or abnormally developed fin, microcephaly, and microphtalmy. Scanning electron microscopy revealed changes in the ectodermal surface ranging from slightly vaulted cells to a severe reduction in the number of ciliated cells as the concentration of cadmium increased. The intraspecific variation evaluated in embryos (from four sets of parents) at seven developmental stages, expressed as the coefficient of variation of the LC100, ranged from 10 to 112% and reflects the capacity of Xenopus laevis to adapt to changing environmental conditions at different embryonic stages.

  9. To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

    ERIC Educational Resources Information Center

    Wöhrer, Veronika

    2014-01-01

    Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

  10. Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

    PubMed Central

    2014-01-01

    Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

  11. Using Motivational Interviewing within the Early Stages of Group Development

    ERIC Educational Resources Information Center

    Young, Tabitha L.

    2013-01-01

    This article presents developmentally appropriate applications of Motivational Interviewing (MI; Miller & Rollnick, 2002) for use in preparing group members for the working stages of group. Practical strategies are offered for using MI to facilitate an atmosphere of trust, recognize member readiness for change, identify and resolve members'…

  12. POLLUTION PREVENTION IN THE EARLY STAGES OF HIERARCHICAL PROCESS DESIGN

    EPA Science Inventory

    Hierarchical methods are often used in the conceptual stages of process design to synthesize and evaluate process alternatives. In this work, the methods of hierarchical process design will be focused on environmental aspects. In particular, the design methods will be coupled to ...

  13. Efficient embryonic culture method for the Japanese striped snake, Elaphe quadrivirgata, and its early developmental stages.

    PubMed

    Matsubara, Yoshiyuki; Sakai, Atsushi; Kuroiwa, Atsushi; Suzuki, Takayuki

    2014-10-01

    The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo.

  14. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    PubMed

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations.

  15. ERP Evidence of Visualization at Early Stages of Visual Processing

    ERIC Educational Resources Information Center

    Page, Jonathan W.; Duhamel, Paul; Crognale, Michael A.

    2011-01-01

    Recent neuroimaging research suggests that early visual processing circuits are activated similarly during visualization and perception but have not demonstrated that the cortical activity is similar in character. We found functional equivalency in cortical activity by recording evoked potentials while color and luminance patterns were viewed and…

  16. Early Years Foundation Stage: How Much Does It Count?

    ERIC Educational Resources Information Center

    Thompson, Ian

    2008-01-01

    The final report of the Williams committee (DCSF, 2008: 68) argues that the revised mathematics Framework (DfES, 2006) "should be reconsidered to achieve a more suitable, user-friendly form." It might also have added that there is not much help and support in it for early years teachers. A much more useful document is the "Practice guidance for…

  17. CMB quadrupole suppression. II. The early fast roll stage

    NASA Astrophysics Data System (ADS)

    Boyanovsky, D.; de Vega, H. J.; Sanchez, N. G.

    2006-12-01

    Within the effective field theory of inflation, an initialization of the classical dynamics of the inflaton with approximate equipartition between the kinetic and potential energy of the inflaton leads to a brief fast roll stage that precedes the slow roll regime. The fast roll stage leads to an attractive potential in the wave equations for the mode functions of curvature and tensor perturbations. The evolution of the inflationary perturbations is equivalent to the scattering by this potential and a useful dictionary between the scattering data and observables is established. Implementing methods from scattering theory we prove that this attractive potential leads to a suppression of the quadrupole moment for CMB and B-mode angular power spectra. The scale of the potential is determined by the Hubble parameter during slow roll. Within the effective field theory of inflation at the grand unification (GUT) energy scale we find that if inflation lasts a total number of e-folds Ntot˜59, there is a 10% 20% suppression of the CMB quadrupole and about 2% 4% suppression of the tensor quadrupole. The suppression of higher multipoles is smaller, falling off as 1/l2. The suppression is much smaller for Ntot>59, therefore if the observable suppression originates in the fast roll stage, there is the upper bound Ntot˜59.

  18. Radiotherapy Alone for Early-Stage Squamous Cell Carcinoma of the Larynx and Hypopharynx

    SciTech Connect

    Foote, Robert L.

    2007-10-01

    Purpose: To describe and illustrate examples of early-stage larynx and hypopharynx cancer that can be successfully treated with radiotherapy alone. Methods and Materials: Review of the NCCN and ASCO practice guidelines. Representative examples are included. Results: Early-stage larynx and hypopharynx cancer is defined by tumor extent based on physical and imaging examination. Conclusions: Radiotherapy alone is appropriate treatment for properly selected early-stage squamous cell carcinoma of the larynx and hypopharynx. The NCCN and ASCO practice guidelines can be an aid to the clinician in identifying favorable cancers that can be successfully treated with radiotherapy alone with preservation of organ function.

  19. [Anxiety-phobic disorders in the early childhood stage].

    PubMed

    Volkova, O M; Kozlovskaia, G V; Proselkova, M O

    2012-01-01

    The complex of such phenomena as anxiety and fear in children of the early age and their relationship with risk factors for psychic pathology were investigated. Eighty cases of anxiety-phobic disorders in children of the first five years of life were studied. The types of behavioral and somatic reactions that allowed to reveal not only the clinically expressed phenomena of anxiety and fear but the higher readiness to them were described. The first anxiety-phobic reactions appeared at the age when emotional functions were not completely formed and might be considered as the presentations of emotional dysontogenesis. The authors assume that characteristics of fear expression in the early age allow to suspect a mental disease which might be timely diagnosed in case of its manifestation. The conclusions made in the paper may be useful for clinical practice of pediatricians, children neurologists, psychologists and psychiatrists.

  20. Signs of Early-stage Disk Growth Revealed with ALMA

    NASA Astrophysics Data System (ADS)

    Yen, Hsi-Wei; Koch, Patrick M.; Takakuwa, Shigehisa; Krasnopolsky, Ruben; Ohashi, Nagayoshi; Aso, Yusuke

    2017-01-01

    We present ALMA 1.3 mm continuum, 12CO, C18O, and SO data for the Class 0 protostars Lupus 3 MMS, IRAS 15398‑3559, and IRAS 16253‑2429 at resolutions of ∼100 au. By measuring a rotational profile in C18O, a 100 au Keplerian disk around a 0.3 M⊙ protostar is observed in Lupus 3 MMS. No 100 au Keplerian disks are observed in IRAS 15398‑3559 and IRAS 16253‑2429. Nevertheless, embedded compact (<30 au) continuum components are detected. The C18O emission in IRAS 15398‑3559 shows signatures of infall with a constant angular momentum. IRAS 16253‑2429 exhibits signatures of infall and rotation, but its rotational profile is unresolved. By fitting the C18O data with our kinematic models, the protostellar masses and the disk radii are inferred to be 0.01 M⊙ and 20 au in IRAS 15398‑3559, and 0.03 M⊙ and 6 au in IRAS 16253‑2429. By comparing the specific angular momentum profiles from 10,000 au to 100 au in eight Class 0 and I protostars, we find that the evolution of envelope rotation can be described with conventional inside-out collapse models. In comparison with a sample of 18 protostars with known disk radii, our results reveal signs of disk growth, with the disk radius increasing as {{M}* }0.8+/- 0.14 or {t}1.09+/- 0.37 in the Class 0 stage, where M* is the protostellar mass and t is the age. The disk growth rate slows down in the Class I stage. In addition, we find a hint that the mass accretion rate declines as {t}-0.26+/- 0.04 from the Class 0 to the Class I stages.

  1. Estramustine phosphate reversibly inhibits an early stage during adenovirus replication.

    PubMed

    Everitt, E; Ekstrand, H; Boberg, B; Hartley-Asp, B

    1990-01-01

    Estramustine phosphate, an estradiol-mustard conjugate, was shown to reversibly inhibit a stage during the first hour of productive adenovirus 2 infection of HeLa cells. This drug, employed in the therapy of advanced prostatic cancer, specifically interacts with microtubule-associated proteins (MAPs) of the cytoskeleton. The results obtained under physiological conditions in vivo suggest a MAPs-interference with the microtubule-mediated vectorial migration of the virus inoculum to the nucleus. Virus attachment, uncoating kinetics and the appearance of established uncoating intermediates were not affected.

  2. Features controlling the early stages of creep deformation of Waspaloy

    NASA Technical Reports Server (NTRS)

    Ferrari, A.; Wilson, D. J.

    1974-01-01

    A model has been presented for describing primary and second stage creep. General equations were derived for the amount and time of primary creep. It was shown how the model can be used to extrapolate creep data. Applicability of the model was demonstrated for Waspaloy with gamma prime particle sizes from 75 - 1000 A creep tested in the temperature range 1000 - 1400 F (538 - 760 C). Equations were developed showing the dependence of creep parameters on dislocation mechanism, gamma prime volume fraction and size.

  3. Screening of early antigen genes of adult-stage Trichinella spiralis using pig serum from different stages of early infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this work was to identify novel, early antigens present in Trichinella spiralis. To this end, a cDNA library generated from 3-day old adult worms (Ad3) was immunologically screened using serum from a pig infected with 20,000 muscle larvae. The serum was obtained from multiple, time cours...

  4. Formal Verification Toolkit for Requirements and Early Design Stages

    NASA Technical Reports Server (NTRS)

    Badger, Julia M.; Miller, Sheena Judson

    2011-01-01

    Efficient flight software development from natural language requirements needs an effective way to test designs earlier in the software design cycle. A method to automatically derive logical safety constraints and the design state space from natural language requirements is described. The constraints can then be checked using a logical consistency checker and also be used in a symbolic model checker to verify the early design of the system. This method was used to verify a hybrid control design for the suit ports on NASA Johnson Space Center's Space Exploration Vehicle against safety requirements.

  5. Fully compressible solutions for early stage Richtmyer–Meshkov instability

    SciTech Connect

    Margolin, Len G.; Reisner, Jon Michael

    2016-10-27

    Here, we will consider the effects of compressibility and viscosity on the early dynamics of the Richtmyer–Meshkov instability (RMI). In particular, we will combine theory, scaling, and high resolution simulation of RMI to probe the details of the initial compression and the subsequent viscous damping as a shock interacts with a density discontinuity. We will propose a refinement of the classic 1D model for the linear regime of RMI that, for small initial perturbation wavelengths, more accurately reproduces the 2D dynamics of a fully resolved numerical simulation.

  6. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

    Cancer.gov

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

  7. [Predictive value of Ages & Stages Questionnaires for cognitive performance at early years of schooling].

    PubMed

    Schonhaut B, Luisa; Pérez R, Marcela; Castilla F, Ana María; Castro M, Sonia; Salinas A, Patricia; Armijo R, Iván

    2017-02-01

    The Ages and Stages questionnaires (ASQ) has been recently validated in our country for developmental screening. The objective of this study is evaluate the validity of ASQ to predict low cognitive performance in the early years of schooling.

  8. New NIA Booklet By and For People With Early-Stage Alzheimer's Disease

    MedlinePlus

    ... Booklet By and For People With Early-Stage Alzheimer's Disease Past Issues / Fall 2007 Table of Contents For ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going through ...

  9. Dutasteride May Slow the Growth of Early-Stage Prostate Cancer | Division of Cancer Prevention

    Cancer.gov

    For men who are undergoing active surveillance for early-stage prostate cancer, the drug dutasteride (Avodart) could help control the disease and prevent the need for more aggressive treatments. |

  10. Late Effects May Not Warrant Using Radiation to Treat Early-Stage Hodgkin Lymphoma

    Cancer.gov

    Patients with early-stage Hodgkin lymphoma who were treated with multidrug chemotherapy alone were more likely to be alive 12 years later than patients who received treatment that included radiation therapy, according to findings from a clinical trial.

  11. Analysis on Gene Expression Profile in Oncospheres and Early Stage Metacestodes from Echinococcus multilocularis

    PubMed Central

    Dang, Zhisheng; Suzuki, Yutaka; Horiuchi, Terumi; Yagi, Kinpei; Kouguchi, Hirokazu; Irie, Takao; Kim, Kyeongsoon; Oku, Yuzaburo

    2016-01-01

    Alveolar echinococcosis is a worldwide zoonosis of great public health concern. Analysis of genome data for Echinococcus multilocularis has identified antigen families that can be used in diagnostic assays and vaccine development. However, little gene expression data is available for antigens of the egg and early larval stages. To address this information gap, we used a Next-Generation Sequencing approach to investigate three different stages (non-activated and activated oncospheres, and early stage metacestodes) of E. multilocularis (Nemuro strain). Transcriptome data analysis revealed that some diagnostic antigen gp50 isoforms and the antigen Eg95 family dominated in activated oncospheres, and the antigen B family dominated in early stage metacestodes. Furthermore, heat shock proteins and antigen II/3 are constantly expressed in the three stages. The expression pattern of various known antigens in E. multilocularis may give fundamental information for choosing candidate genes used in diagnosis and vaccine development. PMID:27092774

  12. Staging Life in an Early Warm ‘Seltzer’ Ocean

    SciTech Connect

    Schoonen, Martin; Smirnov, Alexander

    2016-12-01

    A period as short as 20 million years within the first 100 million years after the formation of the Moon may have set the stage for the origin of life. This atmosphere contained more carbon dioxide than any other period afterwards. The carbon dioxide sustained greenhouse conditions, accelerated the weathering of a primitive crust and may have led to conditions conducive to the formation of the building blocks of life. The conversion of CO2 as well as N2 may have been facilitated by clays, zeolites, sulfides and metal alloys formed as the crust reacted with a warm ‘seltzer’ ocean. We used geochemical modeling to constrain the conditions favorable for the formation of these potential mineral catalysts.

  13. Staging Life in an Early Warm ‘Seltzer’ Ocean

    DOE PAGES

    Schoonen, Martin; Smirnov, Alexander

    2016-12-01

    A period as short as 20 million years within the first 100 million years after the formation of the Moon may have set the stage for the origin of life. This atmosphere contained more carbon dioxide than any other period afterwards. The carbon dioxide sustained greenhouse conditions, accelerated the weathering of a primitive crust and may have led to conditions conducive to the formation of the building blocks of life. The conversion of CO2 as well as N2 may have been facilitated by clays, zeolites, sulfides and metal alloys formed as the crust reacted with a warm ‘seltzer’ ocean. Wemore » used geochemical modeling to constrain the conditions favorable for the formation of these potential mineral catalysts.« less

  14. Problem solving, impulse control and planning in patients with early- and late-stage Huntington's disease.

    PubMed

    Mörkl, Sabrina; Müller, Nicole J; Blesl, Claudia; Wilkinson, Leonora; Tmava, Adelina; Wurm, Walter; Holl, Anna K; Painold, Annamaria

    2016-10-01

    Sub-domains of executive functions, including problems with planning, accuracy, impulsivity, and inhibition, are core features of Huntington's disease. It is known that the decline of cognitive function in Huntington's disease is related to the anatomical progression of pathology in the basal ganglia. However, it remains to be determined whether the severity of executive dysfunction depends on the stage of the disease. To examine the severity of sub-domains of executive dysfunction in early- and late-stage Huntington's disease, we studied performance in the Tower of London task of two groups of Huntington's disease patients (Group 1: early, n = 23, and Group 2: late stage, n = 29), as well as a third group of age, education, and IQ matched healthy controls (n = 34). During the task, we measured the total number of problems solved, total planning time, and total number of breaks taken. One aspect of executive function indexed by the number of solved problems seems to progress in the course of the disease. Late-stage Huntington's disease patients scored significantly worse than early-stage patients and controls, and early-stage patients scored significantly worse than controls on this measure of accuracy. In contrast, late- and early-stage HD patients did not differ in terms of planning time and number of breaks. Early- and late-stage HD pathology has a different impact on executive sub-domains. While accuracy differs between early- and late-stage HD patients, other domains like planning time and number of breaks do not. Striatal degeneration, which is a characteristic feature of the disease, might not affect all aspects of executive function in HD.

  15. Serum markers in early-stage and locally advanced melanoma.

    PubMed

    Lugowska, Iwona; Kowalska, Maria; Fuksiewicz, Małgorzata; Kotowicz, Beata; Mierzejewska, Ewa; Koseła-Paterczyk, Hanna; Szamotulska, Katarzyna; Rutkowski, Piotr

    2015-11-01

    The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I-III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7%; 35 patients died; and the 3-year overall survival (OS) rate was 85%. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61% (p = 0.014) and overall survival -88 vs. 82% (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59% of patients with ulceration and in 26% of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I-III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.

  16. Upper thermal tolerances of early life stages of freshwater mussels

    USGS Publications Warehouse

    Pandolfo, Tamara J.; Cope, W. Gregory; Arellano, Consuelo; Bringolf, Robert B.; Barnhart, M. Christopher; Hammer, E

    2010-01-01

    Freshwater mussels (order Unioniformes) fulfill an essential role in benthic aquatic communities, but also are among the most sensitive and rapidly declining faunal groups in North America. Rising water temperatures, caused by global climate change, industrial discharges, drought, or land development, could further challenge imperiled unionid communities. The aim of our study was to determine the upper thermal tolerances of the larval (glochidia) and juvenile life stages of freshwater mussels. Glochidia of 8 species of mussels were tested: Lampsilis siliquoidea, Potamilus alatus, Ligumia recta, Ellipsaria lineolata,Lasmigona complanata, Megalonaias nervosa, Alasmidonta varicosa, and Villosa delumbis. Seven of these species also were tested as juveniles. Survival trends were monitored while mussels held at 3 acclimation temperatures (17, 22, and 27°C) were exposed to a range of common and extreme water temperatures (20–42°C) in standard acute laboratory tests. The average median lethal temperature (LT50) among species in 24-h tests with glochidia was 31.6°C and ranged from 21.4 to 42.7°C. The mean LT50 in 96-h juvenile tests was 34.7°C and ranged from 32.5 to 38.8°C. Based on comparisons of LT50s, thermal tolerances differed among species for glochidia, but not for juveniles. Acclimation temperature did not affect thermal tolerance for either life stage. Our results indicate that freshwater mussels already might be living close to their upper thermal tolerances in some systems and, thus, might be at risk from rising environmental temperatures.

  17. Microbial Diversity within Early-Stage Cultured Panulirus ornatus Phyllosomas▿

    PubMed Central

    Payne, Matthew S.; Hall, Mike R.; Sly, Lindsay; Bourne, David G.

    2007-01-01

    A thorough understanding of the microorganisms and pathogens associated with the larval stage of the tropical ornate rock lobster, Panulirus ornatus, is required to overcome disease outbreaks that currently block aquaculture attempts. This study used microscopy in addition to culture and molecularly based microbiological techniques to characterize the bacterial community associated with cultured, developmental stage PI to PII P. ornatus phyllosomas. Scanning electron microscopy demonstrated colonization of phyllosomas by filamentous, rod-shaped, and coccus-shaped bacteria. A clone library constructed from dead phyllosomas sampled from the larval rearing tank on day 10 was dominated by Thiothrix-affiliated sequences (56% of clones). A comparable library from live phyllosomas also contained Thiothrix-affiliated sequences, though these only represented 19% of clones within the library. Fluorescent in situ hybridization (FISH) confirmed identification of the filamentous bacteria as Thiothrix sp., being present on dead phyllosomas. FISH also identified Leucothrix sp. and Vibrio sp., as well as a range of other rod- and coccus-shaped bacteria, colonizing both live and dead phyllosomas. The development of the microbial community associated with phyllosomas was monitored through a standard larval rearing run using denaturing gradient gel electrophoresis (DGGE). Vibrio sp.-affiliated bands dominated the profiles of live animals through the rearing period and dead phyllosomas sampled on selected days. The population of Vibrio sp. associated with phyllosomas was monitored with culture-based analysis on selective media and demonstrated to increase significantly on day 7, coinciding with the beginning of the larval molt. An isolated Vibrio harveyi strain demonstrated an identical 16S rRNA sequence with retrieved DGGE and clone library sequences. Colonization of phyllosomas with filamentous bacterial species potentially hinders the ability of the animals to molt and, combined

  18. Shipboard Electrical System Modeling for Early-Stage Design Space Exploration

    DTIC Science & Technology

    2013-04-01

    Shipboard Electrical System Modeling for Early -Stage Design Space Exploration Aaron M. Cramer, Hanling Chen Department of Electrical and Computer...Department United States Naval Academy Annapolis, MD, USA Email: zivi@usna.edu Abstract—In early -stage design exploration, it has been found that...involved the use of linear programming to model the action of the power system [6]. In this approach, the mechanical dynamics associated with prime movers

  19. Alternatives to surgery in early stage disease—stereotactic body radiotherapy

    PubMed Central

    Giuliani, Meredith Elana

    2013-01-01

    The management of early stage non-small cell lung carcinoma (NSCLC) has been revolutionized by the introduction of stereotactic body radiotherapy (SBRT). SBRT is now the standard of care for medically inoperable patients with early stage NSCLC. However, the role of SBRT in medically operable patients remains controversial. This article will review the indications, the technical considerations, image guidance principles, potential toxicities and special circumstances in lung SBRT. PMID:25806252

  20. Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2014-10-01

    Award Number: W81XWH-12-1-0521 TITLE: Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0521 Identification of a Genomic Signature Predicting for Recurrence in Early-Stage...clinical annotation and accurate pathological review (228 recurrent and 364 non-recurrent), 2) established a specimen repository and clinical data

  1. Confidence Interval Estimation for Sensitivity to the Early Diseased Stage Based on Empirical Likelihood.

    PubMed

    Dong, Tuochuan; Tian, Lili

    2015-01-01

    Many disease processes can be divided into three stages: the non-diseased stage: the early diseased stage, and the fully diseased stage. To assess the accuracy of diagnostic tests for such diseases, various summary indexes have been proposed, such as volume under the surface (VUS), partial volume under the surface (PVUS), and the sensitivity to the early diseased stage given specificity and the sensitivity to the fully diseased stage (P2). This paper focuses on confidence interval estimation for P2 based on empirical likelihood. Simulation studies are carried out to assess the performance of the new methods compared to the existing parametric and nonparametric ones. A real dataset from Alzheimer's Disease Neuroimaging Initiative (ADNI) is analyzed.

  2. Developmental rate and behavior of early life stages of bighead carp and silver carp

    USGS Publications Warehouse

    Chapman, Duane C.; George, Amy E.

    2011-01-01

    The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

  3. Hydrogenation of iron in the early stage of Earth's evolution

    PubMed Central

    Iizuka-Oku, Riko; Yagi, Takehiko; Gotou, Hirotada; Okuchi, Takuo; Hattori, Takanori; Sano-Furukawa, Asami

    2017-01-01

    Density of the Earth's core is lower than that of pure iron and the light element(s) in the core is a long-standing problem. Hydrogen is the most abundant element in the solar system and thus one of the important candidates. However, the dissolution process of hydrogen into iron remained unclear. Here we carry out high-pressure and high-temperature in situ neutron diffraction experiments and clarify that when the mixture of iron and hydrous minerals are heated, iron is hydrogenized soon after the hydrous mineral is dehydrated. This implies that early in the Earth's evolution, as the accumulated primordial material became hotter, the dissolution of hydrogen into iron occurred before any other materials melted. This suggests that hydrogen is likely the first light element dissolved into iron during the Earth's evolution and it may affect the behaviour of the other light elements in the later processes. PMID:28082735

  4. Detecting early stage osteoarthritis by optical coherence tomography?

    PubMed Central

    Jahr, Holger; Brill, Nicolai; Nebelung, Sven

    2015-01-01

    Abstract Osteoarthritis (OA) is the most common chronic disease of our joints, manifested by a dynamically increasing degeneration of hyaline articular cartilage (AC). While currently no therapy can reverse this process, the few available treatment options are hampered by the inability of early diagnosis. Loss of cartilage surface, or extracellular matrix (ECM), integrity is considered the earliest sign of OA. Despite the increasing number of imaging modalities surprisingly few imaging biomarkers exist. In this narrative review, recent developments in optical coherence tomography are critically evaluated for their potential to assess different aspects of AC quality as biomarkers of OA. Special attention is paid to imaging surface irregularities, ECM organization and the evaluation of posttraumatic injuries by light-based modalities. PMID:26862954

  5. Hydrogenation of iron in the early stage of Earth's evolution

    NASA Astrophysics Data System (ADS)

    Iizuka-Oku, Riko; Yagi, Takehiko; Gotou, Hirotada; Okuchi, Takuo; Hattori, Takanori; Sano-Furukawa, Asami

    2017-01-01

    Density of the Earth's core is lower than that of pure iron and the light element(s) in the core is a long-standing problem. Hydrogen is the most abundant element in the solar system and thus one of the important candidates. However, the dissolution process of hydrogen into iron remained unclear. Here we carry out high-pressure and high-temperature in situ neutron diffraction experiments and clarify that when the mixture of iron and hydrous minerals are heated, iron is hydrogenized soon after the hydrous mineral is dehydrated. This implies that early in the Earth's evolution, as the accumulated primordial material became hotter, the dissolution of hydrogen into iron occurred before any other materials melted. This suggests that hydrogen is likely the first light element dissolved into iron during the Earth's evolution and it may affect the behaviour of the other light elements in the later processes.

  6. Familiarity and Emotional Expression Influence an Early Stage of Face Processing: An Electrophysiological Study

    ERIC Educational Resources Information Center

    Caharel, Stephanie; Courtay, Nolwenn; Bernard, Christian; Lalonde, Robert; Rebai, Mohamed

    2005-01-01

    Recent data indicate that the familiarity and the emotional expression of faces occur at an early stage of information processing. The goal of the present study was to determine whether these two aspects interact at the structural encoding stage as reflected by the N170 component of event-related potentials in tasks requiring the subjects either…

  7. The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases

    PubMed Central

    Braicu, Elena Iona; Sehouli, Jalid; Tauber, Rudolf; Blanchard, Véronique

    2014-01-01

    Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation. PMID:25183900

  8. Advancing Early Detection of Autism Spectrum Disorder by Applying an Integrated Two-Stage Screening Approach

    ERIC Educational Resources Information Center

    Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

    2010-01-01

    Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence…

  9. Dyadic Intervention for Family Caregivers and Care Receivers in Early-Stage Dementia

    ERIC Educational Resources Information Center

    Whitlatch, Carol J.; Judge, Katherine; Zarit, Steven H.; Femia, Elia

    2006-01-01

    Purpose: The Early Diagnosis Dyadic Intervention (EDDI) program provides a structured, time-limited protocol of one-on-one and dyadic counseling for family caregivers and care receivers who are in the early stages of dementia. The goals and procedures of EDDI are based on previous research suggesting that dyads would benefit from an intervention…

  10. Involvement of lysosomes in the early stages of axon degeneration.

    PubMed

    Zheng, Jin; Yan, Tingting; Feng, Yan; Zhai, Qiwei

    2010-02-01

    Axon degeneration is a common hallmark of many neurodegenerative diseases, and the underlying mechanism remains largely unknown. Lysosomes are involved in some neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Whether lysosomes are involved in axon degeneration is yet to be elucidated. In this study, we found only about 10% lysosomes remained in axons of cultured superior cervical ganglia (SCGs) after transection for 4h when stained with LysoTracker. Furthermore, we found that lysosomal disruption occurred earlier than morphological changes and loss of mitochondrial membrane potential. In addition, the well-known axon-protective protein Wld(S) delayed injury-induced axon degeneration from both morphological changes and lysosomal disruption. Lysosomal inhibitors including chloroquine and ammonium chloride induced axon degeneration in cultured SCGs, and Wld(S) also slowed down the axon degeneration induced by lysosomal inhibitors. All these data suggest that lysosomal disruption is an early marker of axon degeneration, and inhibition of lysosome induces axon degeneration in a Wld(S)-protectable way. Thus, maintenance of normal lysosomal function might be an important approach to delay axon degeneration in neurodegenerative diseases.

  11. Prospective Double-Blind Study of Zidovudine (AZT) in Early Stage HIV infection

    DTIC Science & Technology

    1988-05-01

    FRONT COVER FUNDING NO. 87PP7875 S L. TITLE: Prospective Double-Blind Study of Zidovudine (AZT) in Early Stage HIV Infection PRINCIPAL INVESTIGATOR...Prospective Double-Blind Study of Zidovudine (AZT) in Early State HIV Infection 12. PERSONAL AUTHOR(S) Shannon M. Harrison 13a. TYPE OF REPORT 113b...COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUBGROUP HIV , Zidovudine, Early, Infection 06

  12. Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

    PubMed

    Ingley, Spencer J; Johnson, Jerald B

    2016-03-01

    How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time.

  13. Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish

    PubMed Central

    Johnson, Jerald B.

    2016-01-01

    How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. PMID:26979559

  14. Formation of Jupiter's Core and Early Stages of Envelope Accretion

    NASA Astrophysics Data System (ADS)

    D'Angelo, G.; Weidenschilling, S.; Lissauer, J. J.; Bodenheimer, P.; Hubickyj, O.

    2012-12-01

    We are performing calculations of the formation of Jupiter via core nucleated accretion and gas capture. The core starts as a seed body of a few hundred kilometers in radius and orbits within a swarm of planetesimals whose initial size distribution ranges from ~10 m to ~100 km. The planetesimals are immersed in a gaseous disk, representative of an early solar nebula. The evolution of the swarm of planetesimals accounts for collisions and gravitational stirring due to mutual interactions among bodies, and for migration and velocity damping due to interactions with the nebula gas. Collisions among planetesimals lead to growth and/or fragmentation, altering the size distribution of the swarm over time. Collisions of planetesimals with the seed body lead to its growth, resulting in the formation of a planetary core. Gas capture by the core leads to the accumulation of a tenuous atmosphere, which later becomes a massive envelope, increasing the size-dependent effective cross-section of the planet for planetesimals' accretion. Planetesimals that travel through the core's envelope release energy, affecting the thermal budget of the envelope, and deliver mass, affecting the opacity of the envelope. The calculation of dust opacity, which is especially important for envelope contraction, is performed self-consistently, accounting for coagulation and sedimentation of dust and small particles that are released in the envelope as passing planetesimals are ablated. We find that, in a disk of planetesimals with a surface density of about 10 g/cm2 at 5.2 AU, a one Earth mass core accumulates in less than 1e5 years, and that it takes over 1.5e6 years to accumulate a core of 3 Earth masses, when the core's geometrical cross-section is used for the accretion of planetesimals. Gas drag in the core's envelope increases the ability of the planet to accrete planetesimals. Smaller planetesimals are affected to a greater extent than are larger planetesimals. We find that the effective

  15. The Memory Club: Providing support to persons with early-stage dementia and their care partners.

    PubMed

    Gaugler, Joseph E; Gallagher-Winker, Karen; Kehrberg, Kathy; Lunde, Angela M; Marsolek, Connie M; Ringham, Kathryn; Thompson, Gerise; Barclay, Michelle

    2011-05-01

    There is a growing emphasis on delivering services for persons with early-stage dementia (ie, ''persons with memory loss,'' or PWMLs) and their family members (care partners). The goal of this evaluation was to determine whether participation in the Memory Club, a 10- to 13-session joint support group, would result in decreased distress, enhanced preparation for care, and improved feelings of confidence managing the challenges of early-stage dementia. The single group, pre-/post-test evaluation included 63 PWMLs and 61 care partners who participated in three Memory Club sites in Minnesota. Paired T-test results found that care partners reported significant (P < .05) increases in preparation activities, feelings of preparation, and confidence in managing memory loss. The results suggest that the Memory Club can fill an important gap in early-stage dementia care by offering care partners the opportunity to plan, prepare, and increase coping skills in the face of early dementia progression.

  16. Integrative Protein-Based Prognostic Model for Early Stage Endometrioid Endometrial Cancer

    PubMed Central

    Yang, Ji-Yeon; Werner, Henrica M.J.; Li, Jie; Westin, Shannon N.; Lu, Yiling; Halle, Mari K.; Trovik, Jone; Salvesen, Helga B.; Mills, Gordon B.; Liang, Han

    2015-01-01

    Purpose Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. Experimental Design We employed two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. Results Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test p-value = 0.565 for disease stage, 0.567 for tumor grade, 1.3×10−4 for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Conclusions Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies. PMID:26224872

  17. Driving behaviors in early stage dementia: a study using in-vehicle technology.

    PubMed

    Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

    2012-11-01

    According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost.

  18. Comparison of Laparoscopy and Laparotomy in Surgical Staging of Apparent Early Ovarian Cancer

    PubMed Central

    Lu, Qi; Qu, Hong; Liu, Chongdong; Wang, Shuzhen; Zhang, Zhiqiang; Zhang, Zhenyu

    2016-01-01

    Abstract The aim of this study was to compare the safety and morbidity of laparoscopic versus laparotomic comprehensive staging of apparent early stage ovarian cancer. In this retrospective study, the outcomes of patients with apparent stage I ovarian cancer who underwent laparoscopic or laparotomic comprehensive surgical staging from January 2002 to January 2014 were evaluated. The long-term survival of patients with early ovarian cancer was compared. Forty-two patients were treated by laparoscopy, and 50 were treated by laparotomy. The median operative time was 200 minutes in the laparoscopy group and 240 minutes in the laparotomy group (P >0.05). The median length of hospital stay was 3 days in the laparoscopy group and 7 days in the laparotomy group (P <0.05). Following laparoscopic and laparotomic staging, the cancer was upstaged for 9 (21.4%) and 10 (20.0%) women, respectively. The median follow-up time was 82 months in the laparoscopic and laparotomic groups, respectively. Excluding the upstaged patients, no recurrence was observed in the present study, and the overall survival and 5-year survival rates were 100% in both the laparoscopy and laparotomy groups. Laparoscopic and laparotomic comprehensive staging of early ovarian cancer were similar in terms of staging adequacy, accuracy and survival rate. Laparoscopic staging was associated with a significantly reduced hospital stay. Prospective randomized trials are required to evaluate the overall oncologic outcomes. PMID:27196468

  19. Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

    EPA Science Inventory

    Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

  20. Transvaginal Sonography Versus Cystoscopy for Detecting Urinary Bladder Invasion in Early Stage Cervical Cancer

    PubMed Central

    Zutshi, Vijay; Garg, Anju; Batra, Swaraj

    2017-01-01

    Introduction Cervical cancer is a major cause of mortality from cancer among women. In it’s early stage pre operative staging with cystoscopy is a standard procedure for the detection of urinary bladder involvement. Aim The present study was conducted with the aim to compare the efficacy of Transvaginal Sonography (TVS) and cystoscopy in diagnosing bladder involvement in early stage cervical cancer patients by confirming it intraoperatively and further by histopathologic examination. Materials and Methods A prospective partially blinded study was conducted between March 2006 and September 2008 on 30 patients with early stage cervical cancer (Stage I and IIa) who were planned to undergo radical hysterectomy. Pre operatively, these patients underwent both TVS and cystoscopy to diagnose bladder involvement. Presence or absence of bladder involvement was then confirmed intra operatively and by histopathologic examination. Results In all the 30 patients studied, no bladder involvement was seen on cystoscopy where as TVS showed bladder involvement in three patients. Involvement of the bladder in these three patients was confirmed intra operatively and by histopathologic examination. Thus, in our study, TVS was 100% sensitive in detecting bladder involvement. Conclusion TVS is highly sensitive in diagnosing bladder involvement in early stage cervical cancer and could potentially detect cases missed with a cystoscopy.

  1. All-optical photoacoustic imaging and detection of early-stage dental caries

    NASA Astrophysics Data System (ADS)

    Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

    2015-02-01

    Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

  2. Using Spirituality to Cope with Early Stage Alzheimer’s disease

    PubMed Central

    Grando, Victoria T.

    2010-01-01

    Alzheimer’s disease (AD) robs persons living with this disease of their independence and self-esteem, which can lead to depression, anxiety, and loneliness. Understanding how people with early stage AD cope is a critical step to enhance their adaptive abilities and ultimately improve their quality of life. This qualitative study describes how individuals with early stage AD use spirituality to cope with the losses of self-esteem, independence, and social interaction that they face. The purposive sample for this focused ethnography study consisted of 15 participants living at home in central Arkansas. Holding onto faith, seeking reassurance and hope, and staying connected were the global themes. Personal faith, prayer, connection to church, and family support enhanced the ability for people with early stage AD to keep a positive attitude as they face living with Alzheimer’s. PMID:19282270

  3. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development.

  4. Identification of Early-Stage Alzheimer's Disease Using Sulcal Morphology and Other Common Neuroimaging Indices

    PubMed Central

    Cai, Kunpeng; Xu, Hong; Guan, Hao; Zhu, Wanlin; Jiang, Jiyang; Cui, Yue; Zhang, Jicong; Liu, Tao; Wen, Wei

    2017-01-01

    Identifying Alzheimer’s disease (AD) at its early stage is of major interest in AD research. Previous studies have suggested that abnormalities in regional sulcal width and global sulcal index (g-SI) are characteristics of patients with early-stage AD. In this study, we investigated sulcal width and three other common neuroimaging morphological measures (cortical thickness, cortical volume, and subcortical volume) to identify early-stage AD. These measures were evaluated in 150 participants, including 75 normal controls (NC) and 75 patients with early-stage AD. The global sulcal index (g-SI) and the width of five individual sulci (the superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure) were extracted from 3D T1-weighted images. The discriminative performances of the other three traditional neuroimaging morphological measures were also examined. Information Gain (IG) was used to select a subset of features to provide significant information for separating NC and early-stage AD subjects. Based on the four modalities of the individual measures, i.e., sulcal measures, cortical thickness, cortical volume, subcortical volume, and combinations of these individual measures, three types of classifiers (Naïve Bayes, Logistic Regression and Support Vector Machine) were applied to compare the classification performances. We observed that sulcal measures were either superior than or equal to the other measures used for classification. Specifically, the g-SI and the width of the Sylvian fissure were two of the most sensitive sulcal measures and could be useful neuroanatomical markers for detecting early-stage AD. There were no significant differences between the three classifiers that we tested when using the same neuroanatomical features. PMID:28129351

  5. Outcomes in Patients With Early-Stage Hypopharyngeal Cancer Treated With Radiotherapy

    SciTech Connect

    Yoshimura, Ryo-ichi; Kagami, Yoshikazu; Ito, Yoshinori; Asai, Masao; Mayahara, Hiroshi; Sumi, Minako; Itami, Jun

    2010-07-15

    Purpose: To analyze the outcome in patients with early-stage hypopharyngeal cancer (HPC) who were treated with radiotherapy (RT). Methods and Materials: Between February 1988 and February 2007, 77 patients with Stage I or Stage II HPC underwent definitive RT in the Division of Radiation Oncology at the National Cancer Center Hospital. Eleven of the patients received local irradiation, and the other 66 patients received elective bilateral neck irradiation and booster irradiation to the primary lesion. The median follow-up period for all the patients was 33 months from the start of RT, ranging from 3 to 229 months. Results: The rates of overall survival, HPC-specific survival, HPC recurrence-free survival, and local control with laryngeal voice preservation for the 77 patients at 5 years were 47%, 74%, 57%, and 70%, respectively. The survival rates were not affected by the patient characteristics or treatment factors, but the RT field was significantly correlated with local control in a multivariate analysis. Seven of the patients had Grade 3 or greater complications, but these complications occurred after salvage surgery in 6 of the patients. Of the 77 patients, 83% had synchronous or metachronous malignancies, but these malignancies did not influence the survival of the patients if the malignancies were detected at an early stage. Conclusion: RT is an appropriate treatment method for early-stage HPC. However, because synchronous or metachronous malignancies occur at a relatively high frequency, careful follow-up and the early detection of such malignancies are critical.

  6. Minimally Invasive Surgery for Early-Stage Lung Cancer: From Innovation to Standard of Care.

    PubMed

    White, Abby; Swanson, Scott J

    2016-11-15

    The era of minimally invasive surgery for lung cancer follows decades of research; the collection and interpretation of countless qualitative and quantitative data points; and tireless efforts by a few pioneering thoracic surgeons who believed they could deliver a safe and oncologically sound operation with less tissue trauma, an improved physiologic profile, and fewer complications than traditional open surgery. This review highlights those efforts and the role of minimally invasive surgery for early-stage lung cancer in light of evolving technology, the emerging understanding of the biology of early-stage lung cancer, and lung cancer screening.

  7. Highly-accurate metabolomic detection of early-stage ovarian cancer

    PubMed Central

    Gaul, David A.; Mezencev, Roman; Long, Tran Q.; Jones, Christina M.; Benigno, Benedict B.; Gray, Alexander; Fernández, Facundo M.; McDonald, John F.

    2015-01-01

    High performance mass spectrometry was employed to interrogate the serum metabolome of early-stage ovarian cancer (OC) patients and age-matched control women. The resulting spectral features were used to establish a linear support vector machine (SVM) model of sixteen diagnostic metabolites that are able to identify early-stage OC with 100% accuracy in our patient cohort. The results provide evidence for the importance of lipid and fatty acid metabolism in OC and serve as the foundation of a clinically significant diagnostic test. PMID:26573008

  8. Effects of cigarette smoke exposure on early stage embryos in the rat

    SciTech Connect

    Tachi, Norihide; Aoyama, Mitsuko )

    1989-09-01

    It is well recognized that cigarette smoking in pregnant women exerts many deleterious effects on their progenies; intrauterine growth retardation, and increases in perinatal mortality and premature births. The fetal growth retardation also has been reported in animals exposed to cigarette smoke. The authors previously demonstrated that cigarette smoke exposure in pregnant rats retarded the growth of fetuses from mid to late stages of pregnancy. In addition, the weight of uteri containing embryos in animals inhaling the smoke was smaller, although not significant, than that in the control on day 7 of pregnancy. Based on these findings, it was suggested that the growth of embryos in early stage seemed to be harmfully affected as well as during mid and late stages of pregnancy. However, since the uterine weight in early pregnancy was measured in the previous study instead of the direct observation of early stage embryos, it remained unclear whether the early development of embryos was really influenced by cigarette smoke exposure or not. The present study was designed to observe the effects of cigarette smoke inhalation by pregnant rats on early development of embryos from fertilization to implantation.

  9. Haemoglobin degradation underpins the sensitivity of early ring stage Plasmodium falciparum to artemisinins

    PubMed Central

    Xie, Stanley C.; Dogovski, Con; Hanssen, Eric; Chiu, Francis; Yang, Tuo; Crespo, Maria P.; Stafford, Che; Batinovic, Steven; Teguh, Silvia; Charman, Susan; Klonis, Nectarios; Tilley, Leann

    2016-01-01

    ABSTRACT Current first-line artemisinin antimalarials are threatened by the emergence of resistant Plasmodium falciparum. Decreased sensitivity is evident in the initial (early ring) stage of intraerythrocytic development, meaning that it is crucial to understand the action of artemisinins at this stage. Here, we examined the roles of iron (Fe) ions and haem in artemisinin activation in early rings using Fe ion chelators and a specific haemoglobinase inhibitor (E64d). Quantitative modelling of the antagonism accounted for its complex dependence on the chemical features of the artemisinins and on the drug exposure time, and showed that almost all artemisinin activity in early rings (>80%) is due to haem-mediated activation. The surprising implication that haemoglobin uptake and digestion is active in early rings is supported by identification of active haemoglobinases (falcipains) at this stage. Genetic down-modulation of the expression of the two main cysteine protease haemoglobinases, falcipains 2 and 3, renders early ring stage parasites resistant to artemisinins. This confirms the important role of haemoglobin-degrading falcipains in artemisinin activation, and shows that changes in the rate of artemisinin activation could mediate high-level artemisinin resistance. PMID:26675237

  10. Confidence interval estimation of the difference between two sensitivities to the early disease stage.

    PubMed

    Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

    2014-03-01

    Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches.

  11. Modular IPS Machinery Arrangement in Early-Stage Naval Ship Design

    DTIC Science & Technology

    2013-04-01

    Modular IPS Machinery Arrangement in Early -Stage Naval Ship Design David J. Jurkiewicz1 Carderock Division Naval Surface Warfare Center West...design process as part of assessing system-level tradeoffs early within the ship design process. This paper describes a methodology for the...flexibility in the ship design since it is not necessary to align the propeller shaft with the prime movers . Instead, propulsion motors are coupled to the

  12. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA.

  13. Hydrodynamic instability of elastic-plastic solid plates at the early stage of acceleration

    NASA Astrophysics Data System (ADS)

    Piriz, A. R.; Sun, Y. B.; Tahir, N. A.

    2015-03-01

    A model is presented for the linear Rayleigh-Taylor instability taking place at the early stage of acceleration of an elastic-plastic solid, when the shock wave is still running into the solid and is driven by a time varying pressure on the interface. When the the shock is formed sufficiently close to the interface, this stage is considered to follow a previous initial phase controlled by the Ritchmyer-Meshkov instability that settles new initial conditions. The model reproduces the behavior of the instability observed in former numerical simulation results and provides a relatively simpler physical picture than the currently existing one for this stage of the instability evolution.

  14. Effects of temperature on survival and development of early life stage Pacific and western brook lampreys

    USGS Publications Warehouse

    Meeuwig, M.H.; Bayer, J.M.; Seelye, J.G.

    2005-01-01

    We examined the effects of temperature (10, 14, 18, and 22??C) on survival and development of Pacific lampreys Lampetra tridentata and western brook lampreys L. richardsoni during embryological and early larval stages. The temperature for zero development was estimated for each species, and the response to temperature was measured as the proportion of individuals surviving to hatch, surviving to the larval stage, and exhibiting abnormalities at the larval stage (i.e., malformations of the body). The estimated temperature for zero development was 4.850C for Pacific lampreys and 4.97??C for western brook lampreys. Survival was greatest at 18??C, followed by 14, 10, and 22??C, significant differences being observed between 22??C and the other temperatures. Overall survival was significantly greater for western brook lampreys than for Pacific lampreys; however, the overall difference in proportion of individuals surviving was only 0.02. Overall survival significantly decreased from the time of hatch (proportion surviving = 0.85) to the larval stage (0.82; i.e., during the free-embryo stage). The proportion of individuals exhibiting abnormalities at the larval stage was greatest at 22??C, followed by 18, 10, and 14??C, significant differences being observed between 22??C and the other temperatures. These data provide baseline information on the thermal requirements of early life stage Pacific and western brook lampreys and will aid in assessment and prediction of suitable spawning and rearing habitats for these species.

  15. Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages

    USGS Publications Warehouse

    DeBoer, Jason A.; Pope, Kevin L.

    2015-01-01

    Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age-0 larval’; age 0 during autumn: ‘age-0 juvenile’; and age 1 during autumn: ‘age-1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age-0 larval, age-0 juvenile and age-1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage-specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year-class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.

  16. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  17. Sensitivity of early life stages of white sturgeon, rainbow trout, and fathead minnow to copper.

    PubMed

    Vardy, David W; Oellers, Johanna; Doering, Jon A; Hollert, Henner; Giesy, John P; Hecker, Markus

    2013-01-01

    Populations of white sturgeon (WS; Acipenser transmontanus) are in decline in several parts of the United States and Canada, attributed primarily to poor recruitment caused by degradation of habitats, including pollution with contaminants such as metals. Little is known about sensitivity of WS to contaminants or metals such as copper (Cu). Here, acute (96 h) mortalities of WS early life stages due to exposure to Cu under laboratory conditions are reported. Two standard test species, rainbow trout (Oncorhynchus mykiss) and fathead minnow (Pimephales promelas), were exposed in parallel to determine relative sensitivity among species. Swim-up larvae [15 days post-hatch (dph)] and early juveniles (40-45 dph) of WS were more sensitive to Cu (LC(50) = 10 and 9-17 μg/L, respectively) than were yolksac larvae (8 dph; LC(50) = 22 μg/L) and the later juvenile life stage (100 dph; LC(50) = 54 μg/L). WS were more sensitive to Cu than rainbow trout and fathead minnow at all comparable life stages tested. Yolksac larvae of rainbow trout and fathead minnow were 1.8 and 4.6 times, respectively, more tolerant than WS, while swim-up and juvenile life stages of rainbow trout were between 1.4- and 2.4-times more tolerant than WS. When plotted in a species sensitivity distribution with other fishes, the mean acute toxicity value for early life stage WS was ranked between the 1st and 2nd centile. The WS life stage of greatest Cu sensitivity coincides with the beginning of active feeding and close association with sediment, possibly increasing risk. WS early life stages are sensitive to aqueous copper exposure and site-specific water quality guidelines and criteria should be evaluated closely to ensure adequate protection.

  18. Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

    PubMed

    Heusinkveld, Lauren; Hacker, Mallory; Turchan, Maxim; Bollig, Madelyn; Tamargo, Christina; Fisher, William; McLaughlin, Lauren; Martig, Adria; Charles, David

    2017-01-01

    The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

  19. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    USGS Publications Warehouse

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  20. Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

    SciTech Connect

    Calais, G.; Le Floch, O.; Chauvet, B.; Reynaud-Bougnoux, A.; Bougnoux, P. )

    1989-12-01

    In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor.

  1. "It's the Bread and Butter of Our Practice": Experiencing the Early Years Foundation Stage

    ERIC Educational Resources Information Center

    Roberts-Holmes, Guy

    2012-01-01

    This article presents the experiences of nursery and primary head teachers (n = 12) on the English Early Years Foundation Stage (EYFS) after its first year of implementation in 2010. Findings are drawn from a subset of data (head teachers of primary and nursery schools) which forms part of a larger Department for Children, Schools and Families…

  2. Alternatives to Mechanical Drills for the Early Stages of Language Practice in Foreign Language Textbooks

    ERIC Educational Resources Information Center

    Aski, Janice M.

    2005-01-01

    There is a growing body of research indicating that mechanical drills do not facilitate the development of explicit or implicit knowledge. This study identifies the inadequate aspects of mechanical drills and offers alternative activities for the early stages of language practice, whose formats and features comply with recent research in the…

  3. Memory Club: A Group Intervention for People with Early-Stage Dementia and Their Care Partners

    ERIC Educational Resources Information Center

    Zarit, Steven H.; Femia, Elia E.; Watson, Jennifer; Rice-Oeschger, Laura; Kakos, Bernadette

    2004-01-01

    Purpose: Diagnosis of dementia in its early stages presents a window of opportunity for examining the immediate and long-term consequences of the illness at a point when the individual with memory loss can still participate in decision making. Design and Methods: Memory Club is a l0-session group program designed to provide information about…

  4. Test Design Optimization in CAT Early Stage with the Nominal Response Model

    ERIC Educational Resources Information Center

    Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

    2007-01-01

    The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

  5. Treatment of Early-Stage Pressure Ulcers by Using Autologous Adipose Tissue Grafts

    PubMed Central

    Marangi, Giovanni Francesco; Pallara, Tiziano; Cagli, Barbara; Schena, Emiliano; Giurazza, Francesco; Faiella, Elio; Zobel, Bruno Beomonte; Persichetti, Paolo

    2014-01-01

    Assessing pressure ulcers (PUs) in early stages allows patients to receive safer treatment. Up to now, in addition to clinical evaluation, ultrasonography seems to be the most suitable technique to achieve this goal. Several treatments are applied to prevent ulcer progression but none of them is totally effective. Furthermore, the in-depth knowledge of fat regenerative properties has led to a wide use of it. With this study the authors aim at introducing a new approach to cure and prevent the worsening of early-stage PUs by using fat grafts. The authors selected 42 patients who showed clinical and ultrasonographic evidence of early-stage PUs. Values of skin thickness, fascial integrity, and subcutaneous vascularity were recorded both on the PU area and the healthy trochanteric one, used as control region. Fat grafting was performed on all patients. At three months, abnormal ultrasonographic findings, such as reduction of cutaneous and subcutaneous thickness, discontinuous fascia, and decrease in subcutaneous vascularity, all were modified with respect to almost all the corresponding parameters of the control region. Results highlight that the use of fat grafts proved to be an effective treatment for early-stage PUs, especially in the care of neurological and chronic bedridden patients. PMID:24818019

  6. Implementation of the TMS in the early stages of Parkinson's disease.

    PubMed

    Guekht, A; Selikhova, M; Serkin, G; Gusev, E

    2005-01-01

    47 PD patients were investigated with the single-pulse TMS to find out changes in motor evoked potential and motor conduction related to the stage of minimal motor symptoms and its further deterioration in groups with the different clinical types of the disease. The investigation revealed a markedly longer MEP duration along with the increased number of phases, than in controls, which were bilateral and advanced despite the minimal unilateral motor symptoms. There was also increased MEP amplitude in facilitation, with a higher degree of asymmetry, compared to controls. Patients with predominant rigid clinical forms had the further MEP duration and amplitude increase proportionally to bradikinesia and rigidity in the early stages of the disease. Patients with tremor predominant forms had no further changes in the MEP duration and amplitude, but had their motor CCT decreased in the early stages. Patients with the akinetic form were characterized by the asymmetric increase in the MEP Amplitude in relaxation and motor CCT shortening. Thus, TMS allows us to diagnose early the possible central motor changes secondary to Parkinson's disease, reveals the difference in compensational capacity according to the clinical type of the disease and helps in monitoring of the severity of motor changes in early stages.

  7. Sydney, Australia Community Meets Classroom: Celebrating Families and Difference in the Early Stages of Primary Education

    ERIC Educational Resources Information Center

    Burns, Kellie

    2006-01-01

    Teachers and teacher educators are often hard pressed to find resources that creatively integrate lesbian, gay, bisexual, transgender (LGBT), and intersex issues into the early stages of primary education. While there is a growing number of academics who stress the importance of addressing topics of sexual and gender diversity during the early…

  8. Arthroscopic core decompression of the lunate in early stage Kienbock disease of the lunate.

    PubMed

    Bain, Gregory I; Smith, Michael L; Watts, Adam C

    2011-03-01

    Since the first description of Kienbock disease in 1910, the etiology and treatment have remained controversial topics. Core decompression is an accepted treatment option in early-stage avascular necrosis of the femoral head, and more recently the humeral head. This paper reports the technique of arthroscopic fluoroscopically guided core decompression of the lunate with 6-year results.

  9. 77 FR 74908 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-18

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Small Business Investment Companies--Early Stage SBICs AGENCY: U.S. Small Business Administration... managers to submit the preliminary materials discussed in Section II, in the form of the Small...

  10. Early-Stage Chunking of Finger Tapping Sequences by Persons Who Stutter and Fluent Speakers

    ERIC Educational Resources Information Center

    Smits-Bandstra, Sarah; De Nil, Luc F.

    2013-01-01

    This research note explored the hypothesis that chunking differences underlie the slow finger-tap sequencing performance reported in the literature for persons who stutter (PWS) relative to fluent speakers (PNS). Early-stage chunking was defined as an immediate and spontaneous tendency to organize a long sequence into pauses, for motor planning,…

  11. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  12. Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...

  13. Fish early life stage: Developing AOPs to support targeted reduction and replacement

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

  14. 13 CFR 107.1182 - Valuation requirements for Early Stage SBICs based on Capital Impairment Percentage.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1182 Valuation... designated by SBA. Conditional Commitments by SBA To Reserve Leverage for a Licensee...

  15. 13 CFR 107.1182 - Valuation requirements for Early Stage SBICs based on Capital Impairment Percentage.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1182 Valuation... designated by SBA. Conditional Commitments by SBA To Reserve Leverage for a Licensee...

  16. Communication in the Early Stage of Language Development in Children with CHARGE Syndrome

    ERIC Educational Resources Information Center

    Peltokorpi, Sini; Huttunen, Kerttu

    2008-01-01

    CHARGE syndrome is characterized by multiple physical abnormalities, and impaired vision and hearing. In this pilot study, communication in the early stage of language development in three one- to eight-year-old children with CHARGE syndrome was explored using video recorded free-play interaction sessions and a parental questionnaire. The children…

  17. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    ERIC Educational Resources Information Center

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  18. Association Between Increased Vascular Density and Loss of Protective RAS in Early-stage NPDR

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2016-01-01

    Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The renin-angiotensin system (RAS) is implicated in the pathogenesis of DR and in the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population that is instrumental in vascular repair.

  19. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  20. 76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage SBICs; Public Webinars AGENCY: U.S. Small Business Administration. ACTION: Notice of public Webinars. SUMMARY: The U.S. Small Business Administration (SBA) announces that it is holding a series of public Webinars regarding...

  1. Responding to the Challenges of Active Citizenship through the Revised UK Early Years Foundation Stage Curriculum

    ERIC Educational Resources Information Center

    Baker, Fiona S.

    2013-01-01

    The revised UK Early Years Foundation Stage (EYFS) now places a stronger emphasis on personal, social and emotional development (PSED) as one of its three prime areas. PSED has three characteristics of learning: active learning, creating and thinking critically, and playing and exploring. These aspects of the revised EYFS closely align with the…

  2. Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

    ERIC Educational Resources Information Center

    Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

    2014-01-01

    Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

  3. Perinatal Risks Associated with Early Vanishing Twin Syndrome following Transfer of Cleavage- or Blastocyst-Stage Embryos

    PubMed Central

    Pryor, Katherine P.; Petrini, Allison C.; Lekovich, Jovana P.; Stahl, Jaclyn; Elias, Rony T.; Spandorfer, Steven D.

    2016-01-01

    Objective. To investigate whether the perinatal risks associated with early vanishing twin (VT) syndrome differ between cleavage- or blastocyst-stage embryo transfers (ET) in fresh in vitro fertilization (IVF) cycles. Methods. Retrospective, single-center, cohort study of IVF cycles with fresh cleavage- or blastocyst-stage ETs resulting in a live singleton birth. The incidence of preterm birth (PTB), low birth weight (LBW), and very low birth weight (VLBW) was compared between cleavage- and blastocyst-stage ET cycles complicated by early VT. Results. 7241 patients had live singleton births. Early VT was observed in 709/6134 (11.6%) and 70/1107 (6.32%) patients undergoing cleavage-stage and blastocyst-stage ETs, respectively. Patients in the blastocyst-stage group were younger compared to the cleavage-stage group. The cleavage-stage group had a similar birth weight compared to the blastocyst-stage group. There was no difference in the incidence of PTB (9.87% versus 8.57%), LBW (11.1% versus 11.4%), or VLBW (1.13 versus 1.43%) when comparing the cleavage-stage early VT and blastocyst-stage early VT groups, even after adjustment with logistic regression. Conclusions. Our study highlights that the adverse perinatal risks of PTB, LBW, and VLBW associated with early VT syndrome are similar in patients undergoing cleavage-stage or blastocyst-stage ETs during fresh IVF cycles. PMID:28101380

  4. Following iron speciation in the early stages of magnetite magnetosome biomineralization

    SciTech Connect

    Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; Faivre, Damien; Prozorov, Tanya

    2016-02-26

    Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structure with a majority of iron present as Fe3+ and trace amounts of Fe2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.

  5. The δ-cyclin expression at early stages of embryogenesis of Brassica rapa L. under clinorotation

    NASA Astrophysics Data System (ADS)

    Artemenko, O. A.; Popova, A. F.

    We present some results of comparison studying of Brassica embryo development and the δ-cyclin genes expression under slow horizontal clinorotation and in the laboratory control. Some backlog of the δ1-cyclin genes expression at early stages of embryogenesis under clinorotation was revealed in comparison with the laboratory control. The similar level of the δ3-cyclin expression at all stages of embryo formation (from one to nine days) in both variants is shown. Some delays in the rate of Brassica rapa embryo development under clinorotation in comparison with the laboratory control can be a result of decrease of a level and some backlog of the δ1-cyclin expression at early stages of embryogenesis.

  6. Following iron speciation in the early stages of magnetite magnetosome biomineralization

    DOE PAGES

    Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; ...

    2016-02-26

    Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structure withmore » a majority of iron present as Fe3+ and trace amounts of Fe2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.« less

  7. Aquaporin expression in the cerebral cortex is increased at early stages of Alzheimer disease.

    PubMed

    Pérez, Esther; Barrachina, Marta; Rodríguez, Agustín; Torrejón-Escribano, Benjamín; Boada, Mercé; Hernández, Isabel; Sánchez, Marisa; Ferrer, Isidre

    2007-01-12

    Abnormalities in the cerebral microvasculature are common in Alzheimer disease (AD). Expression levels of the water channels aquaporin 1 and aquaporin 4 (AQP1, AQP4) were examined in AD cases by gel electrophoresis and Western blotting, and densitometric values normalized with beta-actin were compared with corresponding values in age-matched controls processed in parallel. In addition, samples of cases with Pick disease (PiD) were examined for comparative purposes. A significant increase in the expression levels of AQP1 was observed in AD stage II (following Braak and Braak classification). Individual variations were seen in advanced stages which resulted in non-significant differences between AD stages V-VI and age-matched controls. No differences in AQP1 levels were observed between familial AD cases (FAD, all of them at advanced stages) and corresponding age-matched controls. Immunohistochemistry showed increased AQP1 in astrocytes at early stages of AD. Double-labelling immunofluorescence and confocal microscopy disclosed AQP1 immunoreactivity at the cell surface of astrocytes which were recognized with anti-glial fibrillary acidic protein antibodies. No differences in the levels of AQP4 were observed in AD, FAD and PiD when compared with corresponding controls. These results indicate abnormal expression of AQP1 in astrocytes in AD, and they add support to the idea that abnormal regulation of mechanisms involved in the control of water fluxes occurs at early stages in AD.

  8. Apathy in untreated early-stage Parkinson disease: relationship with other non-motor symptoms.

    PubMed

    Dujardin, Kathy; Langlois, Carole; Plomhause, Lucie; Carette, Anne-Sophie; Delliaux, Marie; Duhamel, Alain; Defebvre, Luc

    2014-12-01

    Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment-naive patients with early-stage PD has not been extensively investigated. Moreover, whether apathy is related to other non-motor symptoms in early-stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment-naive patients with early-stage PD. Ninety-five treatment-naive patients with early-stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non-apathetic patients. When considering non-motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non-apathetic patients. In treatment-naive patients with early-stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anhedonia.

  9. Early stages of probable Alzheimer disease are associated with changes in platelet amyloid precursor protein forms.

    PubMed

    Borroni, B; Colciaghi, F; Corsini, P; Akkawi, N; Rozzini, L; Del Zotto, E; Talarico, G; Cattabeni, F; Lenzi, G L; Di Luca, M; Padovani, A

    2002-12-01

    Previous findings demonstrated an altered pattern of amyloid precursor protein (APP) forms in platelets of Alzheimer disease (AD) patients, compared both with healthy control subjects or patients with non-Alzheimer-type dementia. The present study aims to evaluate whether platelet APP form ratio (APPr) is altered in patients with early stage AD. We selected 40 patients with early stage AD and 40 age-matched healthy controls. Compared with controls (mean+/-SD=0.91+/-0.3), mean APPr was decreased in AD (mean+/-SD=0.46+/-0.26, p<0.0001). Sixteen very mild AD patients (clinical dementia rating=0.5), identified among the AD group, showed a significant decrease of APPr values (mean+/-SD=0.50+/-0.3, p<0.0001). These findings indicate that alteration of APP processing in platelets is an early event and suggest that this assay might be of diagnostic value in differentiating mild AD from normal ageing.

  10. Effects of prometryne on early life stages of common carp (Cyprinus carpio L.).

    PubMed

    Velisek, Josef; Stara, Alzbeta; Koutnik, Dalibor; Machova, Jana

    2015-02-01

    Toxicity of prometryne to early life stages of common carp was assessed. On the basis of accumulated mortality in the experimental groups lowest observed-effect concentration (LOEC) was estimated as 1100 µg/l; and no observed-effect concentration (NOEC) was 850 µg/l. Fulton's condition factor was significantly lower than in controls in fish exposed to 4000 µg/l after 7, 14, and 21 days. By day 14, fish exposed to 4000 µg/l prometryne showed significantly lower mass and total length compared to controls. Fish exposed the 1200 and 4000 µg/l showed delay in development, severe hyperaemia in gill, liver, and caudal and cranial kidney. Subchronic prometryne exposure of early-life stages of common carp at concentrations of 1200 and 4000 µg/l affected their survival, growth rate, early ontogeny, and histology.

  11. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

    2016-03-01

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

  12. Early developmental stages of Ascaris lumbricoides featured by high-resolution mass spectrometry.

    PubMed

    Melo, Carlos Fernando Odir Rodrigues; Esteves, Cibele Zanardi; de Oliveira, Rosimeire Nunes; Guerreiro, Tatiane Melina; de Oliveira, Diogo Noin; Lima, Estela de Oliveira; Miné, Júlio César; Allegretti, Silmara Marques; Catharino, Rodrigo Ramos

    2016-11-01

    Ascaris lumbricoides is responsible for a highly disseminated helminth parasitic disease, ascariosis, a relevant parasitosis that responds for great financial burden on the public health system of developing countries. In this work, metabolic fingerprinting using high-resolution mass spectrometry (HRMS) was employed to identify marker molecules from A. lumbricoides in different development stages. We have identified nine biomarkers, such as pheromones and steroidal prohormones in early stages, among other molecules in late development stages, making up four molecules for fertilized eggs, four marker molecules for first larvae (L1) and one marker molecule for third larvae (L3). Therefore, our findings indicate that this approach is suitable for biochemical characterization of A. lumbricoides development stages. Moreover, the straightforward analytical method employed, with almost no sample preparation from a complex matrix (feces) using high-resolution mass spectrometry, suggests that it is possible to seek for an easier and faster way to study animal molding processes.

  13. Astronomical Constraints on the Duration of Early Jurassic Stages and Global Carbon Cycle and Climatic Perturbations

    NASA Astrophysics Data System (ADS)

    Ruhl, M.; Hesselbo, S. P.; Hinnov, L.; Jenkyns, H. C.; Storm, M.; Xu, W.; Riding, J. B.; Ullmann, C. V.

    2015-12-01

    The Early Jurassic (201.3 to 174.1 Ma) is bracketed by the end-Triassic mass extinction and global warming event, and the Toarcian-Aalenian shift to (global) icehouse conditions (McElwain et al., 1999; Hesselbo et al., 2002; Ruhl et al., 2011; Korte et al., in review). It is further marked by the early Toarcian Oceanic Anoxic Event (T-OAE), with possibly the largest exogenic carbon cycle perturbation of the Mesozoic and related perturbations in global geochemical cycles, climate and the environment, which are linked to large igneous province emplacement in the Karoo-Ferrar region (Jenkyns, 2010; Burgess et al., 2015). Furthermore, Early Jurassic continental rifting and the break-up of Pangaea and subsequent Early Jurassic opening of the Hispanic Corridor and Viking Strait respectively linked the equatorial Tethys Ocean to Eastern Panthalassa and the high-latitude Arctic Boreal realm. This initiated changes in (global) ocean currents and Earth's heat distribution and ultimately was followed by the opening of the proto-North Atlantic (Porter et al., 2013; Korte et al., in review). Here, we present high-resolution (sub-precession scale) elemental concentration data from the Mochras borehole (UK), which represents ~1300m of possibly the most complete and expanded lower Jurassic hemi-pelagic marine sedimentary archive known. We construct a floating ~9 Myr astronomical time-scale for the complete Early Jurassic Pliensbachian stage and biozones. Combined with radiometric and astrochronological constraints on early Jurassic stage boundaries, we construct a new Early Jurassic Time-Scale. With this we assess the duration and rate of change of early Jurassic global carbon cycle and climatic perturbations and we asses fundamental changes in the nature and expression of Early Jurassic long (100 - 1000 kyr) eccentricity cycles.

  14. Characterization of early stage cartilage degradation using diffuse reflectance near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Brown, C. P.; Jayadev, C.; Glyn-Jones, S.; Carr, A. J.; Murray, D. W.; Price, A. J.; Gill, H. S.

    2011-04-01

    Interest in localized and early stage treatment technologies for joint conditions such as osteoarthritis is growing rapidly. It has therefore become important to develop objective measures capable of characterizing the earliest (non-visible) changes associated with degeneration to aid treatment procedures. In addition to assessing tissue before treatment, it is further important to develop an effective, non-destructive means of monitoring post-treatment tissue healing, and of providing the high-quality data needed for trials of developing treatment methods. To investigate its ability to detect the early stages of degeneration in cartilage-on-bone, diffuse reflectance near infrared spectroscopy was applied to normal and osteoarthritic joints. A discriminating function was developed to relate absorbance peaks of interest and track degradation around focal osteoarthritic defects. The function could distinguish between normal and degraded tissue (100% separation of normal tissue from that within 25 mm of a defect) and between different stages of osteoarthritic progression (p < 0.05). This technique allows simple, practical and non-destructive assessment of component-level properties over the full depth of the tissue. It has the potential to increase our understanding of the underlying etiologic and pathogenic processes in early stage degeneration, to assist classification and the development of new treatment methods.

  15. Expression Analysis of Cathepsin F during Embryogenesis and Early Developmental Stage in Olive Flounder (Paralichthys olivaceus)

    PubMed Central

    Lee, Jang-Wook; Lee, Young Mee; Yang, Hyun; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Hwang, In Joon; Kim, Sung Yeon; Lee, Jeong-Ho

    2013-01-01

    Cathepsins are members of the multigene family of lysosomal cysteine proteinases and have regulated function in several life processes. The potential role of cathepsin F cysteine gene was expected as protease in the yolk processing mechanism during early developmental stage, but expression analysis was unknown after fertilization. The alignment analysis showed that amino acid sequence of cathepsin F from olive flounder liver expressed sequence tag (EST) homologous to cathepsin F of other known cathepsin F sequences with 87-98% identity. In this study, we examined the gene expression analysis of cathepsin F in various tissues at variety age flounder. Tissue distribution of the cathepsin F mRNA has been shown to be ubiquitous and constitutive pattern regardless of age in each group, although derived from cDNA library using liver sample. The mRNA level of cathepsin F more increased as developmental proceed during embryogenesis and early developmental stage, especially increased in the blastula, hatching stage and 3 days post hatching (dph). As a result, it may suggest that the proteolysis of yolk proteins (YPs) has been implicated as a mechanism for nutrient supply during early larval stages in olive flounder. PMID:25949137

  16. Complexity of resting-state EEG activity in the patients with early-stage Parkinson's disease.

    PubMed

    Yi, Guo-Sheng; Wang, Jiang; Deng, Bin; Wei, Xi-Le

    2017-04-01

    To investigate the abnormal brain activities in the early stage of Parkinson's disease (PD), the electroencephalogram (EEG) signals were recorded with 20 channels from non-dementia PD patients (18 patients, 8 females) and age matched healthy controls (18 subjects, 8 females) during the resting state. Two methods based on the ordinal patterns of the recorded series, i.e., permutation entropy (PE) and order index (OI), were introduced to characterize the complexity of the cortical activities for two groups. It was observed that the resting-state EEG of PD patients showed lower PE and higher OI than healthy controls, which indicated that the early-stage PD caused the reduced complexity of EEG. We further applied two methods to determine the complexity of EEG rhythms in five sub-bands. The results showed that the gamma, beta and alpha rhythms of PD patients were characterized by lower PE and higher OI, i.e., reduced complexity, than healthy subjects. No significant differences were observed in theta or delta rhythms between two groups. The findings suggested that PE and OI were promising methods to detect the abnormal changes in the dynamics of EEG signals associated with early-stage PD. Further, such changes in EEG complexity may be the early markers of the cortical or subcortical dysfunction caused by PD.

  17. Rehabilitation outcomes in patients with early and two-stage reconstruction of flexor tendon injuries

    PubMed Central

    Sade, Ilgin; İnanir, Murat; Şen, Suzan; Çakmak, Esra; Kablanoğlu, Serkan; Selçuk, Barin; Dursun, Nigar

    2016-01-01

    [Purpose] The primary aim of this study was to assess rehabilitation outcomes for early and two-stage repair of hand flexor tendon injuries. The secondary purpose of this study was to compare the findings between treatment groups. [Subjects and Methods] Twenty-three patients were included in this study. Early repair (n=14) and two-stage repair (n=9) groups were included in a rehabilitation program that used hand splints. This retrospective evaluated patients according to their demographic characteristics, including age, gender, injured hand, dominant hand, cause of injury, zone of injury, number of affected fingers, and accompanying injuries. Pain, range of motion, and grip strength were evaluated using a visual analog scale, goniometer, and dynamometer, respectively. [Results] Both groups showed significant improvements in pain and finger flexion after treatment compared with baseline measurements. However, no significant differences were observed between the two treatment groups. Similar results were obtained for grip strength and pinch grip, whereas gross grip was better in the early tendon repair group. [Conclusion] Early and two-stage reconstruction of patients with flexor tendon injuries can be performed with similarly favorable responses and effective rehabilitation programs. PMID:27630400

  18. The Neuroprotective Effects of Carnosine in Early Stage of Focal Ischemia Rodent Model

    PubMed Central

    Park, Hui-Seung; Han, Kyung-Hoon; Shin, Jeoung-A; Park, Joo-Hyun; Song, Kwan-Young

    2014-01-01

    Objective This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke. PMID:24851146

  19. Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

    PubMed Central

    Bhalla, Sherry; Chaudhary, Kumardeep; Kumar, Ritesh; Sehgal, Manika; Kaur, Harpreet; Sharma, Suresh; Raghava, Gajendra P. S.

    2017-01-01

    In this study, an attempt has been made to identify expression-based gene biomarkers that can discriminate early and late stage of clear cell renal cell carcinoma (ccRCC) patients. We have analyzed the gene expression of 523 samples to identify genes that are differentially expressed in the early and late stage of ccRCC. First, a threshold-based method has been developed, which attained a maximum accuracy of 71.12% with ROC 0.67 using single gene NR3C2. To improve the performance of threshold-based method, we combined two or more genes and achieved maximum accuracy of 70.19% with ROC of 0.74 using eight genes on the validation dataset. These eight genes include four underexpressed (NR3C2, ENAM, DNASE1L3, FRMPD2) and four overexpressed (PLEKHA9, MAP6D1, SMPD4, C11orf73) genes in the late stage of ccRCC. Second, models were developed using state-of-art techniques and achieved maximum accuracy of 72.64% and 0.81 ROC using 64 genes on validation dataset. Similar accuracy was obtained on 38 genes selected from subset of genes, involved in cancer hallmark biological processes. Our analysis further implied a need to develop gender-specific models for stage classification. A web server, CancerCSP, has been developed to predict stage of ccRCC using gene expression data derived from RNAseq experiments. PMID:28349958

  20. Transcriptome profile of the early stages of breast cancer tumoral spheroids

    PubMed Central

    Pacheco-Marín, Rosario; Melendez-Zajgla, Jorge; Castillo-Rojas, Gonzalo; Mandujano-Tinoco, Edna; Garcia-Venzor, Alfredo; Uribe-Carvajal, Salvador; Cabrera-Orefice, Alfredo; Gonzalez-Torres, Carolina; Gaytan-Cervantes, Javier; Mitre-Aguilar, Irma B.; Maldonado, Vilma

    2016-01-01

    Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to reliably mimic the initial growth of primary and metastatic cancer cells. However, cancer cell growth during the initial stages has not been fully explored using a genome-wide approach. Thus, in the present study, we investigated the transcriptome of breast cancer cells during the initial stages of tumoral growth using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses showed that a metastatic signature was enriched as several adhesion molecules were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which were further supported by an increase in cell migration. Interestingly, we also found that the cancer cells at this stage of growth exhibited a paradoxical hyperactivation of oxidative mitochondrial metabolism. In addition, we found a large number of regulated (long non coding RNA) lncRNAs, several of which were co-regulated with neighboring genes. The regulatory role of some of these lncRNAs on mRNA expression was demonstrated with gain of function assays. This is the first report of an early-stage MTS transcriptome, which not only reveals a complex expression landscape, but points toward an important contribution of long non-coding RNAs in the final phenotype of three-dimensional cellular models. PMID:27021602

  1. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    PubMed

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  2. Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells

    SciTech Connect

    Hong, Dun; Chen, Hai-Xiao; Yu, Hai-Qiang; Liang, Yong; Wang, Carrie; Lian, Qing-Quan; Deng, Hai-Teng; Ge, Ren-Shan

    2010-08-15

    Bone remodeling relies on a dynamic balance between bone formation and resorption, mediated by osteoblasts and osteoclasts, respectively. Under certain stimuli, osteoprogenitor cells may differentiate into premature osteoblasts and further into mature osteoblasts. This process is marked by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. In this study, we induced osteoblast differentiation in mouse osteoprogenitor MC3T3-E1 cells and divided the process into three stages. In the first stage (day 3), the MC3T3-E1 cell under osteoblast differentiation did not express ALP or deposit a mineralized nodule. In the second stage, the MC3T3-E1 cell expressed ALP but did not form a mineralized nodule. In the third stage, the MC3T3-E1 cell had ALP activity and formed mineralized nodules. In the present study, we focused on morphological and proteomic changes of MC3T3-E1 cells in the early stage of osteoblast differentiation - a period when premature osteoblasts transform into mature osteoblasts. We found that mean cell area and mean stress fiber density were increased in this stage due to enhanced cell spreading and decreased cell proliferation. We further analyzed the proteins in the signaling pathway of regulation of the cytoskeleton using a proteomic approach and found upregulation of IQGAP1, gelsolin, moesin, radixin, and Cfl1. After analyzing the focal adhesion signaling pathway, we found the upregulation of FLNA, LAMA1, LAMA5, COL1A1, COL3A1, COL4A6, and COL5A2 as well as the downregulation of COL4A1, COL4A2, and COL4A4. In conclusion, the signaling pathway of regulation of the cytoskeleton and focal adhesion play critical roles in regulating cell spreading and actin skeleton formation in the early stage of osteoblast differentiation.

  3. Notch and Delta mRNAs in early-stage and mid-stage Drosophila embryos exhibit complementary patterns of protein producing potentials

    PubMed Central

    Shepherd, Andrew; Wesley, Uma; Wesley, Cedric

    2010-01-01

    Notch and Delta proteins generate Notch signaling that specifies cell fates during animal development. There is an intriguing phenomenon in Drosophila embryogenesis that has not received much attention and whose significance to embryogenesis is unknown. Notch and Delta mRNAs expressed in early-stage embryos are shorter than their counterparts in mid-stage embryos. We show here that the difference in sizes is due to mRNA 3′ processing at alternate polyadenylation sites. While the early-stage Notch mRNA has a lower protein-producing potential than the mid-stage Notch mRNA, the early-stage Delta mRNA has a higher protein-producing potential than the mid-stage Delta mRNA. Our data can explain the complementary patterns of Notch and Delta protein levels in early-stage and mid-stage embryos. Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3′ UTR and mRNA 3′ processing factors. PMID:20201103

  4. [Comparative proteome analysis of blood plasma of patients with early-stage chronic cerebral ischemia].

    PubMed

    Kisrieva, Y S; Petushkova, N A; Samenkova, N F; Kuznetsova, G P; Larina, O V; Zavialova, M G; Teryaeva, N B; Belyaev, A Y; Karuzina, I I

    2016-07-01

    In the present study, we explored the technology of liquid chromatography-mass spectrometry (HPLC-MS/MS) for the proteome analysis of blood plasma of patients with early chronic cerebral ischemia. Analysis of mass-spectrometer data carried out in automatic mode using the software Progenesis LS-MS. As a result of this study identified 43 proteins. The differences identified in the study group compared with the control in 7 proteins. It was found that in the early stages of chronic cerebral ischemia proteome changes in blood plasma affect proteins related to the immune system, the system for the maintenance of hemostasis and lipid metabolism.

  5. A functional account of verb use in the early stages of English multiword development.

    PubMed

    Cameron-Faulkner, Thea

    2012-09-01

    The present study investigates flexibility of verb use in the early stages of English multiword development, and its relationship with patterns attested in the input. The data is taken from a case study of a monolingual English-speaking boy aged 2 ; 5-2 ; 9 and his mother while engaged in daily activities in the home. Data were coded according to Halliday's (1975) functional system. The findings suggest that early multiword verb use is functionally restricted and closely tied to verb use in the input.

  6. Early stages of development of the Taenia solium metacestode in pigs.

    PubMed

    Garrido, Gerardo Salas; de Aluja, Aline S; Casas, Fernando Constantino

    2007-04-01

    In order to identify the early stages of Taenia solium metacestodes, 12 pigs were each fed 100,000 viable eggs and later killed and necropsied at different times after infection. Hematoxylin-eosin (HE) and immunohistochemical techniques (IHCs) were used to identify onchospheres and cysticerci in different tissues. At 2 days postinfection (dpi) structures compatible with onchospheres were found in the lumen of the small intestine, and in the mesenteric blood vessels and lymph nodes. At 4 dpi, these same structures were observed in the small intestine, the liver, and skeletal muscles. Between 6 and 39 dpi, they were found only in skeletal muscles. Between 2 and 6 dpi the postonchospheres were circular and oval shaped and measured between 6 and 34 x 27 microm. From 14 to 39 dpi, well-developed metacestodes 550 x 750 microm were observed. IHCs support the identification of early stages of T. solium.

  7. Early Stages of De Novo Designed Beta-Hairpin Peptide Self-Assembly

    NASA Astrophysics Data System (ADS)

    Yucel, Tuna; Schneider, Joel P.; Pochan, Darrin J.

    2007-03-01

    In aqueous solution, MAX 1 peptide is unfolded and does not self-assemble. The peptide intramolecularly folds into a beta-hairpin when the electrostatic interactions between charged residues are screened through increasing the ionic strength at neutral pH. Beta-hairpin molecules supramolecularly assemble via hydrophobic collapse and hydrogen bonding into a 3-D hydrogel network. By combining the results of CD, cryo-TEM, DLS, and oscillatory rheology, we understand that the self-assembly proceeds by nucleation of monodisperse (3 nm wide) beta-sheet fibrils, which elongate, branch and cross-link to form clusters of fibrils. Assembly kinetics at this early stage indicates power law growth with assembly time. Eventually, clusters of fibrils interpenetrate to form a percolated network, as evidenced by the increasing network rigidity. The early stage assembly process will be discussed and compared to published gelation models.

  8. Turning visual shapes into sounds: early stages of reading acquisition revealed in the ventral occipitotemporal cortex.

    PubMed

    Perrone-Bertolotti, M; Vidal, J R; de Palma, L; Hamamé, C M; Ossandon, T; Kahane, P; Minotti, L; Bertrand, O; Lachaux, J-P

    2014-04-15

    The exact role of the left ventral occipitotemporal cortex (VOTC) during the initial stages of reading acquisition is a hotly debated issue, especially regarding the comparative effect of learning on early stimulus-dependent vs. later task-dependent processes. We show that this controversy can be solved with high-temporal resolution intracerebral EEG recordings of the VOTC. We measured High-Frequency Activity (50-150 Hz) as a proxy of population-level spiking activity while participants learned Japanese Katakana symbols, and found that learning primarily affects top-down/task-dependent neural processing, after a few minutes only. In contrast, adaptation of early bottom-up/stimulus-dependent processing takes several days to adapt and provides the basis for fluent reading. Such evidence that two consecutive stages of neural processing, stimulus- and task-dependent are differentially affected by learning, can reconcile seemingly opposite hypotheses on the role of the VOTC during reading acquisition.

  9. Nerve growth factor regulates axial rotation during early stages of chick embryo development.

    PubMed

    Manca, Annalisa; Capsoni, Simona; Di Luzio, Anna; Vignone, Domenico; Malerba, Francesca; Paoletti, Francesca; Brandi, Rossella; Arisi, Ivan; Cattaneo, Antonino; Levi-Montalcini, Rita

    2012-02-07

    Nerve growth factor (NGF) was discovered because of its neurotrophic actions on sympathetic and sensory neurons in the developing chicken embryo. NGF was subsequently found to influence and regulate the function of many neuronal and non neuronal cells in adult organisms. Little is known, however, about the possible actions of NGF during early embryonic stages. However, mRNAs encoding for NGF and its receptors TrkA and p75(NTR) are expressed at very early stages of avian embryo development, before the nervous system is formed. The question, therefore, arises as to what might be the functions of NGF in early chicken embryo development, before its well-established actions on the developing sympathetic and sensory neurons. To investigate possible roles of NGF in the earliest stages of development, stage HH 11-12 chicken embryos were injected with an anti-NGF antibody (mAb αD11) that binds mature NGF with high affinity. Treatment with anti-NGF, but not with a control antibody, led to a dose-dependent inversion of the direction of axial rotation. This effect of altered rotation after anti NGF injection was associated with an increased cell death in somites. Concurrently, a microarray mRNA expression analysis revealed that NGF neutralization affects the expression of genes linked to the regulation of development or cell proliferation. These results reveal a role for NGF in early chicken embryo development and, in particular, in the regulation of somite survival and axial rotation, a crucial developmental process linked to left-right asymmetry specification.

  10. Comparison of Favorable Early-Stage Hodgkin's Lymphoma Treatments: A Single-Institution Review

    SciTech Connect

    Samant, Rajiv; Alomary, Ibraheem; Alsaeed, Eyad; Al-jasir, Badr; Bence-Bruckler, Isabelle; Cross, Peter; Genest, Paul; Huebsch, Lothar

    2010-03-15

    Purpose: To compare outcomes of patients receiving combined-modality chemotherapy and radiation (CMT) vs. other approaches for early-stage Hodgkin's lymphoma (HL). Methods and Materials: A review of patients with nonbulky, early-stage (IA/IIA) HL treated between 1984 and 2002 was performed to determine the treatment approaches used and the outcomes obtained. Results: There were 173 adult patients with newly diagnosed early-stage HL (49% men, 51% women, median age 33 [range 17-82] years). Treatment was as follows: extended-field radiotherapy alone (EFRT) 49%; chemotherapy alone (CTA) 13%; and CMT 38%. Among CMT patients, 36% received abbreviated doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy (three to four cycles) followed by involved-field radiotherapy. With a median follow-up of 8.3 years, the estimated 10-year relapse-free survival (RFS) and overall survival (OS) rates for the entire cohort were 78% and 85%, respectively. The 10-year RFS and OS rates for the various groups were as follows: 69% and 81% for EFRT; 78% and 84% for CTA; and 87% and 89% for CMT. The 10-year RFS rate was significantly higher (p < 0.01) among CMT patients. The use of EFRT has diminished from approximately 90% in the 1980s to virtually no use at present, whereas the use of CTA and CMT has increased significantly (p < 0.01). Conclusion: Early-stage HL treatment has changed dramatically over the past 2 decades, and our results support the superiority and continued use of CMT, specifically abbreviated-course chemotherapy and involved-field radiotherapy, as an appropriate treatment approach.

  11. Varying postresection lactate dehydrogenase with overall survival of early stage pancreatic cancer patients

    PubMed Central

    Xiao, Yuanyuan; Xie, Zhihui; Shao, Zhenyi; Chen, Wen; Xie, Hua; Qin, Guoyou; Zhao, Naiqing

    2017-01-01

    Abstract Several previously published studies revealed a hazardous role of pretreatment lactate dehydrogenase (LDH) in survival of advanced or metastatic pancreatic cancer (PC) patients. Nevertheless, in early stage PC patients who are eligible for curative resection, the prognostic role of postresection LDH has never been discussed. In this study, we aimed to explore the prognostic significance of varying postresection LDH among early stage PC patients. In total, 80 PC patients who received curative resection were retrospectively selected from a population-based electronic inpatients database which originated from Shanghai, China. A dynamic survival analysis method, counting process approach in combination with the multiple failure-time Cox model, was applied to evaluate the association between postresection LDH and OS. The multiple failure-time Cox model found that age, resection modality, and postresection LDH were significantly associated with OS: an elevated LDH (defined as > 250 U/L) was related to 2.93 (95% CI: 1.26–6.79) folds of death hazard. Further analysis disclosed an identifiable dose–response association between LDH and OS: compared with LDH≤155 U/L, the HRs for 155 U/L < LDH < 196 U/L, and LDH≥196 U/L were 2.07 (95% CI: 0.88–4.88) and 3.15 (95% CI: 1.30–7.59), respectively. Our study results suggest that postresection LDH is a prominent prognostic factor in this group of early stage PC patients. Maintaining normally ranged LDH after resection might bring about survival benefit in early stage PC patients. PMID:28328834

  12. Varying postresection lactate dehydrogenase with overall survival of early stage pancreatic cancer patients: A retrospective study.

    PubMed

    Xiao, Yuanyuan; Xie, Zhihui; Shao, Zhenyi; Chen, Wen; Xie, Hua; Qin, Guoyou; Zhao, Naiqing

    2017-03-01

    Several previously published studies revealed a hazardous role of pretreatment lactate dehydrogenase (LDH) in survival of advanced or metastatic pancreatic cancer (PC) patients. Nevertheless, in early stage PC patients who are eligible for curative resection, the prognostic role of postresection LDH has never been discussed. In this study, we aimed to explore the prognostic significance of varying postresection LDH among early stage PC patients. In total, 80 PC patients who received curative resection were retrospectively selected from a population-based electronic inpatients database which originated from Shanghai, China. A dynamic survival analysis method, counting process approach in combination with the multiple failure-time Cox model, was applied to evaluate the association between postresection LDH and OS. The multiple failure-time Cox model found that age, resection modality, and postresection LDH were significantly associated with OS: an elevated LDH (defined as > 250 U/L) was related to 2.93 (95% CI: 1.26-6.79) folds of death hazard. Further analysis disclosed an identifiable dose-response association between LDH and OS: compared with LDH≤155 U/L, the HRs for 155 U/L < LDH < 196 U/L, and LDH≥196 U/L were 2.07 (95% CI: 0.88-4.88) and 3.15 (95% CI: 1.30-7.59), respectively. Our study results suggest that postresection LDH is a prominent prognostic factor in this group of early stage PC patients. Maintaining normally ranged LDH after resection might bring about survival benefit in early stage PC patients.

  13. Gadolinium metallo nanocongregates as potential magnetosensors for detecting early stage cancers

    SciTech Connect

    Dutta, Ranu; Pandey, Avinash C.

    2015-04-27

    Gadolinium chelates and gadolinium based inorganic nanoparticles have been extensively studied, because of the high magnetic moment of gadolinium. Here, metallic gadolinium nanocongregates have been developed. Upon injecting these nanoparticles in the mice, they initially circulate in the blood stream and are localized at the cancer site, which could be visualized upon application of magnetic field hence acting as small magnetic nanosensors searching for even small cancers, detecting cancers at a very early stage.

  14. Early Stages of Figure–Ground Segregation during Perception of the Face–Vase

    PubMed Central

    Pitts, Michael A.; Martínez, Antígona; Brewer, James B.; Hillyard, Steven A.

    2011-01-01

    The temporal sequence of neural processes supporting figure–ground perception was investigated by recording ERPs associated with subjects’ perceptions of the face–vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects’ figure–ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ~150–200 msec) when that region was perceived as figure versus background. These components likely reflect an early “border ownership” stage, and a subsequent “figure–ground segregation” stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure–ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure–ground perception, each which are subject to modifications by selective attention. PMID:20146604

  15. DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer

    DTIC Science & Technology

    2015-08-01

    and select 330 samples for CNV analysis. Months :1 - 2 • Subtask 2 Prepare sections (10 μm) for microdissection to ensure>80% tumor. Months 3 - 8...Subtask 3 DNA preparation from microdissected specimens. Months 3 - 8 Major Task 2: To determine the copy number gain and loss for early stage high...to prepare chip compatible samples. Months : 9 - 18 • Subtask 2 Genomic abnormality analysis by IlluminaHumanOmniExpress-FFPE BeadChip system. Months

  16. Development of a Smart Diagnostics Platform for Early-Stage Screening of Breast Cancer

    DTIC Science & Technology

    2007-04-01

    thereby establishing non-invasive avenues for screening. The bioindicators that we are targeting are apolar metabolites indicative of early-stage...also yields the potential for part-per-million sensitivity. The current methods used to analyze bioindicators in urine and breath include high...Simulations Chemical Characterization NMR, FTIR, MS II. Preparation of Switchable Surfaces III. Testing Binding of Model Bioindicators 1. Self-Assembly

  17. [Signal exchange between plants and Arbuscular Mycorrhizae fungi during the early stage of symbiosis - A review].

    PubMed

    Duan, Qianqian; Yang, Xiaohong; Huang, Xianzhi

    2015-07-04

    Much is known about Arbuscular Mycorrhizae (AM), an important component of the ecosystem, whereas little is known about the signal exchange that allows mutual recognition and reprograming for the anticipated physical interaction. This review addresses the latest advances of signal exchange between plants and AM, including signal substances and their function, related genes and regulation function in the early stage of plant-fungal symbiosis.

  18. Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography

    PubMed Central

    Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

    2017-01-01

    Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. PMID:28107385

  19. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    PubMed

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D

    2015-11-01

    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.

  20. Proteomic Analysis of Phosphoproteins in the Rice Nucleus During the Early Stage of Seed Germination.

    PubMed

    Li, Ming; Yin, Xiaojian; Sakata, Katsumi; Yang, Pingfang; Komatsu, Setsuko

    2015-07-02

    The early stage of seed germination is the first step in the plant life cycle without visible morphological change. To investigate the mechanism controlling the early stage of rice seed germination, we performed gel-and label-free nuclear phosphoproteomics. A total of 3467 phosphopeptides belonging to 102 nuclear phosphoproteins from rice embryos were identified. Protein-synthesis-related proteins were mainly phosphorylated. During the first 24 h following imbibition, 115 nuclear phosphoproteins were identified, and significant changes in the phosphorylation level over time were observed in 29 phosphoproteins. Cluster analysis indicated that nucleotide-binding proteins and zinc finger CCCH- and BED-type proteins increased in abundance during the first 12 h of imbibition and then decreased. The in silico protein-protein interactions for 29 nuclear phosphoproteins indicated that the Sas10/Utp3 protein, which functions in snoRNA binding and gene silencing, was the center of the phosphoprotein network in nuclei. The germination rate of seeds was significantly slowed with phosphatase inhibitor treatment. The mRNA expression of the zinc finger CCCH-type protein did not change, and the zinc finger BED-type protein was upregulated in rice embryos during the early stage of germination with phosphatase inhibitor treatment. These results suggest that the phosphorylation and dephosphorylation of nuclear proteins are involved in rice seed germination. Furthermore, transcription factors such as zinc finger CCCH- and BED-type proteins might play a key role through nuclear phosphoproteins, and Sas10/Utp3 protein might interact with nuclear phosphoproteins in rice embryos to mediate the early stage of seed germination.

  1. Early stages of figure-ground segregation during perception of the face-vase.

    PubMed

    Pitts, Michael A; Martínez, Antígona; Brewer, James B; Hillyard, Steven A

    2011-04-01

    The temporal sequence of neural processes supporting figure-ground perception was investigated by recording ERPs associated with subjects' perceptions of the face-vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects' figure-ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ∼ 150-200 msec) when that region was perceived as figure versus background. These components likely reflect an early "border ownership" stage, and a subsequent "figure-ground segregation" stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure-ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure-ground perception, each which are subject to modifications by selective attention.

  2. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    SciTech Connect

    Ward, Matthew Christopher Pham, Yvonne D.; Kotecha, Rupesh; Zakem, Sara J.; Murray, Eric; Greskovich, John F.

    2016-04-01

    Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literature are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.

  3. Promoting Quality and Evidence-Based Care in Early-Stage Breast Cancer Follow-up

    PubMed Central

    Hayes, Daniel F.; Ramsey, Scott D.; Hortobagyi, Gabriel N.; Barlow, William E.; Gralow, Julie R.

    2014-01-01

    Evidence-based guidelines for long-term follow-up of early-stage breast cancer patients developed by oncology societies in the United States and Europe recommend that breast cancer survivors undergo regular evaluation with history and physical examination, as well as annual mammography. Routine blood tests, circulating tumor markers, and/or surveillance imaging studies beyond mammography are not recommended in the absence of concerning symptoms or physical examination findings because of lack of supportive clinical evidence. Despite these guidelines, studies have shown that 20% to 40% of oncologists assess serum tumor markers as part of routine monitoring of early-stage breast cancer patients. As part of efforts to both address the financial challenges confronting the health-care system and optimize patient outcomes, the American Society of Clinical Oncology’s Cost of Care Task Force identified adherence to breast cancer surveillance guidelines as an opportunity to improve care and reduce cost. However, these recommendations are based on trials done in an era of outdated technology and limited therapeutic options. It is possible that recent improvements in diagnostics and treatments could make earlier detection of recurrent disease important for improving both survival and quality of life outcomes. Research is necessary to further inform optimal breast cancer follow-up strategies, which could impact these recommendations. At this time, outside of well-conducted clinical trials, there is no role for ordering routine serial blood or imaging tests in monitoring for recurrence in early-stage breast cancer patients. PMID:24627271

  4. Two-stage biomarker panel study and estimation allowing early termination for futility.

    PubMed

    Zhao, Shanshan; Zheng, Yingye; Prentice, Ross L; Feng, Ziding

    2015-10-01

    Technological advances have yielded a wealth of biomarkers that have the potential to detect chronic diseases such as cancer. However, most biomarkers considered for further validation turn out not to have strong enough performance to be used in clinical practice. Group sequential designs that allow early termination for futility may be cost-effective for biomarker studies based on biobanks of stored specimens. Previous studies proposed a group sequential design for the validation of a single biomarker. In this article, we adapt a 2-stage design to the setting where a panel of candidate biomarkers are under investigation. Conditional estimators of the clinical performance are proposed under an updated risk model that uses all accrued data, and can be computed through resampling procedures. Under a special case where a multivariate binormal distribution applies for biomarkers following a suitable transformation, these estimators have analytical forms, alleviating the computational burden while retaining statistical efficiency. Performance of the proposed 2-stage design and estimators are compared with a traditional fixed-sample design and an existing 2-stage design that allows early termination but does not update the risk model with accrued information. Our proposed design and estimators show an ability to reduce sample size when the biomarker panel is not promising, while controlling rejection rate and gaining efficiency when the panel is promising. We apply the proposed methods to a biomarker panel development for the detection of high-grade prostate cancer in a study conducted within the National Cancer Institute's Early Detection Research Network.

  5. Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women

    PubMed Central

    Obeidat, Rana F.

    2015-01-01

    To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers’ support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system. PMID:27981122

  6. The use of adjuvant bisphophonates in the treatment of early-stage breast cancer.

    PubMed

    Mathew, Aju; Brufsky, Adam M

    2014-11-01

    Adjuvant treatment of breast cancer has resulted in significant improvement in breast cancer-related outcomes. In addition to chemotherapy and endocrine therapy, the bone-protective agents known as bisphosphonates have been extensively investigated for their putative antitumor effect. Backed by strong preclinical data from in vitro and in vivo models, several randomized clinical trials have evaluated the role of bisphosphonates in an adjuvant setting. The recent NSABP B-34 (National Surgical Adjuvant Breast and Bowel Project protocol B-34) and AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) studies found no disease-free survival benefit with clodronate and zoledronate, respectively, whereas the ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12) study found improvement in disease-free survival with zoledronate. Data from these trials suggested a beneficial effect of bisphosphonates in older, postmenopausal women and in premenopausal women treated with ovarian suppression. Given the acceptable toxicity profile of bisphosphonates, these agents could be a useful adjunct to adjuvant chemotherapy or endocrine treatment for early-stage breast cancer in a carefully selected subset of patients. This review aims to critically synthesize the results of clinical trials of adjuvant bisphosphonates in early-stage breast cancer, and to provide guidelines for the use of these agents in early-stage breast cancer.

  7. Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women.

    PubMed

    Obeidat, Rana F

    2015-01-01

    To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers' support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system.

  8. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

    PubMed Central

    López-Góngora, Mariana; Escartín, Antonio; Martínez-Horta, Saul; Fernández-Bobadilla, Ramón; Querol, Luis; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes. PMID:26322632

  9. Effects of Columbia River water on early life-stages of white sturgeon (Acipenser transmontanus).

    PubMed

    Tompsett, Amber R; Vardy, David W; Higley, Eric; Doering, Jon A; Allan, Marcie; Liber, Karsten; Giesy, John P; Hecker, Markus

    2014-03-01

    The white sturgeon (Acipenser transmontanus) population that resides in the Columbia River in British Columbia (BC), Canada, has suffered recruitment failures for more than three decades. During the summers of 2008 and 2009, studies were performed to determine whether exposure to water downstream of a metal smelter in Trail, BC affected survival or growth of early life-stages of white sturgeon through 60+ days post-fertilization (dpf). In both years, there were no significant differences in survival of fish that were exposed to water from downstream compared to water from upstream of the smelter. At 20-21dpf, average mortality was 2.4 percent and 12 percent in upstream water for 2008 and 2009, respectively, which was similar to the average mortality of 3.8 percent and 7.2 percent in downstream water for 2008 and 2009, respectively. Relatively great mortality after 20-21dpf complicated analysis of the subchronic exposure, but use of a survival analysis indicated that the average fish died at 25-29dpf, regardless of whether the water to which they were exposed came from upstream or downstream of the smelter. In addition, measured concentrations of metals in river water were less than the threshold for adverse effects on early life stages of white sturgeon. Based upon these analyses, it is not likely that current concentrations of metals in the Columbia River in southern BC are adversely affecting survival of early life stages of white sturgeon larvae.

  10. On the role of extracellular polymeric substances during early stages of Xylella fastidiosa biofilm formation.

    PubMed

    Lorite, Gabriela S; de Souza, Alessandra A; Neubauer, Daniel; Mizaikoff, Boris; Kranz, Christine; Cotta, Mônica A

    2013-02-01

    The structural integrity and protection of bacterial biofilms are intrinsically associated with a matrix of extracellular polymeric substances (EPS) produced by the bacteria cells. However, the role of these substances during biofilm adhesion to a surface remains largely unclear. In this study, the influence of EPS on Xylella fastidiosa biofilm formation was investigated. This bacterium is associated with economically important plant diseases; it presents a slow growth rate and thus allows us to pinpoint more precisely the early stages of cell-surface adhesion. Scanning electron microscopy and atomic force microscopy show evidence of EPS production in such early stages and around individual bacteria cells attached to the substrate surface even a few hours after inoculation. In addition, EPS formation was investigated via attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FTIR). To this end, X. fastidiosa cells were inoculated within an ATR liquid cell assembly. IR-ATR spectra clearly reveal EPS formation already during the early stages of X. fastidiosa biofilm formation, thereby providing supporting evidence for the hypothesis of the relevance of the EPS contribution to the adhesion process.

  11. Systemic Therapy for Early-Stage Breast Cancer: What the Plastic Surgeon Should Know.

    PubMed

    Teven, Chad M; Schmid, Daniel B; Sisco, Mark; Ward, James; Howard, Michael A

    2017-01-01

    Objective: We review the types, indications, and common regimens of systemic forms of therapy offered in early-stage breast cancer. We further detail the mechanism of action, approved uses, major toxicities, and relevance to breast reconstruction of specific agents. Methods: A review of the literature on PubMed and Cochrane databases was undertaken to define the indications and common regimens of systemic therapy in early-stage breast cancer. In addition, literature describing relevant information regarding specific systemic agents was reviewed. Results: The main objectives of systemic therapy, when provided in the perioperative setting, are to reduce the risk for future recurrence and prolong overall survival. Systemic forms of therapy consist of chemotherapy, hormonal therapy, and targeted therapy and are increasingly being offered to women with early-stage breast cancer. Similarly, as more women are diagnosed with disease that is amenable to surgical extirpation, rates of breast reconstruction are on the rise. Many agents have effects that may impact patient safety with respect to breast reconstruction. Conclusions: Increasingly, women with breast cancer receive 1 or more forms of systemic therapy during the course of their treatment. It is therefore of significant importance that plastic surgeons have a clear understanding of the issues surrounding the use of systemic agents.

  12. Systemic Therapy for Early-Stage Breast Cancer: What the Plastic Surgeon Should Know

    PubMed Central

    Teven, Chad M.; Schmid, Daniel B.; Sisco, Mark; Ward, James

    2017-01-01

    Objective: We review the types, indications, and common regimens of systemic forms of therapy offered in early-stage breast cancer. We further detail the mechanism of action, approved uses, major toxicities, and relevance to breast reconstruction of specific agents. Methods: A review of the literature on PubMed and Cochrane databases was undertaken to define the indications and common regimens of systemic therapy in early-stage breast cancer. In addition, literature describing relevant information regarding specific systemic agents was reviewed. Results: The main objectives of systemic therapy, when provided in the perioperative setting, are to reduce the risk for future recurrence and prolong overall survival. Systemic forms of therapy consist of chemotherapy, hormonal therapy, and targeted therapy and are increasingly being offered to women with early-stage breast cancer. Similarly, as more women are diagnosed with disease that is amenable to surgical extirpation, rates of breast reconstruction are on the rise. Many agents have effects that may impact patient safety with respect to breast reconstruction. Conclusions: Increasingly, women with breast cancer receive 1 or more forms of systemic therapy during the course of their treatment. It is therefore of significant importance that plastic surgeons have a clear understanding of the issues surrounding the use of systemic agents. PMID:28293332

  13. Hypokinesia of associated movement in Parkinson's disease: a symptom in early stages of the disease.

    PubMed

    Hoshiyama, M; Kaneoke, Y; Koike, Y; Takahashi, A; Watanabe, S

    1994-08-01

    We compared the degrees of impairment between intended voluntary movement and its simultaneous automatic associated movement in Parkinson's disease (PD). We studied wrist dorsiflexion as a movement associated with grip in 20 patients with PD and in 20 normal controls. The patients showed a significantly smaller dorsiflexion as compared with the controls. The decrease in associated movement was related to the severity of clinical stage of the disease, while gripping was performed well in each stage. The temporal relationship between grip and associated movement was the same for both groups of subjects. The patients showed no disturbance of amplitude or velocity for a single motor act of wrist dorsiflexion. Persons with PD have a greater reduction of automatic associated movement than intended voluntary movement. This may be one of the bases of clinical symptoms of PD patients in early stages of the disease.

  14. Treatment of early stage breast cancer by limited surgery and radical irradiation

    SciTech Connect

    Chu, A.M.; Cope, O.; Russo, R.; Wang, C.C.; Schulz, M.D.; Wang, C.; Rodkey, G.

    1980-01-01

    Eighty-five female patients with early stage breast cancer, i.e., Stage I and II were treated by limited surgery followed by radical radiation therapy at Massachusetts General Hospital between January, 1956 and December, 1974. Patients included those who were medically inoperable or who refused mastectomy. The 5-year survival rate was 83% and 76% for Stage I and II, respectively. The corresponding disease free survival (absolute) was 67% and 42%. Although the number of patients so treated is small, there was no significant difference in survival from the results of the radical mastectomy series at the same institution. No major complications were encountered. Seventeen of eighty-five patients developed minor problems; mostly fibrosis and minimal arm lymphedema stemmming from older orthovoltage equipment and treatment techniques. With the current availability of megavoltage equipment, improvements in techniques and dosimetry, complications should decrease. Combined limited surgery and radical radiation therapy should be considered in those patients where a radical mastectomy is not feasible because of psychological or medical problems. Since this procedure results in a cosmetically acceptable breast, radical radiation in early stage breast cancer seems a reasonable alternative to radical mastectomy.

  15. Quantitative study on guinea pig spermatogenesis shows a relative high percentage of early meiotic prophase stages.

    PubMed

    Rodríguez, Rosana E; Wettstein, Rodolfo M

    2004-05-01

    Meiosis is the special double cellular division characterized by the reduction of chromosome number of the final products and recombination of genetic information present in maternal and paternal homologous chromosomes. Early stages of meiotic prophase, leptotene and zygotene (L/Z), are functionally important since homologous chromosomes recognize, align, and pair during them. They are poorly represented in the seminiferous tubules of mammalian species, and this fact turns studies focused on these stages difficult to perform. As a consequence, the molecular bases of these important events are so far poorly known and understood in higher eukaryotes. The purpose of this work was to provide an advantageous experimental mammalian model (with a reasonable number of cells) for biochemical and molecular analysis of early meiotic prophase stages. Here, we present the results of our quantitative study on testes material of both immature and adult guinea pig specimens (Cavia porcellus). We show that their seminiferous tubules contain a comparatively high percentage of L/Z spermatocytes, as well as a very conspicuous chromosome bouquet at the L/Z transition, which points out this species as a well-suited one to address studies on such stages in mammals.

  16. Development sites, feeding modes and early stages of seven European Palloptera species (Diptera, Pallopteridae).

    PubMed

    Rotheray, Graham E

    2014-12-19

    Two hundred and ninety-eight rearing records and 87 larvae and puparia were obtained of seven species of Palloptera Fallén (Diptera, Pallopteridae), mainly in Scotland during 2012-2013. The third stage larva and puparium of each species were assessed morphologically and development sites and feeding modes investigated by rearing, observation and feeding tests. Early stages appear to be distinguished by the swollen, apico-lateral margins of the prothorax which are coated in vestiture and a poorly developed anal lobe with few spicules. Individual pallopteran species are separated by features of the head skeleton, locomotory spicules and the posterior respiratory organs. Five species can be distinguished by unique character states. Observations and feeding tests suggest that the frequently cited attribute of zoophagy is accidental and that saprophagy is the primary larval feeding mode with autumn/winter as the main period of development. Food plants were confirmed for flowerhead and stem developing species and rain is important for maintaining biofilms on which larvae feed. Due to difficulties in capturing adults, especially males, the distribution and abundance of many pallopteran species is probably underestimated. Better informed estimates are possible if early stages are included in biodiversity assessments. To facilitate this for the species investigated, a key to the third stage larva and puparium along with details on finding them, is provided. 

  17. Elevated risk of early reoperation in total hip replacement during the stage of unit closure

    PubMed Central

    Peltola, Mikko; Malmivaara, Antti; Paavola, Mika; Seitsalo, Seppo

    2016-01-01

    Background and purpose — The effects of launch or closure of an entire arthroplasty unit on the first or last patients treated in these units have not been studied. Using a 3-year follow-up, we investigated whether patients who were treated at the launch or closure stage of an arthroplasty unit of a hospital would have a higher risk of reoperation than patients treated in-between at the same units. Patients and methods — From the Finnish Arthroplasty Register, we identified all the units that had performed total joint arthroplasty and the units that were launched or closed in Finland between 1998 and 2011. The risks of reoperation within 3 years for the 41,748 total hip and knee replacements performed due to osteoarthritis in these units were modeled with Cox proportional-hazards regression, separately for hip and knee and for the launch and the closure stage. Results — The unadjusted and adjusted hazard ratios (HRs) for total hip and knee replacements performed in the initial stage of activity of the units that were launched were similar to the reoperation risks in patients who were operated in these units after the early stage of activity. The unadjusted and risk-adjusted HRs for early reoperation after total hip replacement (THR) were increased at the closure stage (adjusted HR = 1.8, 95% CI: 1.2–2.8). The reoperation risk at the closure stage after total knee replacement (TKR) was not increased. Interpretation — The results indicate that closure of units performing total hip replacements poses an increased risk of reoperation. Closures need to be managed carefully to prevent the quality from deteriorating when performing the final arthroplasties. PMID:26541178

  18. Abnormalities of plantar pressure distribution in early, intermediate, and late stages of diabetic neuropathy.

    PubMed

    Sacco, Isabel C N; Hamamoto, Adriana N; Tonicelli, Lucas M G; Watari, Ricky; Ortega, Neli R S; Sartor, Cristina D

    2014-09-01

    Inconsistent findings with regard to plantar pressure while walking in the diabetic population may be due to the heterogeneity of the studied groups resulting from the classification/grouping criteria adopted. The clinical diagnosis and classification of diabetes have inherent uncertainties that compromise the definition of its onset and the differentiation of its severity stages. A fuzzy system could improve the precision of the diagnosis and classification of diabetic neuropathy because it takes those uncertainties into account and combines different assessment methods. Here, we investigated how plantar pressure abnormalities evolve throughout different severity stages of diabetic polyneuropathy (absent, n=38; mild, n=20; moderate, n=47; severe, n=24). Pressure distribution was analysed over five areas while patients walked barefoot. Patients with mild neuropathy displayed an increase in pressure-time integral at the forefoot and a lower peak pressure at the heel. The peak and pressure-time integral under the forefoot and heel were aggravated in later stages of the disease (moderate and severe) compared with early stages of the disease (absent and mild). In the severe group, lower pressures at the lateral forefoot and hallux were observed, which could be related to symptoms that develop with the aggravation of neuropathy: atrophy of the intrinsic foot muscles, reduction of distal muscle activity, and joint stiffness. Although there were clear alterations over the forefoot and in a number of plantar areas with higher pressures within each severity stage, they did not follow the aggravation evolution of neuropathy classified by the fuzzy model. Based on these results, therapeutic interventions should begin in the early stages of this disease to prevent further consequences of the disease.

  19. Temperature Influences Selective Mortality during the Early Life Stages of a Coral Reef Fish

    PubMed Central

    Rankin, Tauna L.; Sponaugle, Su

    2011-01-01

    For organisms with complex life cycles, processes occurring at the interface between life stages can disproportionately impact survival and population dynamics. Temperature is an important factor influencing growth in poikilotherms, and growth-related processes are frequently correlated with survival. We examined the influence of water temperature on growth-related early life history traits (ELHTs) and differential mortality during the transition from larval to early juvenile stage in sixteen monthly cohorts of bicolor damselfish Stegastes partitus, sampled on reefs of the upper Florida Keys, USA over 6 years. Otolith analysis of settlers and juveniles coupled with environmental data revealed that mean near-reef water temperature explained a significant proportion of variation in pelagic larval duration (PLD), early larval growth, size-at-settlement, and growth during early juvenile life. Among all cohorts, surviving juveniles were consistently larger at settlement, but grew more slowly during the first 6 d post-settlement. For the other ELHTs, selective mortality varied seasonally: during winter and spring months, survivors exhibited faster larval growth and shorter PLDs, whereas during warmer summer months, selection on PLD reversed and selection on larval growth became non-linear. Our results demonstrate that temperature not only shapes growth-related traits, but can also influence the direction and intensity of selective mortality. PMID:21559305

  20. Cognitive deterioration in Alzheimer's disease: is the early course predictive of the later stages?

    PubMed

    Capitani, E; Cazzaniga, R; Francescani, A; Spinnler, H

    2004-10-01

    This study investigated the predictive value of the early progression rate of Alzheimer's disease on that of the later stages. We retrospectively evaluated 91 patients affected by possible Alzheimer's disease; the patients had been examined twice with the Milan overall dementia assessment (MODA) scale at an interval of 12 months (53 patients) or 24 months (38 patients). At the first assessment, speed of progression was calculated for each patient dividing the MODA difference from the normality threshold by the time elapsed from the cognitive decline onset. The second assessment of speed of progression was calculated dividing the difference between the two MODA scores by the time elapsed from the first examination. Patients with a slow progression rate in the early stage were unlikely to show a subsequent fast progression rate, and vice versa for patients with a fast early progression. A tool is provided for predicting the speed of cognitive decline of patients from a single MODA assessment. We suggest that, in future clinical trials on Alzheimer's disease, a stratification of participants based on the early rate of cognitive deterioration may be considered.

  1. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline

    PubMed Central

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a “pre-visible” stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65–84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  2. Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

    PubMed Central

    Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

    2016-01-01

    Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

  3. Open lung biopsy in early-stage acute respiratory distress syndrome

    PubMed Central

    Kao, Kuo-Chin; Tsai, Ying-Huang; Wu, Yao-Kuang; Chen, Ning-Hung; Hsieh, Meng-Jer; Huang, Shiu-Feng; Huang, Chung-Chi

    2006-01-01

    Introduction Acute respiratory distress syndrome (ARDS) has heterogeneous etiologies, rapid progressive change and a high mortality rate. To improve the outcome of ARDS, accurate diagnosis is essential to the application of effective early treatment. The present study investigated the clinical effects and safety of open lung biopsy (OLB) in patients with early-stage ARDS of suspected non-infectious origin. Methods We undertook a retrospective study of 41 patients with early-stage ARDS (defined as one week or less after intubation) who underwent OLB in two medical intensive care units of a tertiary care hospital from 1999 to 2005. Data analyzed included baseline characteristics, complication rate, pathological diagnoses, treatment alterations, and hospital survival. Results The age of patients was 55 ± 17 years (mean ± SD). The average ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) was 116 ± 43 mmHg (mean ± SD) at biopsy. Seventeen patients (41%) were immunocompromised. Postoperative complications occurred in 20% of patients (8/41). All biopsies provided a pathological diagnosis with a diagnostic yield of 100%. Specific pathological diagnoses were made for 44% of patients (18/41). Biopsy findings led to an alteration of treatment modality in 73% of patients (30/41). The treatment alteration rate was higher in patients with nonspecific diagnoses than in patients with specific diagnoses (p = 0.0024). Overall mortality was 50% (21/41) and was not influenced by age, gender, pre-OLB oxygenation, complication rate, pathological results, and alteration of treatment. There was no surgery-related mortality. The survival rate for immunocompromised patients was better than that for immunocompetent patients (71% versus 33%; p = 0.0187) in this study. Conclusion Our retrospective study suggests that OLB was a useful and acceptably safe diagnostic procedure in some selected patients with early-stage ARDS. PMID:16859510

  4. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

    PubMed Central

    Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

    2014-01-01

    Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

  5. Lexical Access in Early Stages of Visual Word Processing: A Single-Trial Correlational MEG Study of Heteronym Recognition

    ERIC Educational Resources Information Center

    Solomyak, Olla; Marantz, Alec

    2009-01-01

    We present an MEG study of heteronym recognition, aiming to distinguish between two theories of lexical access: the "early access" theory, which entails that lexical access occurs at early (pre 200 ms) stages of processing, and the "late access" theory, which interprets this early activity as orthographic word-form identification rather than…

  6. Spatial variations in mortality in pelagic early life stages of a marine fish (Gadus morhua)

    NASA Astrophysics Data System (ADS)

    Langangen, Øystein; Stige, Leif C.; Yaragina, Natalia A.; Ottersen, Geir; Vikebø, Frode B.; Stenseth, Nils Chr.

    2014-09-01

    Mortality of pelagic eggs and larvae of marine fish is often assumed to be constant both in space and time due to lacking information. This may, however, be a gross oversimplification, as early life stages are likely to experience large variations in mortality both in time and space. In this paper we develop a method for estimating the spatial variability in mortality of eggs and larvae. The method relies on survey data and physical-biological particle-drift models to predict the drift of ichthyoplankton. Furthermore, the method was used to estimate the spatially resolved mortality field in the egg and larval stages of Barents Sea cod (Gadus morhua). We analyzed data from the Barents Sea for the period between 1959 and 1993 when there are two surveys available: a spring and a summer survey. An individual-based physical-biological particle-drift model, tailored to the egg and larval stages of Barents Sea cod, was used to predict the drift trajectories from the observed stage-specific distributions in spring to the time of observation in the summer, a drift time of approximately 45 days. We interpreted the spatial patterns in the differences between the predicted and observed abundance distributions in summer as reflecting the spatial patterns in mortality over the drift period. Using the estimated mortality fields, we show that the spatial variations in mortality might have a significant impact on survival to later life stages and we suggest that there may be trade-offs between increased early survival in off shore regions and reduced probability of ending up in the favorable nursing grounds in the Barents Sea. In addition, we show that accounting for the estimated mortality field, improves the correlation between a simulated recruitment index and observation-based indices of juvenile abundance.

  7. Plasma Epidermal Growth Factor Decreased in the Early Stage of Parkinson’s Disease

    PubMed Central

    Jiang, Qian-Wen; Wang, Cheng; Zhou, Yi; Hou, Miao-Miao; Wang, Xi; Tang, Hui-Dong; Wu, Yi-Wen; Ma, Jian-Fang; Chen, Sheng-Di

    2015-01-01

    Epidermal growth factor (EGF) is a neurotrophic factor that plays an important role in Parkinson’s disease (PD). We measured plasma EGF level in PD, essential tremor (ET) and normal controls to investigate whether it changes in PD and whether it is associated with motor and non-motor symptoms of PD. 100 patients with PD, 40 patients with ET as disease control and 76 healthy persons were enrolled in the present study. Motor and non-motor symptoms were assessed by different scales. Plasma EGF levels of three groups were measured by enzyme-linked immunosorbent assay kit. Spearman test and linear logistics regression model were used to test the correlation of EGF with motor and non-motor symptoms of PD. Plasma EGF level was significantly decreased in early PD patients compared with normal control, but not in advanced PD patients. Interestingly, plasma EGF level was significantly increased in advanced PD and total PD patients compared with ET patients, but not in early PD patients. In addition, plasma EGF level was correlated with UPDRS-III scores in PD. Also plasma EGF level was correlated with UPDRS-III scores and NMS scores in early PD. Our results suggested that plasma EGF decreased in the early stage of PD and increased later on in the PD disease course. Also, plasma EGF level was increased significantly in PD compared with ET patients and correlated with motor and non-motor symptoms in early PD. PMID:26029474

  8. Subsets of a Large Cognitive Battery Better Power Clinical Trials on Early Stage Alzheimer Disease

    PubMed Central

    Xiong, Chengjie; Weng, Hua; Bennett, David A.; Boyle, Patricia A.; Shah, Raj C.; Fague, Scot; Hall, Charles B.; Lipton, Richard B.; Morris, John C.

    2014-01-01

    Background/Aims Cognitive batteries routinely used by the Alzheimer disease (AD) research community may contain items uninformative for tracking disease progression to power clinical trials on early stage AD. We aim to identify subsets of the most informative items from an existing cognitive battery for better powering clinical trials on early AD. Methods Longitudinal change in item scores from the battery was associated with the onset of Mild Cognitive Impairment (MCI) in 1513 elderly individuals. Items whose longitudinal changes were correlated with the onset of MCI were selected as informative for tracking the early cognitive progression. Results 226 items in the battery were annually assessed over a follow-up of up to 13 years. Changes of item scores over time from 187 items were significantly correlated with the onset of MCI. For clinical trials on preclinical AD and on MCI, informative items permit smaller or similar sample sizes as compared to the entire battery, whereas uninformative items require much larger sample sizes. Conclusions Longitudinal changes in item scores from about 17% of items in the cognitive battery are uninformative for tracking early disease progression. Clinical trials on early AD can be better powered using informative items rather than the entire battery. PMID:25376544

  9. HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

    PubMed Central

    Dirk, Brennan S.; Pawlak, Emily N.; Johnson, Aaron L.; Van Nynatten, Logan R.; Jacob, Rajesh A.; Heit, Bryan; Dikeakos, Jimmy D.

    2016-01-01

    A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the cell. Furthermore, super-resolution imaging identified that the Nef:MHC-I BiFC complex transits through both early and late endosomes before ultimately residing at the trans-Golgi network. Together we demonstrate the importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses. PMID:27841315

  10. Large spinose microfossils in Ediacaran rocks as resting stages of early animals.

    PubMed

    Cohen, Phoebe A; Knoll, Andrew H; Kodner, Robin B

    2009-04-21

    Large (>100 microm), profusely ornamented microfossils comprise a distinctive paleontological component of sedimentary rocks deposited during the Ediacaran Period (635-542 million years ago). Smaller spinose fossils in Paleozoic rocks have commonly been interpreted as algal cysts or phycomata, but the Ediacaran populations differ from modern algal analogs in size, shape, ultrastructure, and internal contents. In contrast, cysts formed during the diapause egg-resting stages of many metazoans share features of size, ornamentation, and internal contents with large ornamented Ediacaran microfossils (LOEMs). Moreover, transmission electron microscopic observations of animal-resting cysts reveal a 3-layer wall ultrastructure comparable to that of LOEM taxa. Interpretation of these distinctive Ediacaran microfossils as resting stages in early metazoan life cycles offers additional perspectives on their functional morphology and stratigraphic distribution. Based on comparisons with modern marine invertebrates, the recalcitrant life stage represented by LOEMs is interpreted as an evolutionary response to prolonged episodes of bottom water anoxia in Ediacaran shelf and platform environments. As predicted by this hypothesis, the later Ediacaran disappearance of LOEM taxa coincides with geochemical evidence for a marked decline in the extent of oxygen-depleted waters impinging on continental shelves and platforms. Thus, the form, diversity, and stratigraphic range of LOEMs illuminate life cycle evolution in early animals as influenced by the evolving redox state of the oceans.

  11. Involved Node Radiation Therapy: An Effective Alternative in Early-Stage Hodgkin Lymphoma

    SciTech Connect

    Maraldo, Maja V.; Aznar, Marianne C.; Vogelius, Ivan R.; Petersen, Peter M.; Specht, Lena

    2013-03-15

    Purpose: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. Methods and Materials: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. Results: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. Conclusions: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.

  12. Challenges and developments in research of the early stages of bipolar disorder.

    PubMed

    Brietzke, Elisa; Rosa, Adriane R; Pedrini, Mariana; Noto, Mariane N; Kapczinski, Flavio; Scott, Jan

    2016-01-01

    Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.

  13. Early-stage primary signet ring cell carcinoma of the colon

    PubMed Central

    Kim, Jae Hyun; Park, Seun Ja; Park, Moo In; Moon, Won; Kim, Sung Eun

    2013-01-01

    Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature. PMID:23840131

  14. Changes of statistical structural fluctuations unveils an early compacted degraded stage of PNS myelin

    NASA Astrophysics Data System (ADS)

    Poccia, Nicola; Campi, Gaetano; Ricci, Alessandro; Caporale, Alessandra S.; di Cola, Emanuela; Hawkins, Thomas A.; Bianconi, Antonio

    2014-06-01

    Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered.

  15. Pesticides in urban streams and early life stages of Pacific coho salmon.

    PubMed

    King, Kerensa A; Grue, Christian E; Grassley, James M; Fisk, Robert J

    2013-04-01

    Pesticides are frequently detected in urban streams and are believed to be primarily the result of homeowner use. Although concentrations in most cases are low (<1 µg/L), there is concern that pesticide inputs threaten efforts to restore and enhance salmon habitat. The authors exposed early life stages of coho salmon (Oncorhynchus kisutch) to a pesticide mixture ("cocktail") representative of those pesticides most frequently reported in urban streams in western Washington State, USA. Life stages were continuously exposed to pulses of the cocktail simulating those in urban streams in fall and winter when coho salmon eggs and sac fry are present. Nominal concentrations of eight herbicides, two insecticides, a fungicide, and a breakdown product were the maximum detected. Fertilization, hatching success, survival, deformities, and growth of fry were not significantly affected. A reduction in fertilization success (19-25%) was not reproducible even when gametes were exposed to 100 times the maximum concentrations detected. Based on the end points examined in the present study, the results suggest that direct exposure to the pesticides most frequently detected in urban streams in western Washington does not impair early life stages of coho salmon and is not a major factor governing the recovery of salmon populations. The extent to which pesticide exposure would affect smoltification, outmigration, and ocean survival needs to be determined.

  16. Genome-scale transcriptomic insights into early-stage fruit development in woodland strawberry Fragaria vesca.

    PubMed

    Kang, Chunying; Darwish, Omar; Geretz, Aviva; Shahan, Rachel; Alkharouf, Nadim; Liu, Zhongchi

    2013-06-01

    Fragaria vesca, a diploid woodland strawberry with a small and sequenced genome, is an excellent model for studying fruit development. The strawberry fruit is unique in that the edible flesh is actually enlarged receptacle tissue. The true fruit are the numerous dry achenes dotting the receptacle's surface. Auxin produced from the achene is essential for the receptacle fruit set, a paradigm for studying crosstalk between hormone signaling and development. To investigate the molecular mechanism underlying strawberry fruit set, next-generation sequencing was employed to profile early-stage fruit development with five fruit tissue types and five developmental stages from floral anthesis to enlarged fruits. This two-dimensional data set provides a systems-level view of molecular events with precise spatial and temporal resolution. The data suggest that the endosperm and seed coat may play a more prominent role than the embryo in auxin and gibberellin biosynthesis for fruit set. A model is proposed to illustrate how hormonal signals produced in the endosperm and seed coat coordinate seed, ovary wall, and receptacle fruit development. The comprehensive fruit transcriptome data set provides a wealth of genomic resources for the strawberry and Rosaceae communities as well as unprecedented molecular insight into fruit set and early stage fruit development.

  17. Relationship between early and late stages of information processing: an event-related potential study

    PubMed Central

    Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2012-01-01

    The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

  18. Large spinose microfossils in Ediacaran rocks as resting stages of early animals

    PubMed Central

    Cohen, Phoebe A.; Knoll, Andrew H.; Kodner, Robin B.

    2009-01-01

    Large (>100 μm), profusely ornamented microfossils comprise a distinctive paleontological component of sedimentary rocks deposited during the Ediacaran Period (635–542 million years ago). Smaller spinose fossils in Paleozoic rocks have commonly been interpreted as algal cysts or phycomata, but the Ediacaran populations differ from modern algal analogs in size, shape, ultrastructure, and internal contents. In contrast, cysts formed during the diapause egg-resting stages of many metazoans share features of size, ornamentation, and internal contents with large ornamented Ediacaran microfossils (LOEMs). Moreover, transmission electron microscopic observations of animal-resting cysts reveal a 3-layer wall ultrastructure comparable to that of LOEM taxa. Interpretation of these distinctive Ediacaran microfossils as resting stages in early metazoan life cycles offers additional perspectives on their functional morphology and stratigraphic distribution. Based on comparisons with modern marine invertebrates, the recalcitrant life stage represented by LOEMs is interpreted as an evolutionary response to prolonged episodes of bottom water anoxia in Ediacaran shelf and platform environments. As predicted by this hypothesis, the later Ediacaran disappearance of LOEM taxa coincides with geochemical evidence for a marked decline in the extent of oxygen-depleted waters impinging on continental shelves and platforms. Thus, the form, diversity, and stratigraphic range of LOEMs illuminate life cycle evolution in early animals as influenced by the evolving redox state of the oceans. PMID:19366668

  19. Diversity and dynamics of bacterial communities in early life stages of the Caribbean coral Porites astreoides

    PubMed Central

    Sharp, Koty H; Distel, Dan; Paul, Valerie J

    2012-01-01

    In this study, we examine microbial communities of early developmental stages of the coral Porites astreoides by sequence analysis of cloned 16S rRNA genes, terminal restriction fragment length polymorphism (TRFLP), and fluorescence in situ hybridization (FISH) imaging. Bacteria are associated with the ectoderm layer in newly released planula larvae, in 4-day-old planulae, and on the newly forming mesenteries surrounding developing septa in juvenile polyps after settlement. Roseobacter clade-associated (RCA) bacteria and Marinobacter sp. are consistently detected in specimens of P. astreoides spanning three early developmental stages, two locations in the Caribbean and 3 years of collection. Multi-response permutation procedures analysis on the TRFLP results do not support significant variation in the bacterial communities associated with P. astreoides larvae across collection location, collection year or developmental stage. The results are the first evidence of vertical transmission (from parent to offspring) of bacteria in corals. The results also show that at least two groups of bacterial taxa, the RCA bacteria and Marinobacter, are consistently associated with juvenile P. astreoides against a complex background of microbial associations, indicating that some components of the microbial community are long-term associates of the corals and may impact host health and survival. PMID:22113375

  20. Dynamics of laser ablation at the early stage during and after ultrashort pulse

    NASA Astrophysics Data System (ADS)

    Ilnitsky, D. K.; Khokhlov, V. A.; Zhakhovsky, V. V.; Petrov, Yu V.; Migdal, K. P.; Inogamov, N. A.

    2016-11-01

    Study of material flow in two-temperature states is needed for a fundamental understanding the physics of femtosecond laser ablation. To explore phenomena at a very early stage of laser action on a metallic target our in-house two-temperature hydrodynamics code is used here. The early stage covers duration of laser pulse with next first few picoseconds. We draw attention to the difference in behavior at this stage between the cases: (i) of an ultrathin film (thickness of order of skin depth d skin or less), (ii) thin films (thickness of a film is 4-7 of d skin for gold), and (iii) bulk targets (more than 10d skin for gold). We demonstrate that these differences follow from a competition among conductive cooling of laser excited electrons in a skin layer, electron-ion coupling, and hydrodynamics of unloading caused by excess of pressure of excited free electrons. Conductive cooling of the skin needs a heat sink, which is performed by the cold material outside the skin. Such sink is unavailable in the ultrathin films.

  1. Developing an inventor support service which performs early stage market and manufacturing evaluations. [Final Report

    SciTech Connect

    Not Available

    1991-10-01

    American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was to establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.

  2. Developing an inventor support service which performs early stage market and manufacturing evaluations. Final report

    SciTech Connect

    Not Available

    1991-10-01

    American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was to establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.

  3. Imaging and detection of early stage dental caries with an all-optical photoacoustic microscope

    NASA Astrophysics Data System (ADS)

    Hughes, D. A.; Sampathkumar, A.; Longbottom, C.; Kirk, K. J.

    2015-01-01

    Tooth decay, at its earliest stages, manifests itself as small, white, subsurface lesions in the enamel. Current methods for detection in the dental clinic are visual and tactile investigations, and bite-wing X-ray radiographs. These techniques suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease due to the small size (<100μm) of the lesion. A fine-resolution (600 nm) ultra-broadband (200 MHz) all-optical photoacoustic microscopy system was is used to image the early signs of tooth decay. Ex-vivo tooth samples exhibiting white spot lesions were scanned and were found to generate a larger (one order of magnitude) photoacoustic (PA) signal in the lesion regions compared to healthy enamel. The high contrast in the PA images potentially allows lesions to be imaged and measured at a much earlier stage than current clinical techniques allow. PA images were cross referenced with histology photographs to validate our experimental results. Our PA system provides a noncontact method for early detection of white-spot lesions with a high detection bandwidth that offers advantages over previously demonstrated ultrasound methods. The technique provides the sensing depth of an ultrasound system, but with the spatial resolution of an optical system.

  4. Diversity and dynamics of bacterial communities in early life stages of the Caribbean coral Porites astreoides.

    PubMed

    Sharp, Koty H; Distel, Dan; Paul, Valerie J

    2012-04-01

    In this study, we examine microbial communities of early developmental stages of the coral Porites astreoides by sequence analysis of cloned 16S rRNA genes, terminal restriction fragment length polymorphism (TRFLP), and fluorescence in situ hybridization (FISH) imaging. Bacteria are associated with the ectoderm layer in newly released planula larvae, in 4-day-old planulae, and on the newly forming mesenteries surrounding developing septa in juvenile polyps after settlement. Roseobacter clade-associated (RCA) bacteria and Marinobacter sp. are consistently detected in specimens of P. astreoides spanning three early developmental stages, two locations in the Caribbean and 3 years of collection. Multi-response permutation procedures analysis on the TRFLP results do not support significant variation in the bacterial communities associated with P. astreoides larvae across collection location, collection year or developmental stage. The results are the first evidence of vertical transmission (from parent to offspring) of bacteria in corals. The results also show that at least two groups of bacterial taxa, the RCA bacteria and Marinobacter, are consistently associated with juvenile P. astreoides against a complex background of microbial associations, indicating that some components of the microbial community are long-term associates of the corals and may impact host health and survival.

  5. Circulating microRNAs, possible indicators of progress of rat hepatocarcinogenesis from early stages.

    PubMed

    Sukata, Tokuo; Sumida, Kayo; Kushida, Masahiko; Ogata, Keiko; Miyata, Kaori; Yabushita, Setsuko; Uwagawa, Satoshi

    2011-01-15

    MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level, are believed promising biomarkers for several diseases as well as a novel target of drugs, including cancer. In particular, miRNAs might allow detection of early stages of carcinogenesis. The present study was conducted to provide concrete evidence using chemical-induced hepatocarcinogenesis in rat as a model. We thereby observed aberrant fluctuation of circulating miRNAs in the serum of rats not only with neoplastic lesions such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), but also with preneoplastic lesions, such as foci of hepatocellular alteration (FHA). Additional qRT-PCR analysis revealed gradual elevation of some circulating miRNAs (i.e., let-7a, let-7f, miR-34a, miR-98, miR-331, miR-338 and miR-652) with progress of hepatocarcinogenesis. Interestingly, increased levels of let-7a, let-7f and miR-98 were statistically significant even in the serum of rats at very early stages. These findings provide the first evidences that circulating miRNAs have the potential to predict carcinogenesis at earlier stages, preneoplastic lesions than with previous biomarkers and that they might be utilized to monitor the progress of tumor development.

  6. A mid-term follow-up of Koutsogiannis’ osteotomy in adult-acquired flatfoot stage II and “early stage III”

    PubMed Central

    Arvinius, Camilla; Manrique, Elena; Urda, Antonio; Cardoso, Zulema; Galeote, Jose Enrique; Marco, Fernando

    2017-01-01

    Introduction: Koutsogiannis’ osteotomy has been widely described to treat adult-acquired flatfoot. However, few articles describe its midterm follow-up. Our aim was to study clinical and radiological outcomes at least one year after surgery and to analyze whether a combined procedure on the medial soft tissue affected these outcomes. Methods: We performed a retrospective study of 30 feet of patients who underwent a Koutsogiannis’ osteotomy due to adult-acquired flatfoot stage II and “early stage III”: a stage III acquired flatfoot without any important structural deformities. The parameters studied were additional medial soft tissue procedures, clinical outcome through the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and midfoot score as well as complications and radiological measurements. Results: Sixteen cases were “early stage III” and 14 stage II. Thirteen patients underwent an associated posterior tibial tendon (PTT) revision: in three cases an end-to-end suture was possible, seven cases needed a FDL transposition, and three underwent synovectomy. Statistically significant improvement was found in the AOFAS score although no significant changes were seen radiologically. No additional benefit was found with the revision of the posterior tibial tendon. As to clinical and radiological results, no differences were found between stage II and “early stage III”. Five cases presented a mild dysesthesia but only one patient needed neurolysis. Conclusions: We consider the Koutsogiannis’ osteotomy to be a safe and effective procedure to reduce pain in patients with stage II and “early stage III” adult-acquired flatfoot. PMID:28304274

  7. [Stage 3 recommendations--the early recognition of breast cancer in Germany. Abridged version for medical practitioners].

    PubMed

    Schulz, K-D; Kreienberg, R; Fischer, R; Albert, U-S

    2003-06-01

    The Aim of this level 3 good clinical practice guideline is to help physicians, women and patients in decision making about the appropriate health care for early detection of breast cancer. The principle of early detection of breast cancer comprise the detection and diagnosis of premalignant breast tumors (stage 0, Carcinoma in situ), risk reduction of cancer development as well as the detection and diagnosis of breast cancer at an early stage (stage I), with a 90% chance of cure as shown by a large number of clinical trials. To establish a nation wide, comprehensive quality assuring program for the early detection of breast cancer the guideline summarized in the following paper offers the basis for a timely mortality reduction of breast cancer. The cure of early stage disease will be additionally possible by less invasive treatment allowing patients to maintain quality of life. The guideline leads to a major improvement of women's health care.

  8. Functional magnetic resonance imaging and cognition at the very early stage of MS.

    PubMed

    Audoin, Bertrand; Au Duong, My Van; Malikova, Irina; Confort-Gouny, Sylviane; Ibarrola, Danielle; Cozzone, Patrick J; Pelletier, Jean; Ranjeva, Jean-Philippe

    2006-06-15

    Dysfunction of high controlled information processing is present in patients with multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is that disruption of communication inside large-scale cortical networks, occurring as a consequence of white matter damage, may constitute the anatomical substrate of cognitive impairment at the very early stage of MS. Disturbance of interregional synchronization might be the main pathogenic factor in controlled information processing deficiency in early MS. Preliminary functional MRI studies (fMRI) have provided important clues to corroborate the connectivity hypotheses. First, brain connectivity assessed by fMRI has brought new data about the influence of diffuse white matter damage on connectivity efficiency inside large-scale networks. These studies have suggested that connectivity disturbances occur inside the working memory network in patients at the very early stage of MS and appear related to the extent of structural white matter damage. Also, fMRI studies have suggested that patients may partially compensate for connectivity impairment by a greater cognitive control. Such a compensatory mechanism could limit the determinant functional impact of diffuse white matter damage on high controlled information processing.

  9. Accelerated Partial Breast Irradiation Using Only Intraoperative Electron Radiation Therapy in Early Stage Breast Cancer

    SciTech Connect

    Maluta, Sergio; Dall'Oglio, Stefano; Marciai, Nadia; Gabbani, Milena; Franchini, Zeno; Pietrarota, Paolo; Meliado, Gabriele; Guariglia, Stefania; Cavedon, Carlo

    2012-10-01

    Background: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results: With a mean follow-up of 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.

  10. Effect of salicylic acid on early life stages of common carp (Cyprinus carpio).

    PubMed

    Zivna, Dana; Sehonova, Pavla; Plhalova, Lucie; Marsalek, Petr; Blahova, Jana; Prokes, Miroslav; Divisova, Lenka; Stancova, Vlasta; Dobsikova, Radka; Tichy, Frantisek; Siroka, Zuzana; Svobodova, Zdenka

    2015-07-01

    Environmental concentrations of pharmaceutical residues are often low; nevertheless, they are designed to have biological effects at low doses. The aim of this study was to assess the effects of salicylic acid on the growth and development of common carp (Cyprinus carpio) early life stages with respect to antioxidant defence enzymes. An embryo-larval toxicity test lasting 34 days was performed according to OECD guidelines 210 (Fish, Early-life Stage Toxicity Test). The tested concentrations were 0.004, 0.04, 0.4, 4 and 20mg/l of salicylic acid. Hatching, early ontogeny, and both morphometric and condition characteristics were significantly influenced by subchronic exposure to salicylic acid. Also, changes in antioxidant enzyme activity and an increase in lipid peroxidation were observed. The LOEC value was found to be 0.004 mg/l salicylic acid. The results of our study confirm the suggestion that subchronic exposure to salicylic acid at environmental concentrations can have significant effects on aquatic vertebrates.

  11. Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach

    PubMed Central

    Lewis, S; Foltynie, T; Blackwell, A; Robbins, T; Owen, A; Barker, R

    2005-01-01

    Objective: To investigate the heterogeneity of idiopathic Parkinson's disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson's disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment. PMID:15716523

  12. An informational diversity framework, illustrated with sexually deceptive orchids in early stages of speciation.

    PubMed

    Smouse, Peter E; Whitehead, Michael R; Peakall, Rod

    2015-11-01

    Reconstructing evolutionary history for emerging species complexes is notoriously difficult, with newly isolated taxa often morphologically cryptic and the signature of reproductive isolation often restricted to a few genes. Evidence from multiple loci and genomes is highly desirable, but multiple inputs require 'common currency' translation. Here we deploy a Shannon information framework, converting into diversity analogue, which provides a common currency analysis for maternally inherited haploid and bi-parentally inherited diploid nuclear markers, and then extend that analysis to construction of minimum-spanning networks for both genomes. The new approach is illustrated with a quartet of cryptic congeners from the sexually deceptive Australian orchid genus Chiloglottis, still in the early stages of speciation. Divergence is more rapid for haploid plastids than for nuclear markers, consistent with the effective population size differential (N(ep) < (N(en)), but divergence patterns are broadly correlated for the two genomes. There are nevertheless intriguing discrepancies between the emerging plastid and nuclear signals of early phylogenetic radiation of these taxa, and neither pattern is entirely consistent with the available information on the sexual cues used by the orchids to lure the pollinators enforcing reproductive isolation. We describe possible extensions of this methodology to multiple ploidy levels and other types of markers, which should increase the range of application to any taxonomic assemblage in the very early stages of reproductive isolation and speciation.

  13. Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS.

    PubMed

    Vaknin-Dembinsky, Adi; Brass, Steven D; Brass, Steven; Gandhi, Roopali; Weiner, Howard L

    2008-03-01

    IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, IL-15 may be an important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS.

  14. Discovery of piRNAs Pathway Associated with Early-Stage Spermatogenesis in Chicken.

    PubMed

    Xu, Lu; Qiu, Lingling; Chang, Guobin; Guo, Qixin; Liu, Xiangping; Bi, Yulin; Zhang, Yu; Wang, Hongzhi; Li, Zhiteng; Guo, Xiaoming; Wan, Fang; Zhang, Yang; Xu, Qi; Chen, Guohong

    2016-01-01

    Piwi-interacting RNAs (piRNAs) play a key role in spermatogenesis. Here, we describe the piRNAs profiling of primordial germ cells (PGCs), spermatogonial stem cells (SSCs), and the spermatogonium (Sp) during early-stage spermatogenesis in chicken. We obtained 31,361,989 reads from PGCs, 31,757,666 reads from SSCs, and 46,448,327 reads from Sp cells. The length distribution of piRNAs in the three samples showed peaks at 33 nt. The resulting genes were subsequently annotated against the Gene Ontology (GO) database. Five genes (RPL7A, HSPA8, Pum1, CPXM2, and PRKCA) were found to be involved in cellular processes. Interactive pathway analysis (IPA) further revealed three important pathways in early-stage spermatogenesis including the FGF, Wnt, and EGF receptor signaling pathways. The gene Pum1 was found to promote germline stem cell proliferation, but it also plays a role in spermatogenesis. In conclusion, we revealed characteristics of piRNAs during early spermatogonial development in chicken and provided the basis for future research.

  15. Astronomical constraints on the duration of the Early Jurassic Pliensbachian Stage and global climatic fluctuations

    NASA Astrophysics Data System (ADS)

    Ruhl, Micha; Hesselbo, Stephen P.; Hinnov, Linda; Jenkyns, Hugh C.; Xu, Weimu; Riding, James B.; Storm, Marisa; Minisini, Daniel; Ullmann, Clemens V.; Leng, Melanie J.

    2016-12-01

    The Early Jurassic was marked by multiple periods of major global climatic and palaeoceanographic change, biotic turnover and perturbed global geochemical cycles, commonly linked to large igneous province volcanism. This epoch was also characterised by the initial break-up of the super-continent Pangaea and the opening and formation of shallow-marine basins and ocean gateways, the timing of which are poorly constrained. Here, we show that the Pliensbachian Stage and the Sinemurian-Pliensbachian global carbon-cycle perturbation (marked by a negative shift in δ13 C of 2- 4 ‰), have respective durations of ∼8.7 and ∼2 Myr. We astronomically tune the floating Pliensbachian time scale to the 405 Kyr eccentricity solution (La2010d), and propose a revised Early Jurassic time scale with a significantly shortened Sinemurian Stage duration of 6.9 ± 0.4 Myr. When calibrated against the new time scale, the existing Pliensbachian seawater 87Sr/86Sr record shows relatively stable values during the first ∼2 Myr of the Pliensbachian, superimposed on the long-term Early Jurassic decline in 87Sr/86Sr. This plateau in 87Sr/86Sr values coincides with the Sinemurian-Pliensbachian boundary carbon-cycle perturbation. It is possibly linked to a late phase of Central Atlantic Magmatic Province (CAMP) volcanism that induced enhanced global weathering of continental crustal materials, leading to an elevated radiogenic strontium flux to the global ocean.

  16. Experimental early-stage coalification of a peat sample and a peatified wood sample from Indonesia

    USGS Publications Warehouse

    Orem, W.H.; Neuzil, S.G.; Lerch, H.E.; Cecil, C.B.

    1996-01-01

    Experimental coalification of a peat sample and a buried wood sample from domed peat deposits in Indonesia was carried out to examine chemical structural changes in organic matter during early-stage coalification. The experiment (125 C, 408 atm lithostatic pressure, and 177 atm fluid pressure for 75 days) was designed to maintain both lithostatic and fluid pressure on the sample, but allow by-products that may retard coalification to escape. We refer to this design as a geologically open system. Changes in the elemental composition, and 13C NMR and FTIR spectra of the peat and wood after experimental coalification suggest preferential thermal decomposition of O-containing aliphatic organic compounds (probably cellulose) during early-stage coalification. The elemental compositions and 13C NMR spectra of the experimentally coalified peat and wood were generally similar to those of Miocene coal and coalified wood samples from Indonesia. Yields of lignin phenols in the peat and wood samples decreased following experimental coalification; the wood sample exhibited a larger change. Lignin phenol yields from the experimentally coalified peat and wood were comparable to yields of lignin phenols from Miocene Indonesian lignite and coalified wood. Changes in syringyl/vanillyl and p-hydroxy/vanillyl ratios suggest direct demethoxylation as a secondary process to demethylation of methoxyl groups during early coalification, and changes in lignin phenol yields and acid/aldehyde ratios point to a coupling between demethoxylation processes and reactions in the alkyl side chain bonds of the ??-carbon in lignin phenols.

  17. Inhibitory bacteria reduce fungi on early life stages of endangered Colorado boreal toads (Anaxyrus boreas)

    PubMed Central

    Kueneman, Jordan G; Woodhams, Douglas C; Van Treuren, Will; Archer, Holly M; Knight, Rob; McKenzie, Valerie J

    2016-01-01

    Increasingly, host-associated microbiota are recognized to mediate pathogen establishment, providing new ecological perspectives on health and disease. Amphibian skin-associated microbiota interact with the fungal pathogen, Batrachochytrium dendrobatidis (Bd), but little is known about microbial turnover during host development and associations with host immune function. We surveyed skin microbiota of Colorado's endangered boreal toads (Anaxyrus boreas), sampling 181 toads across four life stages (tadpoles, metamorphs, subadults and adults). Our goals were to (1) understand variation in microbial community structure among individuals and sites, (2) characterize shifts in communities during development and (3) examine the prevalence and abundance of known Bd-inhibitory bacteria. We used high-throughput 16S and 18S rRNA gene sequencing (Illumina MiSeq) to characterize bacteria and microeukaryotes, respectively. Life stage had the largest effect on the toad skin microbial community, and site and Bd presence also contributed. Proteobacteria dominated tadpole microbial communities, but were later replaced by Actinobacteria. Microeukaryotes on tadpoles were dominated by the classes Alveolata and Stramenopiles, while fungal groups replaced these groups after metamorphosis. Using a novel database of Bd-inhibitory bacteria, we found fewer Bd-inhibitory bacteria in post-metamorphic stages correlated with increased skin fungi, suggesting that bacteria have a strong role in early developmental stages and reduce skin-associated fungi. PMID:26565725

  18. Organophosphorus pesticides effect on early stages of the axolotl Ambystoma mexicanum (Amphibia: Caudata).

    PubMed

    Robles-Mendoza, C; García-Basilio, C; Cram-Heydrich, S; Hernández-Quiroz, M; Vanegas-Pérez, C

    2009-02-01

    Ambystoma mexicanum is an endemic salamander of Xochimilco, a wetland of the basin of Mexico valley. Nowadays, axolotl populations are decreasing due environmental stressors. Particularly, studies about organophosphorus pesticides (OPPs; i.e. chlorpyrifos and malathion) toxicity are of great importance due to their intensive use in agricultural activities in Xochimilco. Thus, the aim of this study was to evaluate under controlled conditions the toxicity of chlorpyrifos (CPF) and malathion (MLT) on embryos and larvae (stage 44 and 54) of A. mexicanum. Embryos and larvae were exposure 96h from 0.5 to 3mg CPFL(-1) and from 10 to 30mg MLTL(-1) in independent tests. Embryos at the end of this period were maintained 9d without pesticide in order to identify possible recuperation. Differences obtained in mortality, hatching success, development, morphological abnormalities, behaviour and activity, suggest that toxicity of CPF and MLT differs in embryos and larval stages. Embryos were less sensitive to OPPs acute exposure than axolotl larvae; additionally, toxicity of CPF in larval stages was greater than MLT. On the other hand, data obtained in axolotl embryos during the period of recuperation to CPF in particular as delay and inhibition of development, malformations and success of hatching, indicated that these responses turned out more sensitive than mortality. This study allowed to identify the toxicological potential of OPPs on early developmental stages of A. mexicanum and it is a valuable contribution for the future management of the axolotl wild population.

  19. Facial affect recognition in early and late-stage schizophrenia patients.

    PubMed

    Romero-Ferreiro, María Verónica; Aguado, Luis; Rodriguez-Torresano, Javier; Palomo, Tomás; Rodriguez-Jimenez, Roberto; Pedreira-Massa, José Luis

    2016-04-01

    Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps<.01) and an increased misattribution of emotional meaning to neutral faces. PANSS scores of FEP patients on Depressed factor correlated positively with the accuracy to recognize fearful expressions (r=.473). For the MES group fear recognition correlated positively with negative PANSS factor (r=.498) and recognition of sad and neutral expressions was inversely correlated with disorganized PANSS factor (r=-.461 and r=-.541, respectively). These results provide evidence that a generalized impairment of affect recognition is observed in advanced-stage patients and is not characteristic of the early stages of schizophrenia. Moreover, the finding that anomalous attribution of emotional meaning to neutral faces is observed only in MES patients suggests that an increased attribution of salience to social stimuli is a characteristic of social cognition in advanced stages of the disorder.

  20. Susceptibility of some vertebrate hosts to infection with early third-stage larvae of Gnathostoma hispidum.

    PubMed

    Sohn, W M; Lee, S H

    1997-09-01

    Susceptibility of some vertebrates was examined to the early third-stage larvae (EL3) of Gnathostoma hispidum. The larvae collected from the Chinese loaches were infected to 4 silk carps, 3 snake heads, 3 bullfrogs, 5 mice and 9 albino rats. No worms were detected in fish, silk carps and snake heads. In 3 bullfrogs fed 30 larvae, a total of 9 EL3 was recovered in the gastrointestinal tract (8 larvae) and liver (one). In 5 mice infected with 50 larvae, a total of 37 (74.0%) advanced third-stage larvae (AdL3) was recovered from the muscle (31 larvae), liver (5 larvae) and kidney at 4 weeks after infection. In 9 albino rats infected with 115 larvae, a total of 40 (34.8%) AdL3 was found in the muscle. The mammalian hosts were found susceptible to the EL3 of G. hispidum from Chinese loaches.

  1. Arthroscopic assisted bone grafting for early stages of Kienböck's disease.

    PubMed

    Pegoli, L; Ghezzi, A; Cavalli, E; Luchetti, R; Pajardi, G

    2011-01-01

    Kienböck's disease is known for its difficulty in being diagnosed and treated at early stages; option treatments are few and most of them quite aggressive. The author describes his experience with arthroscopic assisted lunate bone grafting. Three patients with diagnosis of stage I avascular necrosis of the lunate (average age: 45 years), were treated. Before surgical procedure, the patients underwent to a conservative treatment. After harvesting the bone graft from the volar surface of the radius, arthroscopic bone grafting was performed. At an average follow-up of 13.5 months (9-15), all the patients show a normal density of the lunate and no arthritic changes in radiographs. The MRI confirmed the lunate vascularity. The number of patients is definitely small, due also to the rarity of the disease and the difficulty in diagnosis, but, despite the very high learning curve, could be the proper first choice of treatment.

  2. Large scale surface migration of P. aeruginosa at early stages of biofilm formation

    NASA Astrophysics Data System (ADS)

    Gibiansky, Maxsim; Utada, Andy; Zhao, Kun; Xian, Wujing; Wong, Gerard

    2013-03-01

    Pseudomonas aeruginosa is a commonly-studied bacterium which can form biofilms, surface-bound aggregates which display increased resistance to various forms of stress, including a greatly enhanced antibiotic resistance. In the early stages of biofilm formation, free-swimming planktonic cells attach to the surface and form microcolonies, expressing a variety of adhesins and transitioning from reversible to irreversible attachment. By using particle tracking algorithms, we can in principle examine the full motility and division history of all cells in a microcolony. Here, we study the effects of the pel polysaccharides in microcolony formation by investigating how pel impacts the initial stages of biofilm formation by the P. aeruginosa PA14 strain. Specifically, we quantify the phenotypic effects of pel on initial attachment, microcolony formation, and biofilm morphology.

  3. Evaluation of the enhanced permeability and retention effect in the early stages of lymph node metastasis.

    PubMed

    Mikada, Mamoru; Sukhbaatar, Ariunbuyan; Miura, Yoshinobu; Horie, Sachiko; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

    2017-02-17

    Most solid cancers spread to new sites via the lymphatics before hematogenous dissemination. However, only a small fraction of an intravenously administered anti-cancer drug enters the lymphatic system to reach metastatic lymph nodes (LNs). Here, we show that the enhanced permeability and retention (EPR) effect is not induced during the early stages of LN metastasis. Luciferase-expressing tumor cells were injected into the subiliac LN of the MXH10/Mo-lpr/lpr mouse to induce metastasis to the proper axillary LN (PALN). In vivo biofluorescence imaging was used to confirm metastasis induction and to quantify the EPR effect, measured as PALN accumulation of intravenously injected indocyanine green (ICG) liposomes. PALN blood vessel volume changes were measured by contrast-enhanced high-frequency ultrasound imaging. The volume and density of blood vessels in the PALN increased until day 29 after inoculation whereas the LN volume remained constant. ICG retention was first detected on day 29 post-inoculation. While CD31-positive cells increased up to day 29 post-inoculation, α-smooth muscle actin-positive cells were detected on day 29 post-inoculation for the first time. These results suggest that the EPR effect was not induced in the early stages of LN metastasis; therefore, systemic chemotherapy would likely not be beneficial during the early stages of LN metastasis. The development of an alternative drug delivery system, independent of the EPR effect, is required for the treatment of LN metastasis. This article is protected by copyright. All rights reserved.

  4. Frequency of Early-Stage Lymphedema and Risk Factors in Postoperative Patients with Breast Cancer

    PubMed Central

    Soyder, Aykut; Taştaban, Engin; Özbaş, Serdar; Boylu, Şükrü; Özgün, Hedef

    2014-01-01

    Objective Lymphedema is a chronic major complication that is seen frequently post-operatively and has negative effects on quality of life. In our study, determining the early-stage postoperative lymphedema frequency and specifying the risk factors in its development has been aimed. Materials and Methods One hundred one cases that were operated on for breast cancer were evaluated regarding the 12-month control of their clinical specifications, histopathological specifications, and specifications related with the surgical intervention retrospectively. The data related to the parameters envisioned as risk factors were evaluated. Results Lymphedema development was found in 7 (6.9%) out of 101 cases constituting the study group. No significant difference (p>0.05) in terms of lymphedema development was determined among age, body mass index (BMI), chemotherapy (CT), postoperative seroma or infection, mastectomy with the dominant arm, and breast-conserving surgery (BCS), which were evaluated as risk factors. There was a significance (p<0.05) between the other risk factors, which were axillary dissection (AD), number of positive lymph nodes (LN), radiotherapy (RT), the tumor size (T), and lymphedema existence. In every case in which lymphedema was determined, it was seen that there was axillary LN involvement and 15≤LN were ablated in the dissection (p<0.05). Conclusion It is seen that AD, RT applied to the breast cancer patients, and T are important risk factors in early-stage lymphedema development. No early-stage lymphedema development was determined in any of the patients to whom sentinel lymph node dissection (SLND) was applied.

  5. Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

    SciTech Connect

    Torok, Jordan A.; Wu, Yuan; Prosnitz, Leonard R.; Kim, Grace J.; Beaven, Anne W.; Diehl, Louis F.; Kelsey, Chris R.

    2015-05-01

    Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

  6. Early oligomerization stages for the non-amyloid component of α-synuclein amyloid

    NASA Astrophysics Data System (ADS)

    Eugene, Cindie; Laghaei, Rozita; Mousseau, Normand

    2014-10-01

    In recent years, much effort has focused on the early stages of aggregation and the formation of amyloid oligomers. Aggregation processes for these proteins are complex and their non-equilibrium nature makes any experimental study very difficult. Under these conditions, simulations provide a useful alternative for understanding the dynamics of the early stages of oligomerization. Here, we focus on the non-Aβ amyloid component (NAC) of the monomer, dimer, and trimer of α-synuclein, an important 35-residue sequence involved in the aggregation and fibrillation of this protein associated with Parkinson's disease. Using Hamiltonian and temperature replica exchange molecular dynamics simulations combined with the coarse grained Optimized Potential for Efficient peptide structure Prediction potential, we identify the role of the various regions and the secondary structures for the onset of oligomerization. For this sequence, we clearly observe the passage from α-helix to β-sheet, a characteristic transition of amyloid proteins. More precisely, we find that the NAC monomer is highly structured with two α-helical regions, between residues 2-13 and 19-25. As the dimer and trimer form, β-sheet structures between residues 2-14 and 26-34 appear and rapidly structure the system. The resulting conformations are much more structured than similar dimers and trimers of β-amyloid and amylin proteins and yet display a strong polymorphism at these early stages of aggregation. In addition to its inherent experimental interest, comparison with other sequences shows that NAC could be a very useful numerical model for understanding the onset of aggregation.

  7. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    PubMed

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  8. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  9. Effect of ocean acidification on early life stages of Atlantic herring (Clupea harengus L.)

    NASA Astrophysics Data System (ADS)

    Franke, A.; Clemmesen, C.

    2011-12-01

    Due to atmospheric accumulation of anthropogenic CO2 the partial pressure of carbon dioxide (pCO2) in surface seawater increases and the pH decreases. This process known as ocean acidification might have severe effects on marine organisms and ecosystems. The present study addresses the effect of ocean acidification on early developmental stages, the most sensitive stages in life history, of the Atlantic herring (Clupea harengus L.). Eggs of the Atlantic herring were fertilized and incubated in artificially acidified seawater (pCO2 1260, 1859, 2626, 2903, 4635 μatm) and a control treatment (pCO2 480 μatm) until the main hatch of herring larvae occurred. The development of the embryos was monitored daily and newly hatched larvae were sampled to analyze their morphometrics, and their condition by measuring the RNA/DNA ratios. Elevated pCO2 neither affected the embryogenesis nor the hatch rate. Furthermore the results showed no linear relationship between pCO2 and total length, dry weight, yolk sac area and otolith area of the newly hatched larvae. For pCO2 and RNA/DNA ratio, however, a significant negative linear relationship was found. The RNA concentration at hatching was reduced at higher pCO2 levels, which could lead to a decreased protein biosynthesis. The results indicate that an increased pCO2 can affect the metabolism of herring embryos negatively. Accordingly, further somatic growth of the larvae could be reduced. This can have consequences for the larval fish, since smaller and slow growing individuals have a lower survival potential due to lower feeding success and increased predation mortality. The regulatory mechanisms necessary to compensate for effects of hypercapnia could therefore lead to lower larval survival. Since the recruitment of fish seems to be determined during the early life stages, future research on the factors influencing these stages are of great importance in fisheries science.

  10. Effects of temperature on early-life-history stages of California halibut Paralichthys californicus

    USGS Publications Warehouse

    Gadomski, D.M.; Caddell, S.M.

    1991-01-01

    - Laboratory experiments were conducted to determine how growth and survival of earlylife-history stages of California halibut Pamlichthys californicus are influenced by temperature, and how optimal temperature ranges may change with ontogeny. As halibut developed from eggs to juveniles, highest survival occurred at increasingly higher temperature ranges. Within tolerance limits, growth and development rates of all early-lifehistory stages were directly proportional to temperature. Eggs hatched successfully at 12, 16, and 20°C; at g and 24°C they died prior to embryo formation. Larval survival 17 days after hatching was 23-46% at 16, 20, and 24°C, but almost all larvae died at 12°C after an initial period of high survival. At gOC,larvai development ceased at the early yolksac stage. Survival of 3-month-old juvenile halibut was significantly greater at 20, 24. and 28°C (57-76°70) than at 16°C (31%). Temperature also affected settlement rate; when the temperature of I-month-old larvae was raised from 16°C to 20°C, settlement occurred about a week sooner than settlement of larvae remaining at 16°C. Tolerance ranges of halibut earlylife-history stages determined in the laboratory approximate temperatures encountered by halibut in the field; high densities of newly-settled halibut larvae and juveniles have been collected in shallow areas of bays where temperatures are often higher than the open ocean inhabited by young larvae. These warmer inshore nursery grounds could enhance growth and survival of halibut juveniles.

  11. Circulating and tissue biomarkers in early-stage non-small cell lung cancer

    PubMed Central

    Fumagalli, Caterina; Bianchi, Fabrizio; Raviele, Paola Rafaniello; Vacirca, Davide; Bertalot, Giovanni; Rampinelli, Cristiano; Lazzeroni, Matteo; Bonanni, Bernardo; Veronesi, Giulia; Fusco, Nicola; Barberis, Massimo; Guerini-Rocco, Elena

    2017-01-01

    Objective We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). Materials and Methods Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test). Promoter methylation status of p16, RASSF1a and RARβ2 and telomerase activity were assessed in sputum samples. DNA was extracted from each tumour developed during follow-up and subjected to a mutation survey using the LungCarta panel on the Sequenom MassARRAY platform. Results During follow-up (9 years) six individuals underwent surgery for stage I NSCLC with a median time of disease onset of 20.5 months. MiR-Test scores were positive (range: 0.14–7.24) in four out of six baseline pre-disease onset sera. No association was identified between free circulating DNA or sputum biomarkers and disease onset. All tumours harboured at least one somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1), and TP53 (n = 3). Conclusion Circulating miRNA tests may represent valuable tools to detect clinically-silent tumours. Early-stage lung adenocarcinomas harbour recurrent genetic events similar to those described in advanced-stage NSCLCs. PMID:28194229

  12. Biopsy Findings After Breast Conservation Therapy for Early-Stage Invasive Breast Cancer

    SciTech Connect

    Vapiwala, Neha Starzyk, Jill; Harris, Eleanor E.; Tchou, Julia C.; Boraas, Marcia C.; Czerniecki, Brian J.; Rosato, Ernest F.; Orel, Susan G.; Solin, Lawrence J.

    2007-10-01

    Purpose: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. Methods and Materials: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. Results: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if {>=}51 years, 57% if 36-50 years, and 83% if {<=}35 years (p = 0.05). The PBR correlated directly with the interval after radiotherapy: 49% if {<=}60 months, 59% if 60.1-120 months, 77% if 120.1-180 months, and 100% if >180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p {>=} 0.15). Conclusion: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.

  13. 'Making the best you can of it': living with early-stage Alzheimer's disease.

    PubMed

    Macrae, Hazel

    2008-04-01

    Drawing upon data from a qualitative study of persons who are in the early stage of the condition, this paper examines the meaning of Alzheimer's disease. It contrasts the meaning of the disease as portrayed in popular culture with its meaning as interpreted by persons living with it. Findings show that persons with the illness do not necessarily accept the negative cultural meaning of the disease, nor the helpless 'victim' role in which they are generally cast. With a determination to 'make the best of it', strategies such as humour, normalisation, present-time orientation, and life review are employed to create a meaningful life.

  14. Clean Energy Finance: Challenges and Opportunities of Early-Stage Energy Investing (Presentation)

    SciTech Connect

    Heap, D.; Pless, J.; Aieta, N.

    2013-12-01

    Characterized by a changing landscape and new opportunities, today's increasingly complex energy decision space will need innovative financing and investment models to appropriately assess risk and profitability. This report provides an overview of the current state of clean energy finance across the entire spectrum but with a focus on early stage investing, and it includes insights from investors across all investment classes. Further, this report aims to provide a roadmap with the mechanisms, limitations, and considerations involved in making successful investments by identifying risks, challenges, and opportunities in the clean energy sector.

  15. A Model of Isotope Separation in Cells at the Early Stages of Evolution.

    PubMed

    Melkikh, A V; Bokunyaeva, A O

    2016-03-01

    The separation of the isotopes of certain ions can serve as an important criterion for the presence of life in the early stages of its evolution. A model of the separation of isotopes during their transport through the cell membrane is constructed. The dependence of the selection coefficient on various parameters is found. In particular, it is shown that the maximum efficiency of the transport of ions corresponds to the minimum enrichment coefficient. At the maximum enrichment, the efficiency of the transport system approaches ½. Calculated enrichment coefficients are compared with experimentally obtained values for different types of cells, and the comparison shows a qualitative agreement between these quantities.

  16. Origin of the Directed Movement of Protocells in the Early Stages of the Evolution of Life

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.; Chesnokova, Oksana I.

    2012-08-01

    The origin of the directed motion of protocells during the early stages of evolution was discussed. The expenditures for movement, space orientation, and reception of information about the environment were taken into consideration, and it was shown that directed movement is evolutionarily advantageous in the following cases: when opposite gradients of different resources (for example, matter and energy) are great enough and when there is a rapid change in environmental parameters. It was also shown that the advantage of directed movement strategies depends greatly on how information about the environment is obtained by a protocell.

  17. Histopathologic findings of spontaneous osteonecrosis of the knee at an early stage: a case report.

    PubMed

    Hatanaka, Hiroyuki; Yamamoto, Takuaki; Motomura, Goro; Sonoda, Kazuhiko; Iwamoto, Yukihide

    2016-05-01

    We histopathologically examined a surgically resected full specimen obtained from an early-stage spontaneous osteonecrosis of the knee (SPONK). On a mid-coronal cut section of the resected medial femoral condyle, a linear fracture line paralleling the subchondral bone endplate was found. Histopathologically, prominent callus formation was seen comprising of reactive woven bone and granulation tissue on both sides of the fracture. Fracture-related bone debris was focally observed at the osteochondral side of the fracture. Definitive features of antecedent bone infarction such as creeping substitution and bone marrow necrosis were not detected. These findings suggested that SPONK was the result of a subchondral fracture rather than primary osteonecrosis.

  18. Early-Stage Folding in Proteins (In Silico) Sequence-to-Structure Relation

    PubMed Central

    2005-01-01

    A sequence-to-structure library has been created based on the complete PDB database. The tetrapeptide was selected as a unit representing a well-defined structural motif. Seven structural forms were introduced for structure classification. The early-stage folding conformations were used as the objects for structure analysis and classification. The degree of determinability was estimated for the sequence-to-structure and structure-to-sequence relations. Probability calculus and informational entropy were applied for quantitative estimation of the mutual relation between them. The structural motifs representing different forms of loops and bends were found to favor particular sequences in structure-to-sequence analysis. PMID:16046811

  19. Influence of secondary structure on recovery from pauses during early stages of RNA transcription.

    PubMed

    Klopper, A V; Bois, J S; Grill, S W

    2010-03-01

    The initial stages of transcription by RNA polymerase are frequently marked by pausing and stalling events. These events have been linked to an inactive backtracked state in which the polymerase diffuses along the template DNA. We investigate theoretically the influence of RNA secondary structure in confining this diffusion. The effective confinement length peaks at transcript lengths commensurate with early stalling. This finite-size effect accounts for slow progress at the beginning of transcription, which we illustrate via stochastic hopping models for backtracking polymerases.

  20. Influence of secondary structure on recovery from pauses during early stages of RNA transcription

    NASA Astrophysics Data System (ADS)

    Klopper, A. V.; Bois, J. S.; Grill, S. W.

    2010-03-01

    The initial stages of transcription by RNA polymerase are frequently marked by pausing and stalling events. These events have been linked to an inactive backtracked state in which the polymerase diffuses along the template DNA. We investigate theoretically the influence of RNA secondary structure in confining this diffusion. The effective confinement length peaks at transcript lengths commensurate with early stalling. This finite-size effect accounts for slow progress at the beginning of transcription, which we illustrate via stochastic hopping models for backtracking polymerases.

  1. Nonlinear Langevin model for the early-stage dynamics of electrospinning jets

    NASA Astrophysics Data System (ADS)

    Lauricella, Marco; Pontrelli, Giuseppe; Pisignano, Dario; Succi, Sauro

    2015-09-01

    We present a nonlinear Langevin model to investigate the early-stage dynamics of electrified polymer jets in electrospinning experiments. In particular, we study the effects of air drag force on the uniaxial elongation of the charged jet, right after ejection from the nozzle. Numerical simulations show that the elongation of the jet filament close to the injection point is significantly affected by the nonlinear drag exerted by the surrounding air. These results provide useful insights for the optimal design of current and future electrospinning experiments.

  2. Effects of Offshore Wind Farms on the Early Life Stages of Dicentrarchus labrax.

    PubMed

    Debusschere, Elisabeth; De Coensel, Bert; Vandendriessche, Sofie; Botteldooren, Dick; Hostens, Kris; Vincx, Magda; Degraer, Steven

    2016-01-01

    Anthropogenically generated underwater noise in the marine environment is ubiquitous, comprising both intense impulse and continuous noise. The installation of offshore wind farms across the North Sea has triggered a range of ecological questions regarding the impact of anthropogenically produced underwater noise on marine wildlife. Our interest is on the impact on the "passive drifters," i.e., the early life stages of fish that form the basis of fish populations and are an important prey for pelagic predators. This study deals with the impact of pile driving and operational noise generated at offshore wind farms on Dicentrarchus labrax (sea bass) larvae.

  3. A case of painless thyroiditis in a very early stage of pregnancy.

    PubMed

    Sato, Shiori; Endo, Kei; Iizaka, Toru; Saiki, Ryo; Iwaku, Kenji; Sato, Shotaro; Takahashi, Yasuyoshi; Otsuka, Fumiko; Taniyama, Matsuo

    2012-01-01

    We report a case of painless thyroiditis detected during the first trimester of pregnancy. A 29-year-old Japanese woman was hospitalized because of thyrotoxicosis and she was confirmed to be pregnant. The gestational age was 4 weeks. Blood examinations revealed negative TSH receptor antibodies, however, we started potassium iodide because we were unable to rule out Graves' disease. Thyroid hormone levels were normalized in 3 weeks and remained low even after discontinuation of medication. She received replacement therapy with levothyroxine sodium hydrate till 3 months after delivery. Painless thyroiditis can be one of the differential diagnoses of thyrotoxicosis in a very early stage of pregnancy.

  4. Impact of [{sup 18}F] Fluorodeoxyglucose Positron Emission Tomography on Staging and Management of Early-Stage Follicular Non-Hodgkin Lymphoma

    SciTech Connect

    Wirth, Andrew Foo, Marcus; Seymour, John F.; MacManus, Michael P.; Hicks, Rodney J.

    2008-05-01

    Purpose: Accurate staging is critical to select patients with early-stage (I-II) follicular lymphoma (ESFL) suitable for involved-field radiotherapy (IFRT) and to define the radiotherapy portal. We evaluated the impact of fluorodeoxyglucose (FDG) PET on staging, treatment, and outcome for patients with ESFL on conventional staging. Methods and Materials: Forty-two patients with untreated ESFL (World Health Organization Grade I-IIIa, or 'low grade') following a minimum of physical examination, computerized tomography, and bone marrow examination (conventional assessment) and who had staging PET from June 1997 to June 2006 were studied retrospectively. Stage allocation was based on routine imaging reports. Disease sites, stage, and management plan were recorded based on conventional assessment or conventional assessment plus PET. Results: FDG avidity was demonstrated in 97% of patients in whom disease was evident on conventional assessment after biopsy. PET findings suggested a change of stage or management in 19 patients: 13 (31%) who were upstaged to Stage III-IV, altering ideal management from IFRT to systemic therapy, and 6 (14%) who had the involved field enlarged, including 4 upstaged from Stage I to II. Of these 19 cases, PET findings were considered true positive in 8 patients, indeterminate in 10, and false positive in only 1 patient. Conclusions: Our data confirm that ESFL is usually FDG-avid. In routine practice, PET has the potential to upstage and thereby alter management in a high proportion of patients with apparent ESFL.

  5. Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse

    SciTech Connect

    Xu Fang; Ji Jian; Li Li; Chen Rong; Hu Weicheng . E-mail: huweicheng@sdu.edu.cn

    2007-01-19

    The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.

  6. Selective attention to signs of success: social dominance and early stage interpersonal perception.

    PubMed

    Maner, Jon K; DeWall, C Nathan; Gailliot, Matthew T

    2008-04-01

    Results from two experiments suggest that observers selectively attend to male, but not female, targets displaying signs of social dominance. Participants overestimated the frequency of dominant men in rapidly presented stimulus arrays (Study 1) and visually fixated on dominant men in an eyetracking experiment (Study 2). When viewing female targets, participants attended to signs of physical attractiveness rather than social dominance. Findings fit with evolutionary models of mating, which imply that dominance and physical attractiveness sometimes tend to be prioritized preferentially in judgments of men versus women, respectively. Findings suggest that sex differences in human mating are observed not only at the level of overt mating preferences and choices but also at early stages of interpersonal perception. This research demonstrates the utility of examining early-in-the-stream social cognition through the functionalist lens of adaptive thinking.

  7. The relationship between cortisol and verbal memory in the early stages of Huntington's disease.

    PubMed

    Shirbin, Christopher A; Chua, Phyllis; Churchyard, Andrew; Hannan, Anthony J; Lowndes, Georgia; Stout, Julie C

    2013-03-01

    Hypothalamic pituitary adrenal (HPA) axis hyperactivity has been linked to learning and memory difficulties in a range of neurodegenerative and neuropsychiatric conditions. In Huntington's disease (HD), both declines in learning and memory and HPA axis dysfunction are present early in the disease. However, the relationship between specific learning and memory deficits and HPA axis functioning in HD has not been examined. The aim of this study was to investigate cortisol levels in relation to verbal learning and memory in pre-diagnosed (pre-HD) participants and patients at the early stages of diagnosed HD (early-HD). Cortisol concentration was assayed in saliva samples from 57 participants (17 early-HD, 20 pre-HD, and 20 controls) at four time-points across a 24-h period. Verbal memory was assessed using the California Verbal Learning Test-Second Edition (CVLT-II). We focused statistical analyses on the late evening cortisol concentration, and examined cortisol levels and verbal memory function in relation to diagnostic group (control, pre-HD, early-HD), and in a separate set of analyses combining pre-HD and early-HD (and excluding controls) we also examined cortisol and verbal memory performance in relation to the severity of HD-related motor signs. Of these two classification approaches, HD motor sign severity was more strongly associated with high evening cortisol levels and both reduced information encoding and memory retrieval. Separately, there was also a trend of higher cortisol levels in pre-HD. The findings suggest hypercortisolism and the underlying pathological changes may begin many years before a clinical diagnosis is made, but the memory decline associated with HPA axis disturbance may only become detectable once motor signs become pronounced.

  8. Parallel processing of general and specific threat during early stages of perception

    PubMed Central

    2016-01-01

    Differential processing of threat can consummate as early as 100 ms post-stimulus. Moreover, early perception not only differentiates threat from non-threat stimuli but also distinguishes among discrete threat subtypes (e.g. fear, disgust and anger). Combining spatial-frequency-filtered images of fear, disgust and neutral scenes with high-density event-related potentials and intracranial source estimation, we investigated the neural underpinnings of general and specific threat processing in early stages of perception. Conveyed in low spatial frequencies, fear and disgust images evoked convergent visual responses with similarly enhanced N1 potentials and dorsal visual (middle temporal gyrus) cortical activity (relative to neutral cues; peaking at 156 ms). Nevertheless, conveyed in high spatial frequencies, fear and disgust elicited divergent visual responses, with fear enhancing and disgust suppressing P1 potentials and ventral visual (occipital fusiform) cortical activity (peaking at 121 ms). Therefore, general and specific threat processing operates in parallel in early perception, with the ventral visual pathway engaged in specific processing of discrete threats and the dorsal visual pathway in general threat processing. Furthermore, selectively tuned to distinctive spatial-frequency channels and visual pathways, these parallel processes underpin dimensional and categorical threat characterization, promoting efficient threat response. These findings thus lend support to hybrid models of emotion. PMID:26412811

  9. Macrophage migration inhibitory factor (MIF): genetic evidence for participation in early onset and early stage rheumatoid arthritis

    PubMed Central

    Llamas-Covarrubias, MA; Valle, Y; Bucala, R; Navarro-Hernández, RE; Palafox-Sánchez, CA; Padilla-Gutiérrez, JR; Parra-Rojas, I; Bernard-Medina, AG; Reyes-Castillo, Z; Muñoz-Valle, JF

    2013-01-01

    Macrophage migration inhibitory factor (MIF) is an upstream pro-inflammatory cytokine that is associated with the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis (RA).Two polymorphisms in the upstream region exist in the MIF gene and are associated with RA susceptibility or severity in different populations. In this case-control study, we investigated whether MIF polymorphisms are associated with RA susceptibility or activity in a western Mexican population .The relationship of MIF levels with clinical features of disease also was assessed. Genotyping of the -794 CATT5-8(rs5844572) and the -173 G>C (s755622) polymorphisms was performed by PCR and PCR-RFLP respectively on 226 RA patients and 210 healthy subjects. Serum MIF levels were determined by ELISA. We found a significant association between the -794 CATT5-8 6,7 MIF genotype with RA. Moreover, we detected an association between the -794 CATT7 allele with early onset RA. The -794 CATT7 and -173*C alleles, which are in linkage disequilibrium, were associated with high disease activityon RA patients. A positive correlation between circulating MIF levels and C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, anti-citrullinated protein/peptides antibodies and TNFα was detected. MIF levels appear to be associated with disease progression rather than disease activity, which is distinct from the established relationship between disease activity and TNFα levels. In conclusion, the MIF gene and protein are associated with RA in a western Mexican population, with a main contribution onto early onset and early stages of disease. PMID:23402792

  10. Early results of neurodevelopment following hybrid stage I for hypoplastic left heart syndrome.

    PubMed

    Cheatham, Sharon L; Carey, Helen; Chisolm, Joanne L; Heathcock, Jill C; Steward, Deborah

    2015-03-01

    Motor skills and neurodevelopment in infants with hypoplastic left heart syndrome (HLHS) who have undergone Hybrid Stage I palliation is unknown. The purpose of this study is to assess early neurodevelopment in infants with HLHS after Hybrid Stage I palliation. Developmental assessment was performed in HLHS infants who underwent Hybrid Stage I palliation at 2 and 4 months of age using the Test of Infant Motor Performance, and at 6 months of age, prior to undergoing the second staged surgery, using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Results were compared to healthy control subjects and norm-referenced data. The HLHS group scored between -1 and -2 standard deviations (SD) below the mean at 2 months of age (p = 0.002), and within -1 SD of the mean, at 4 months of age (p = 0.0019), on the TIMP. Compared to the control group, composite motor skills were significantly lower at 6 months of age on the Bayley-III in the HLHS group (p = 0.0489), however, not significant for cognitive (p = 0.29) or language (p = 0.68). Percentile rank motor scores were 17 ± 20 % in the HLHS group compared to 85 ± 12 % for the healthy age-matched control group. Infants with HLHS who undergo Hybrid Stage I palliation score lower on standardized motor skill tests compared to healthy age-matched controls and the norm-referenced population. This suggests that infants with HLHS have poorer motor skill performance than typically developing infants at 6 months of age.

  11. Development of cryopreservation protocols for early stage zebrafish (Danio rerio) ovarian follicles using controlled slow cooling.

    PubMed

    Tsai, S; Rawson, D M; Zhang, T

    2009-05-01

    Cryopreservation of germplasm of aquatic species offers many benefits to the fields of aquaculture, conservation and biomedicine. Although successful fish sperm cryopreservation has been achieved with many species, there has been no report of successful cryopreservation of fish embryos and late stage oocytes which are large, chilling sensitive and have low membrane permeability. In the present study, cryopreservation of early stage zebrafish ovarian follicles was studied for the first time using controlled slow freezing. The effect of cryoprotectant, freezing medium, cooling rate, method for cryoprotectant removal, post-thaw incubation time and ovarian follicle developmental stage were investigated. Stages I and II ovarian follicles were frozen in 4M methanol and 3M DMSO in either L-15 medium or KCl buffer. Ovarian follicle viability was assessed using trypan blue, FDA+PI staining and ADP/ATP assay. The results showed that KCl buffer was more beneficial than L-15 medium, methanol was more effective than DMSO, optimum cooling rates were 2-4 degrees C/min, stepwise removal of cryoprotectant improved ovarian follicle viability significantly and stage I ovarian follicles were more sensitive to freezing. The results also showed that FDA+PI staining and ADP/ATP assay were more sensitive than TB staining. The highest follicle viabilities after post-thaw incubation for 2h obtained with FDA+PI staining were 50.7+/-4.0% although ADP/ATP ratios of the cryopreserved follicles were significantly increased indicating increased cell damage. Studies are currently being carried out on in vitro maturation of these cryopreserved ovarian follicles.

  12. Targeted labeling of an early-stage tumor spheroid in a chorioallantoic membrane model with upconversion nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Holz, Jasmin A.; Ding, Yadan; Liu, Xiaomin; Zhang, Youlin; Tu, Langping; Kong, Xianggui; Priem, Bram; Nadort, Annemarie; Lambrechts, Saskia A. G.; Aalders, Maurice C. G.; Buma, Wybren Jan; Liu, Yichun; Zhang, Hong

    2015-01-01

    In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb).In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb). Electronic supplementary information (ESI) available: Details of experimental procedures for the sample preparation and characterization, Chick CAM model, 3-D multicellular tumor spheroids, UCNPs circulating in CAM. See DOI: 10.1039/c4nr05638h

  13. Effect of light Sphagnum peat on odour formation in the early stages of biowaste composting.

    PubMed

    Kurola, Jukka M; Arnold, Mona; Kontro, Merja H; Talves, Matti; Romantschuk, Martin

    2010-05-01

    In the present study, we investigated the effects of two bulking materials, Sphagnum peat and pine wood chips, on the early stages of biowaste composting in two pilot-scale processes. Emphasis was placed on studying the formation conditions of malodorous compost gases in the initial phases of the processes. The results showed that gas emission leaving an open windrow and a closed drum composting system contained elevated concentrations of fermentative microbial metabolites when acid Sphagnum peat (pH 3.2) was used as a bulking material. Moreover, the gas emission of the peat amended drum composter contained a high concentration of odour (up to 450,000oum(-3) of air). The highest odour values in the outlet gas of peat amended composts coincided with the elevated concentrations of volatile organic compounds such as acetoin and buthanedion. We conclude that the acidifying qualities of composting substrates or bulking material may intensify odour emission from biowaste composts and prolong the early stages of the composting process.

  14. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775–875 cm‑1, lectins at 1003, 1238, 1340, 1449 and 1672 cm‑1, DNA in the region 1040–1140 cm‑1 and alpha and beta structures of proteins in the region 933–967 cm‑1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  15. Embryotoxicity of nitrophenols to the early life stages of zebrafish (Danio rerio).

    PubMed

    Ceylan, Zeynep; Şişman, Turgay; Yazıcı, Zehra; Altıkat, Aysun Özen

    2016-08-01

    The nitrophenols (NPs) are water-soluble compounds. These compounds pose a significant health threat since they are priority environmental pollutants. In this study, 2-Nitrophenol (2NP) and 2,4-dinitrophenol (DNP) were examined for embryo and early life stage toxicity in zebrafish (Danio rerio). Acute toxicity and teratogenicity of 2NP and DNP were tested for 4 days using zebrafish embryos. The typical lesions observed were no somite formation, incomplete eye and head development, tail curvature, weak pigmentation (≤48 hours postfertilization (hpf)), kyphosis, scoliosis, yolk sac deformity, and nonpigmentation (72 hpf). Also, embryo and larval mortality increased and hatching success decreased. The severity of abnormalities and mortalities were concentration- and compound-dependent. Of the compounds tested, 2,4-DNP was found to be highly toxic to the fish embryos following exposure. The median lethal concentrations and median effective concentrations for 2NP are 18.7 mg/L and 7.9 mg/L, respectively; the corresponding values for DNP are 9.65 mg/L and 3.05 mg/L for 48 h. The chorda deformity was the most sensitive endpoint measured. It is suggested that the embryotoxicity may be mediated by an oxidative phosphorylation uncoupling mechanism. This article is the first to describe the teratogenicity and embryotoxicity of two NPs to the early life stages of zebrafish.

  16. Genetic identification of female Cannabis sativa plants at early developmental stage.

    PubMed

    Techen, Natascha; Chandra, Suman; Lata, Hemant; Elsohly, Mahmoud A; Khan, Ikhlas A

    2010-11-01

    Sequence-characterized amplified region (SCAR) markers were used to identify female plants at an early developmental stage in four different varieties of Cannabis sativa. Using the cetyl trimethylammonium bromide (CTAB) method, DNA was isolated from two-week-old plants of three drug-type varieties (Terbag W1, Terbag K2, and Terbag MX) and one fiber-type variety (Terbag Fedora A7) of C. sativa grown under controlled environmental conditions through seeds. Attempts to use MADC2 (male-associated DNA from Cannabis sativa) primers as a marker to identify the sex of Cannabis sativa plants were successful. Amplification of genomic DNA using MADC2-F and MADC2-R primers produced two distinct fragments, one with a size of approximately 450 bp for female plants and one for male plants with a size of approximately 300 bp. After harvesting the tissues for DNA extraction, plants were subjected to a flowering photoperiod (i.e., 12-h light cycle), and the appearance of flowers was compared with the DNA analysis. The results of the molecular analysis were found to be concordant with the appearance of male or female flowers. The results of this study represent a quick and reliable technique for the identification of sex in Cannabis plants using SCAR markers at a very early developmental stage.

  17. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

    2015-01-01

    One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

  18. Neck circumference and early stage atherosclerosis: the cardiometabolic risk in Chinese (CRC) study

    PubMed Central

    2014-01-01

    Background Neck circumference (NC) has been previously related to cardiometabolic risk factors. In this study we examined the association between NC and early stage atherosclerosis in Chinese adults. Methods The study samples were from a community-based health examination survey in central China. In total 2,318 men and women (18-64 y) were included in the final analyses. Carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and NC were measured. Results After adjustment for age, sex, lipids, glucose, blood pressure, heart rate, body mass index (BMI), high NC was significantly associated with an increasing trend of cfPWV, cdPWV and crPWV (P = 0.001, 0.049, and 0.038; respectively). In addition, we found significant interaction between hypertension status and NC level in relation to cfPWV, adjusted for age, sex, BMI, fasting glucose, lipids and heart rate(P for interaction = 0.034). The associations between NC and cfPWV were significant (P = 0.02) among those with hypertension, but not significant among those without hypertension. Conclusions Our data showed that high NC was associated with an increased risk of early stage atherosclerosis in Chinese adults, independent of other metabolic risk factors. Hypertension might modify the association between NC and cfPWV. PMID:25001365

  19. Early-Stage Capital Cost Estimation of Biorefinery Processes: A Comparative Study of Heuristic Techniques.

    PubMed

    Tsagkari, Mirela; Couturier, Jean-Luc; Kokossis, Antonis; Dubois, Jean-Luc

    2016-09-08

    Biorefineries offer a promising alternative to fossil-based processing industries and have undergone rapid development in recent years. Limited financial resources and stringent company budgets necessitate quick capital estimation of pioneering biorefinery projects at the early stages of their conception to screen process alternatives, decide on project viability, and allocate resources to the most promising cases. Biorefineries are capital-intensive projects that involve state-of-the-art technologies for which there is no prior experience or sufficient historical data. This work reviews existing rapid cost estimation practices, which can be used by researchers with no previous cost estimating experience. It also comprises a comparative study of six cost methods on three well-documented biorefinery processes to evaluate their accuracy and precision. The results illustrate discrepancies among the methods because their extrapolation on biorefinery data often violates inherent assumptions. This study recommends the most appropriate rapid cost methods and urges the development of an improved early-stage capital cost estimation tool suitable for biorefinery processes.

  20. Divergent natural selection promotes immigrant inviability at early and late stages of evolutionary divergence.

    PubMed

    Ingley, Spencer J; Johnson, Jerald B

    2016-03-01

    Natural selection's role in speciation has been of fundamental importance since Darwin first outlined his theory. Recently, work has focused on understanding how selection drives trait divergence, and subsequently reproductive isolation. "Immigrant inviability," a barrier that arises from selection against immigrants in their nonnative environment, appears to be of particular importance. Although immigrant inviability is likely ubiquitous, we know relatively little about how selection acts on traits to drive immigrant inviability, and how important immigrant inviability is at early-versus-late stages of divergence. We present a study evaluating the role of predation in the evolution of immigrant inviability in recently diverged population pairs and a well-established species pair of Brachyrhaphis fishes. We evaluate performance in a high-predation environment by assessing survival in the presence of a predator, and swimming endurance in a low-predation environment. We find strong signatures of local adaptation and immigrant inviability of roughly the same magnitude both early and late in divergence. We find remarkably conserved selection for burst-speed swimming (important in predator evasion), and selection for increased size in low-predation environments. Our results highlight the consistency with which selection acts during speciation, and suggest that similar factors might promote initial population differentiation and maintain differentiation at late stages of divergence.

  1. [GABA--the basic mediator of excitation in the early stages of hippocampal development].

    PubMed

    Khazipov, R N; Zefirov, A L; Ben-Ari, E

    1998-01-01

    GABA is the principal neurotransmitter of inhibition in the adult mammalian brain. However, at early stages of development, including embryonic period and first week of postnatal life, GABA plays the role of main neurotransmitter of excitation. The paradoxical excitatory effect of GABA is due to an inversed chloride gradient and therefore a depolarizing direction of GABA-A receptor mediated responses. In addition, another type of GABAergic inhibition mediated by postsynaptic GABA-B receptors is not functional at early stage of life. In the neonatal rat hippocampus, GABA, acting via GABA-A receptors, activates voltage gated sodium and calcium channels and potentiates the activity of NMDA receptors by reducing their voltage dependent Mg2+ block. The temporal window when GABA exerts excitatory actions coincides with a particular pattern of activity of hippocampal neuronal network that is characterized by periodical giant depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform discharges. Recent studies have shown that GDPs result from the synchronous discharge of GABAergic interneurons and principal glutamatergic pyramidal cells and are mediated by the synergistic excitatory actions of GABA-A and glutamate receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may therefore be implicated in hebbian modulation of developing synapses and activity-dependent formation of the hippocampal network.

  2. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy.

    PubMed

    Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul

    2010-03-01

    The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg.

  3. Prenatal sonography in hydranencephaly: findings during the early stages of disease.

    PubMed

    Sepulveda, Waldo; Cortes-Yepes, Hernan; Wong, Amy E; Dezerega, Victor; Corral, Edgardo; Malinger, Gustavo

    2012-05-01

    The purpose of this report is to describe the prenatal sonographic findings in fetuses with hydranencephaly diagnosed during the early stages of disease. Four cases with characteristics of hydranencephaly were retrospectively identified from 2 Latin American fetal medicine referral centers. Information on maternal demographics, sonographic findings, antenatal courses, and pregnancy outcomes was retrieved from the ultrasound reports and medical records. Cases were diagnosed between 21 and 23 weeks' gestation. The sonographic findings were similar in all cases and included absent cerebral hemispheres, which were replaced by homogeneous echogenic material filling the supratentorial space, and preservation of the thalami, brain stem, and cerebellum. The head circumference measurement was within the normal range, but the transverse cerebellar diameter was below the fifth percentile in 3 of the 4 cases. A follow-up scan in 1 of these cases demonstrated the classic anechoic fluid-filled appearance of hydranencephaly 2 weeks after diagnosis. Confirmation of the diagnosis was available in 2 cases, by postmortem examination in 1 and by fetal magnetic resonance imaging in the other. No further investigations were performed in the 2 women who opted for termination of pregnancy. In conclusion, during the early stages of disease, hydranencephaly is characterized by the presence of a large intracranial saclike structure containing homogeneous echogenic material, representing blood and necrotic debris secondary to massive liquefaction of the developing cerebral hemispheres.

  4. Robotic Compartment-Based Radical Surgery in Early-Stage Cervical Cancer

    PubMed Central

    Toptas, Tayfun; Uysal, Aysel; Ureyen, Isin; Erol, Onur; Simsek, Tayup

    2016-01-01

    A radical hysterectomy with pelvic lymphadenectomy is the recommended treatment option in patients with early-stage cervical cancer. Although various classifications were developed in order to define the resection margins of this operation, no clear standardization could be achieved both in the nomenclature and in the extent of the surgery. Total mesometrial resection (TMMR) is a novel procedure which aims to remove all components of the compartment formed by Müllerian duct in which female reproductive organs develop. TMMR differs from the conventional radical hysterectomy techniques in that its surgical philosophy, terminology, and partly resection borders are different. In this paper, a TMMR with therapeutic pelvic lymphadenectomy operation that we performed for the first time with robot-assisted laparoscopic (robotic) approach in an early-stage cervical cancer patient was presented. This procedure has already been described in open surgery by Michael Höckel and translated to the robotic surgery by Rainer Kimmig. Our report is the second paper, to our knowledge, to present the initial experience regarding robotic TMMR in the English literature. PMID:27195167

  5. The Management of Early Stage and Metastatic Triple Negative Breast Cancer: A Review

    PubMed Central

    Anders, Carey K.; Zagar, Timothy M.; Carey, Lisa A.

    2013-01-01

    Triple negative breast cancer (TNBC) defined as lacking expression of the estrogen receptor, progesterone receptor and HER2, comprises approximately 15% of incident breast cancers and is over-represented among those with metastatic disease. It is increasingly clear that TNBC is heterogeneous and that there are several biologically distinct subtypes within TNBC, in particular the basal-like subtype but also the claudin-low, among others. While the incidence of BRCA mutations across all subsets of breast cancer is quite low (~5%), BRCA mutations are more common among those with TNBC (~20%) and may have therapeutic implications. The general principles guiding the use of chemotherapy and radiation therapy do not differ dramatically between early stage TNBC and non-TNBC. There is a trend, however, to treat TNBC at a lower stage with chemotherapy as this is the only way to systemically reduce recurrence risk. In the metastatic setting, while cytotoxic chemotherapy is the mainstay of treatment for advanced TNBC, there are many promising targeted therapies in development in both the preclinical and early phase clinical trial settings. While the treatment of TNBC remains a challenge, coordinated efforts between clinician/scientist partnerships providing a comprehensive understanding of TNBC genomic, proteomic and other biologic processes may result in individualized therapy for TNBC faster than other subtypes -- driven by both the heterogeneity we know exists within this clinical entity and the intense need for improved treatment. PMID:23915742

  6. Diagnosis of early-stage esophageal cancer by Raman spectroscopy and chemometric techniques.

    PubMed

    Ishigaki, Mika; Maeda, Yasuhiro; Taketani, Akinori; Andriana, Bibin B; Ishihara, Ryu; Wongravee, Kanet; Ozaki, Yukihiro; Sato, Hidetoshi

    2016-02-07

    Esophageal cancer is a disease with high mortality. In order to improve the 5 year survival rate after cancer treatment, it is important to develop a method for early detection of the cancer and for therapy support. There is increasing evidence that Raman spectroscopy, in combination with chemometric analysis, is a powerful technique for discriminating pre-cancerous and cancerous biochemical changes. In the present study, we used Raman spectroscopy to examine early-stage (stages 0 and I) esophageal cancer samples ex vivo. Comparison between the Raman spectra of cancerous and normal samples using a t-test showed decreased concentrations of glycogen, collagen, and tryptophan in cancerous tissue. Partial least squares regression (PLSR) analysis and self-organization maps (SOMs) discriminated the datasets of cancerous and normal samples into two groups, but there was a relatively large overlap between them. Linear discriminant analysis (LDA) based on Raman bands found in the t-test was able to predict the tissue types with 81.0% sensitivity and 94.0% specificity.

  7. Behavior of homologous chromosomes in early meiotic stages of human spermatocytes as revealed by FISH

    SciTech Connect

    Bar-Am, I.; Avivi, L.; Mukame, E.

    1994-09-01

    The process by which homologous chromosomes recognize each other at the beginning of meiosis, prior to synapsis, is poorly understood. To gain a better understanding as to when, where and how a given chromosome approaches its pairing partner, chromosome behavior at early stages of meiosis in human spermatocytes was studied. Using multi-color FISH with centromeric- and telomeric-specific probes, as well as with whole chromosome DNA libraries, it was clearly aligned. Rather, similarly to non-homologous chromosomes, they were well separated from each other. At the commencement of synapsis, during the process of homology search, homologues underwent a drastic conformational change, elongating into strands that approached each other by their telomeres. Just preceding the co-alignment of the homologous centromeres, telomeres changed their interphase random distribution and occupied a confined region of the nuclear periphery. Following synapsis, telomeres spread over the whole nuclear periphery. These dynamics in the telomeres distribution, which are unique to early stages of meiosis, are presumably related to the role that telomeres play in the process of homology search and the commencement of synapsis.

  8. Marital relationship quality in early-stage dementia: perspectives from people with dementia and their spouses.

    PubMed

    Clare, Linda; Nelis, Sharon M; Whitaker, Christopher J; Martyr, Anthony; Markova, Ivana S; Roth, Ilona; Woods, Robert T; Morris, Robin G

    2012-01-01

    Spouse caregivers of people with dementia (PwD) report relatively poor marital relationship quality (RQ), but few studies have obtained the perspective of the PwD, examined discrepancies between spouses, or considered changes in RQ over time. This study explored caregiver and PwD perceptions of RQ, identified associated factors, and examined changes over an 18-month period. Participants were 54 couples where one spouse had early-stage dementia and 54 were control couples. RQ was assessed with the Positive Affect Index. Measures of mood, stress, and quality of life (QoL) were also administered. The clinical couples were followed up after 9 and 18 months. Caregivers gave significantly lower RQ ratings than controls. PwD ratings did not differ significantly from those of caregivers or controls. Dyadic discrepancies were significantly greater in the clinical than in the control group. Caregiver ratings were associated with stress, whereas PwD ratings were associated with depression and QoL. Discrepancies were associated with caregiver stress and with PwD mood, QoL, and age. Caregiver ratings declined significantly over time; PwD ratings did not decline significantly, but showed different trends for men and women. It is important to consider RQ when considering how to support couples where one partner has early-stage dementia.

  9. Early life-stage toxicity test methods for gulf toadfish (Opsanus beta) and results using chlorpyrifos

    SciTech Connect

    Hansen, D.J.; Goodman, L.R.; Cripe, G.M.; Macauley, S.F.

    1986-02-01

    Gulf toadfish (Opsanus beta) were continuously exposed as embryos, sac fry, and juveniles to technical chlorpyrifos in two 49-day early life-stage toxicity tests. Survival was significantly (alpha = 0.05) reduced only in 150 micrograms/liter. However, toadfish exposed to chlorpyrifos concentrations from 3.7 to 150 micrograms/liter weighted significantly less than control fish: 9% lower in 3.7 micrograms/liter to 62% lower in 150 micrograms/liter. The 96-hr LC50 for juvenile fish was 520 micrograms/liter. Concentrations of chlorpyrifos in toadfish and bioconcentration factors increased with increasing exposure concentration, a condition not generally observed with other marine fishes and other test chemicals. These results demonstrated the procedures for, and the practicality of, early life-stage tests with this marine species. We recommend the use of the gulf toadfish for comparative toxicity testing and for evaluating the toxicity of substances in conjunction with ontogenetical, physiological, and histological investigations of this considerably studied genus. We do not recommend it for routine effects testing.

  10. Neuroprotection of Granulocyte Colony-Stimulating Factor for Early Stage Parkinson's Disease.

    PubMed

    Tsai, Sheng-Tzung; Chu, Sung-Chao; Liu, Shu-Hsin; Pang, Cheng-Yoong; Hou, Ting-Wen; Lin, Shinn-Zong; Chen, Shin-Yuan

    2017-03-13

    Parkinson's disease (PD) is a slowly progressive neurodegenerative disease. Both medical and surgical choices provide symptomatic treatment. Granulocyte colony-stimulating factor (G-CSF), a conventional treatment for hematological diseases, has demonstrated its effectiveness in acute and chronic neurological diseases through its anti-inflammatory and antiapoptosis mechanisms. Based on previous in vitro and in vivo studies, we administered a lower dose (3.3 μg/kg) G-CSF injection for 5 days and six courses for 1 year in early-stage PD patients as a phase I trial. The four PD patient's mean unified PD rating scale motor scores in medication off status remained stable from 23 before the first G-CSF injection to 22 during the 2-year follow-up. 3,4-Dihydroxy-6-18F-fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) studies also revealed an annual 3.5% decrease in radiotracer uptake over the caudate nucleus and 7% in the putamen, both slower than those of previous reports of PD. Adverse effects included transient muscular-skeletal pain, nausea, vomiting, and elevated liver enzymes. Based on this preliminary report, G-CSF seems to alleviate disease deterioration for early stage PD patients. The effectiveness of G-CSF was possibly due to its amelioration of progressive dopaminergic neuron degeneration.

  11. Sham Feeding with Chewing Gum in Early Stage of Acute Pancreatitis: A Randomized Clinical Trial

    PubMed Central

    Jiang, Zongxing; Liang, Hongyin; Huang, Zhu; Tang, Jiajia; Tang, Lijun

    2017-01-01

    Background The correlation between sham feeding and acute pancreatitis (AP) has only been examined in limited studies. We aimed to investigate the efficacy and safety of sham feeding in the early stage of AP. Material/Methods A randomized controlled clinical trial was performed. Equal groups of AP patients were recruited. Patients in the sham feeding group received chewing gum 4 times a day after admission. All patients in the trial received standard treatment consistent with the guidelines for AP. The primary outcomes were mortality, length of stay (LOS), and medical expenses. Secondary outcomes were the incidence of complications and other adverse events, return of gastrointestinal function, the details of enteral nutrition and intra-abdominal pressure. Results From May 2014 to December 2015, a total of 204 patients were recruited. The LOS and hospital costs in the sham feeding group were reduced, although mortality was equivalent between groups. The return of gastrointestinal function occurred earlier in the sham feeding group, with no complications related to gum chewing. Conclusions Sham feeding with chewing gum is safe and efficacious in the early stage of AP. PMID:28154369

  12. Thermodynamics, morphology, and kinetics of early- stage self-assembly of pi-conjugated oligopeptides

    NASA Astrophysics Data System (ADS)

    Thurston, Bryce; Tovar, John; Ferguson, Andrew

    Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate self-assembly. At low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ~ - 25kB T . Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini. We model simulations of hundereds of monomers as a continuous-time Markov process. We infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates. Supported by U.S. Department of Energy, Office of Science, Basic Energy Sciences, Award DE-SC0004857. Molecular simulations partially conducted on University of Illinois Computational Science and Engineering Program parallel computing resources.

  13. Brain Event-Related Potentials: Diagnosing Early-Stage Alzheimer’s Disease

    PubMed Central

    Chapman, Robert M.; Nowlis, Geoffrey H.; McCrary, John W.; Chapman, John A.; Sandoval, Tiffany C.; Guillily, Maria D.; Gardner, Margaret N.; Reilly, Lindsey A.

    2009-01-01

    A pattern of components from brain Event-Related Potentials (ERP) (cognitive non-invasive electrical brain measures) performed well in separating early-stage Alzheimer’s disease (AD) subjects from normal-aging control subjects and shows promise for developing a clinical diagnostic for Probable AD. A Number-Letter task elicited brain activity related to cognitive processes. In response to the task stimuli, brain activity was recorded as ERPs, whose components were measured by Principal Components Analysis (PCA). The ERP component scores to relevant and irrelevant stimuli were used in Discriminant Analyses to develop functions that successfully classified individuals as belonging to an early-stage Alzheimer’s disease group or a like-aged Control group, with probabilities of an individual belonging to each group. Applying the discriminant function to the developmental half of the data showed 92% of the subjects were correctly classified into either the AD group or the Control group with a sensitivity of 1.00. The two crossvalidation results were good with sensitivities of 0.83 and classification accuracies of 0.75–0.79. P3 and CNV components, as well as other, earlier ERP components, e.g. C145 and the memory “Storage” component, were useful in the discriminant functions. PMID:16430992

  14. A decision-analytic model for early stage breast cancer: lumpectomy vs mastectomy.

    PubMed

    Büyükdamgaci-Alogan, G; Elele, T; Hayran, M; Erman, M; Kiliçkap, S

    2008-01-01

    The purpose was to construct a decision model that incorporated patient preferences over differing health state prospects and to analyze the decision context of early stage breast cancer patients in relation to two main surgical treatment options. A Markov chain was constructed to project the clinical history of breast carcinoma following surgery. A Multi Attribute Utility Model was developed for outcome evaluation. Transition probabilities were obtained by using subjective probability assessment. This study was performed on the sample population of female university students and utilities were elicited from these healthy volunteers. The results were validated by using Standard Gamble technique. Finally, Monte Carlo Simulation was utilized in Treeage-Pro 2006-Suit software program in order to calculate expected utility generated by each treatment option. The results showed that, if the subject had mastectomy, mean value for the quality adjusted life years gained was 6.42; on the other hand, if the preference was lumpectomy, it was 7.00 out of a possible 10 years. Sensitivity analysis on transition probabilities to local recurrence and salvaged states was performed and two threshold values were observed. Additionally, sensitivity analysis on utilities showed that the model was more sensitive to no evidence of disease state; however, was not sensitive to utilities of local recurrence and salvaged states. The decision model was developed with reasonable success for early stage breast cancer patients, and tested by using general public data. The results obtained from these data showed that lumpectomy was more favourable for these participants.

  15. Effects of marine toxins on the reproduction and early stages development of aquatic organisms.

    PubMed

    Vasconcelos, Vítor; Azevedo, Joana; Silva, Marisa; Ramos, Vítor

    2010-01-19

    Marine organisms, and specially phytoplankton species, are able to produce a diverse array of toxic compounds that are not yet fully understood in terms of their main targets and biological function. Toxins such as saxitoxins, tetrodotoxin, palytoxin, nodularin, okadaic acid, domoic acid, may be produced in large amounts by dinoflagellates, cyanobacteria, bacteria and diatoms and accumulate in vectors that transfer the toxin along food chains. These may affect top predator organisms, including human populations, leading in some cases to death. Nevertheless, these toxins may also affect the reproduction of aquatic organisms that may be in contact with the toxins, either by decreasing the amount or quality of gametes or by affecting embryonic development. Adults of some species may be insensitive to toxins but early stages are more prone to intoxication because they lack effective enzymatic systems to detoxify the toxins and are more exposed to the toxins due to a higher metabolic growth rate. In this paper we review the current knowledge on the effects of some of the most common marine toxins on the reproduction and development of early stages of some organisms.

  16. Properties of large scale plasma flow during the early stage of the plasmaspheric refilling

    NASA Technical Reports Server (NTRS)

    Singh, Nagendra; Craven, P.; Torr, D. G.; Richards, P. G.

    1990-01-01

    The objective is to better characterize the macroscopic properties of the interhemisphere plasma flow by solving a more complete set of hydrodynamic equations than that solved previously. Specifically, the ion continuity, momentum and energy equations were solved for the plasma flow along the closed magnetic field lines. During the initial stage of the supersonic outflow in the equatorial region, the ions cool substantially. Using the hydrodynamic model for the large-scale plasma flow, the dynamics of shocks was examined which form in the geomagnetic flux tubes during the early stages of refilling. These shocks are more like those forming in neutral gases than the electrostatic shocks driven by microinstabilities involving ion-ion interaction. Therefore, the shocks seen in the hydrodynamic model are termed as hydrodynamic shocks. Such shocks are generally unsteady and therefore the usual shock jump conditions given by Rankine-Hugoniot relations are not strictly applicable to them. The density, flow velocity and temperature structures associated with the shocks are examined for both asymmetrical and symmetrical flows. In the asymmetrical flow the outflow from one of two conjugate ionospheres is dominant. On the other hand, in the symmetrical case outflows from the two ionospheric sources are identical. Both cases are treated by a two-stream model. In the late type of flow, the early-time refilling shows a relaxation type of oscillation, which is driven by the large-scale interactions between the two identical streams. After this early stage, the resulting temperature structure shows some interesting features. In the equatorial region the streams are isothermal, but in the off-equatorial regions the streams have quite different temperatures, and also densities and flow velocities. The dense and slow stream is found to be warmer than the low-density fast stream. In the late stage of refilling, the temperature is found to steadily increase from the conjugate

  17. Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage MutantK-ras Lung Cancer

    DTIC Science & Technology

    2015-10-01

    would expect the results that we have seen. However, according to the cancer stem cell theory (5), transient amplifying cells have limited capacity...1 AWARD NUMBER: W81XWH-14-1-0338 TITLE: Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage Mutant K-ras Lung Cancer...COVERED 15 Sep 2014 - 14 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage

  18. Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

    PubMed

    Kaiserova, Michaela; Prikrylova Vranova, Hana; Galuszka, Jan; Stejskal, David; Mensikova, Katerina; Zapletalova, Jana; Mares, Jan; Kanovsky, Petr

    2015-10-01

    An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD.

  19. Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease

    PubMed Central

    Lebherz-Eichinger, Diana; Tudor, Bianca; Ankersmit, Hendrik J.; Reiter, Thomas; Haas, Martin; Roth-Walter, Franziska; Krenn, Claus G.; Roth, Georg A.

    2015-01-01

    Chronic kidney disease (CKD) is associated with high morbidity and mortality. In many patients CKD is diagnosed late during disease progression. Therefore, the implementation of potential biomarkers may facilitate the early identification of individuals at risk. Trefoil factor family (TFF) peptides promote restitution processes of mucous epithelia and are abundant in the urinary tract. We therefore sought to investigate the TFF peptide levels in patients suffering from CKD and their potential as biomarkers for CKD. We analysed TFF1 and TFF3 in serum and urine of 115 patients with CKD stages 1–5 without dialysis by ELISA. 20 healthy volunteers served as controls. Our results showed, that urinary TFF1 levels were significantly increased with the onset of CKD in stages 1–4 as compared to controls and declined during disease progression (p = 0.003, < 0.001, 0.005, and 0.007. median concentrations: 3.5 pg/mL in controls vs 165.2, 61.1, 17.2, and 15.8 pg/mL in CKD 1–4). TFF1 and TFF3 serum levels were significantly elevated in stages 3–5 as compared to controls (TFF1: p < 0.01; median concentrations: 12.1, 39.7, and 34.5 pg/mL in CKD 3–5. TFF3: p < 0.001; median concentrations: 7.1 ng/mL in controls vs 26.1, 52.8, and 78.8 ng/mL in CKD 3–5). TFF3 excretion was increased in stages 4 and 5 (p < 0.001; median urinary levels: 65.2 ng/mL in controls vs 231.5 and 382.6 ng/mL in CKD 4/5; fractional TFF3 excretion: 6.4 in controls vs 19.6 and 44.1 in CKD 4/5). ROC curve analyses showed, that monitoring TFF peptide levels can predict various CKD stages (AUC urinary/serum TFF > 0.8). In conclusion our results show increased levels of TFF1 and TFF3 in CKD patients with a pronounced elevation of urinary TFF1 in lower CKD stages. Furthermore, TFF1 and TFF3 seems to be differently regulated and show potential to predict various CKD stages, as shown by ROC curve analysis. PMID:26390128

  20. Application of Carnegie stages of development to unify human and baboon ultrasound findings early in pregnancy.

    PubMed

    Santolaya-Forgas, Joaquin; De Leon-Luis, Juan; Friel, Lara A; Wolf, Roman

    2007-09-01

    The objective of this study was to determine if very early ultrasonographic measurements obtained from human and baboon are comparable. For this purpose, the gestational, amniotic and yolk sacs, embryonic crown rump length (CRL) and heart rate were measured ultrasonographically between 35 and 47 days from the mean day of a three-day mating period in baboons (n=18) and between 42 to 58 days from fertilization as calculated from the CRL measurements in human pregnancies (n=82). Ultrasonographic measurements from both species were then plotted in the same graph using Carnegie stages of embryonic development as the independent variable to allow for visual comparisons. Mean gestational age at ultrasonographic studies was significantly different for humans and baboons (50.4 vs. 41 days, respectively; p>0.01). Significant correlations (p>0.01) were noted between ultrasonographic measurements and Carnegie stages of development in both humans and baboons. Only the gestational and the yolk sacs were significantly smaller in baboons than in humans (p>0.05). The findings that embryonic CRL, extra-embryonic space and heart rate are very similar between the 17th and 23rd Carnegie developmental stages make the baboon a promising surrogate of human pregnancy for investigations using celocentesis.

  1. Identification of genes involved in rice seed priming in the early imbibition stage.

    PubMed

    Cheng, J; Wang, L; Zeng, P; He, Y; Zhou, R; Zhang, H; Wang, Z

    2017-01-01

    Phase II of seed imbibition is a critical process during seed priming. To identify genes involved in rice seed priming, the altered proteins between the dry and imbibed (24 h) seeds were compared using a two-dimensional gel electrophoresis system in this study. Ten significantly changed proteins (fold change ≥ twofold; P < 0.01) were successfully identified, which could be categorised as carbohydrate and protein biosynthesis and metabolism-related, signalling-related, storage and stress-related proteins. A meta-analysis indicated that the highest expression of the identified genes was at the milk and dough stages and in the endosperm tissue. Quantitative real-time PCR analysis showed that there was significant variation in gene expression (except FAD-dependent oxidoreductase) in embryos during seed priming (0-48 h). The expression of genes associated with stress appeared at the early imbibition stage, while those associated with carbohydrate metabolism, protein synthesis and signalling increased at the late imbibition stage. Three identified proteins (glucose-1-phosphate adenylyltransferase large subunit, aminotransferase and prolamin precursor) had similar transcript and protein expression patterns in embryos. Based on phenotype and gene expression, the optimal stop time for seed priming is 24 h, when these three genes have relatively low expression, followed by significant induction during imbibition in embryos. These three genes are ideal candidate biomarkers for rice seed priming.

  2. Early-Stage Young Breast Cancer Patients: Impact of Local Treatment on Survival

    SciTech Connect

    Bantema-Joppe, Enja J.; Munck, Linda de; Willemse, Pax H.B.; Langendijk, Johannes A.; Siesling, Sabine; Maduro, John H.

    2011-11-15

    Purpose: In young women, breast-conserving therapy (BCT), i.e., lumpectomy followed by radiotherapy, has been associated with an increased risk of local recurrence. Still, there is insufficient evidence that BCT impairs survival. The aim of our study was to compare the effect of BCT with mastectomy on overall survival (OS) in young women with early-stage breast cancer. Methods and Materials: From two Dutch regional population-based cancer registries (covering 6.2 million inhabitants) 1,453 women <40 years with pathologically T1N0-1M0 breast cancer were selected. Cox regression survival analysis was used to study the effect of local treatment (BCT vs. mastectomy) stratified for nodal stage on survival and corrected for tumor size, age, period of diagnosis, and use of adjuvant systemic therapy. Results: With a median follow-up of 9.6 years, 10-year OS was 83% after BCT and 78% after mastectomy, respectively (unadjusted hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.09-1.72). In N0-patients, 10-year OS was 84% after BCT and 81% after mastectomy and local treatment was not associated with differences in OS (HR 1.19; 95% CI, 0.89-1.58; p = 0.25). Within the N1-patient group, OS was better after BCT compared with mastectomy, 79% vs. 71% at 10 years (HR 1.91; 95% CI, 1.28-2.84; p = 0.001) and in patients treated with adjuvant hormonal therapy (HR 0.34; 95% CI, 0.18-0.66; p = 0.001). Conclusions: In this large population-based cohort of early-stage young breast cancer patients, 10-year OS was not impaired after BCT compared with mastectomy. Patients with 1 to 3 positive lymph nodes had better prognosis after BCT than after mastectomy.

  3. Developmental and physiological challenges of octopus (Octopus vulgaris) early life stages under ocean warming.

    PubMed

    Repolho, Tiago; Baptista, Miguel; Pimentel, Marta S; Dionísio, Gisela; Trübenbach, Katja; Lopes, Vanessa M; Lopes, Ana Rita; Calado, Ricardo; Diniz, Mário; Rosa, Rui

    2014-01-01

    The ability to understand and predict the effects of ocean warming (under realistic scenarios) on marine biota is of paramount importance, especially at the most vulnerable early life stages. Here we investigated the impact of predicted environmental warming (+3 °C) on the development, metabolism, heat shock response and antioxidant defense mechanisms of the early stages of the common octopus, Octopus vulgaris. As expected, warming shortened embryonic developmental time by 13 days, from 38 days at 18 °C to 25 days at 21 °C. Concomitantly, survival decreased significantly (~29.9 %). Size at hatching varied inversely with temperature, and the percentage of smaller premature paralarvae increased drastically, from 0 % at 18 °C to 17.8 % at 21 °C. The metabolic costs of the transition from an encapsulated embryo to a free planktonic form increased significantly with warming, and HSP70 concentrations and glutathione S-transferase activity levels were significantly magnified from late embryonic to paralarval stages. Yet, despite the presence of effective antioxidant defense mechanisms, ocean warming led to an augmentation of malondialdehyde levels (an indicative of enhanced ROS action), a process considered to be one of the most frequent cellular injury mechanisms. Thus, the present study provides clues about how the magnitude and rate of ocean warming will challenge the buffering capacities of octopus embryos and hatchlings' physiology. The prediction and understanding of the biochemical and physiological responses to warmer temperatures (under realistic scenarios) is crucial for the management of highly commercial and ecologically important species, such as O. vulgaris.

  4. Analysis of cerebro-spinal fluid protein composition in early developmental stages in chick embryos.

    PubMed

    Gato, A; Martín, P; Alonso, M I; Martín, C; Pulgar, M A; Moro, J A

    2004-04-01

    Foetal cerebro-spinal fluid (CSF) has a very high protein concentration when compared to adult CSF, and in many species five major protein fractions have been described. However, the protein concentration and composition in CSF during early developmental stages remains largely unknown. Our results show that in the earliest stages (18 to 30 H.H.) of chick development there is a progressive increase in CSF protein concentration until foetal values are attained. In addition, by performing electrophoretic separation and high-sensitivity silver staining, we were able to identify a total of 21 different protein fractions in the chick embryo CSF. In accordance with the developmental pattern of their concentration, these can be classified as follows: A: high-concentration fractions which corresponded with the ones described in foetal CSF by other authors; B: low-concentration fractions which remained stable throughout the period studied; C: low-concentration fractions which show changes during this period. The evolution and molecular weight of the latter group suggest the possibility of an important biological role. Our data demonstrate that all the CSF protein fractions are present in embryonic serum; this could mean that the specific transport mechanisms in neuroepithelial cells described in the foetal period evolve in very early stages of development. In conclusion, this paper offers an accurate study of the protein composition of chick embryonic CSF, which will help the understanding of the influences on neuroepithelial stem cells during development and, as a result, the appropriate conditions for the in vitro study of embryonic/foetal nervous tissue cells.

  5. Tangential Radiotherapy Without Axillary Surgery in Early-Stage Breast Cancer: Results of a Prospective Trial

    SciTech Connect

    Wong, Julia S.; Winer, Eric P.

    2008-11-01

    Purpose: To determine the risk of regional-nodal recurrence in patients with early-stage, invasive breast cancer, with clinically negative axillary nodes, who were treated with breast-conserving surgery, 'high tangential' breast radiotherapy, and hormonal therapy, without axillary surgery or the use of a separate nodal radiation field. Methods and Materials: Between September 1998 and November 2003, 74 patients who were {>=}55 years of age with Stage I-II clinically node-negative, hormone-receptor-positive breast cancer underwent tumor excision to negative margins without axillary surgery as a part of a multi-institutional prospective study. Postoperatively, all underwent high-tangential, whole-breast radiotherapy with a boost to the tumor bed, followed by 5 years of hormonal therapy. Results: For the 74 patients enrolled, the median age was 74.5 years, and the median pathologic tumor size was 1.2 cm. Lymphatic vessel invasion was present in 5 patients (7%). At a median follow-up of 52 months, no regional-nodal failures or ipsilateral breast recurrences had been identified (95% confidence interval, 0-4%). Eight patients died, one of metastatic disease and seven of other causes. Conclusion: In this select group of mainly older patients with early-stage hormone-responsive breast cancer and clinically negative axillary nodes, treatment with high-tangential breast radiotherapy and hormonal therapy, without axillary surgery, yielded a low regional recurrence rate. Such patients might be spared more extensive axillary treatment (axillary surgery, including sentinel node biopsy, or a separate nodal radiation field), with its associated time, expense, and morbidity.

  6. A Candida albicans early stage biofilm detachment event in rich medium

    PubMed Central

    2009-01-01

    Background Dispersal from Candida albicans biofilms that colonize catheters is implicated as a primary factor in the link between contaminated catheters and life threatening blood stream infections (BSI). Appropriate in vitro C. albicans biofilm models are needed to probe factors that induce detachment events. Results Using a flow through system to culture C. albicans biofilms we characterized a detachment process which culminates in dissociation of an entire early stage biofilm from a silicone elastomer surface. We analyzed the transcriptome response at time points that bracketed an abrupt transition in which a strong adhesive association with the surface is weakened in the initial stages of the process, and also compared batch and biofilm cultures at relevant time points. K means analysis of the time course array data revealed categories of genes with similar patterns of expression that were associated with adhesion, biofilm formation and glycoprotein biosynthesis. Compared to batch cultures the biofilm showed a pattern of expression of metabolic genes that was similar to the C. albicans response to hypoxia. However, the loss of strong adhesion was not obviously influenced by either the availability of oxygen in the medium or at the silicone elastomer surface. The detachment phenotype of mutant strains in which selected genes were either deleted or overexpressed was characterized. The microarray data indicated that changes associated with the detachment process were complex and, consistent with this assessment, we were unable to demonstrate that transcriptional regulation of any single gene was essential for loss of the strong adhesive association. Conclusion The massive dispersal of the early stage biofilm from a biomaterial surface that we observed is not orchestrated at the level of transcriptional regulation in an obvious manner, or is only regulated at this level by a small subpopulation of cells that mediate adhesion to the surface. PMID:19187560

  7. The incidence of bone metastasis after early-stage breast cancer in Canada.

    PubMed

    Liede, Alexander; Jerzak, Katarzyna J; Hernandez, Rohini K; Wade, Sally W; Sun, Ping; Narod, Steven A

    2016-04-01

    Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan-Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US.

  8. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia.

  9. Development of Valpha4+ NK T cells in the early stages of embryogenesis.

    PubMed Central

    Makino, Y; Kanno, R; Koseki, H; Taniguchi, M

    1996-01-01

    The majority of T lymphocytes start to develop at around day 15 of gestation (d15)-d17 in the thymus and comprise the peripheral repertoire characterized by the expression of polymorphic T-cell antigen receptors (TCRs). Contrary to these conventional T cells, a subset of T cells, called natural killer (NK) T cells (most of them expressing an invariant TCR encoded by the Valpha14Jalpha281 gene with a 1-nt N-region), preferentially differentiates extrathymically and dominates the peripheral T-cell population at a high frequency (5% in splenic T cells and 40% in bone marrow T cells). Here, we investigated the development of NK T cells and found that the invariant Valpha14+ TCR transcripts and the circular DNA created by Valpha14 and Jalpha281 gene rearrangements can be detected in the embryo body at d9.5 of gestation and in the yolk sac and the fetal liver at d11.5-d13.5 of gestation, but not in the thymus, whereas T cells with Valpha1+ TCR expression, a major population in the thymus, were not observed at these early stages of gestation. Fluorescence-activated cell sorter analysis also demonstrated that there exist CD3+ alpha beta+ T cells, almost all of which are Valpha14/Vbeta8+ NK+ T cells, during early embryogenesis. To our knowledge, this demonstrates for the first time that a T lymphocyte subset develops in extrathymic tissues during the early stages of embryogenesis. Images Fig. 1 Fig. 4 PMID:8692847

  10. Physiological and morphological changes during early and later stages of fruit growth in Capsicum annuum.

    PubMed

    Tiwari, Aparna; Vivian-Smith, Adam; Ljung, Karin; Offringa, Remko; Heuvelink, Ep

    2013-03-01

    Fruit-set involves a series of physiological and morphological changes that are well described for tomato and Arabidopsis, but largely unknown for sweet pepper (Capsicum annuum). The aim of this paper is to investigate whether mechanisms of fruit-set observed in Arabidopsis and tomato are also applicable to C. annuum. To do this, we accurately timed the physiological and morphological changes in a post-pollinated and un-pollinated ovary. A vascular connection between ovule and replum was observed in fertilized ovaries that undergo fruit development, and this connection was absent in unfertilized ovaries that abort. This indicates that vascular connection between ovule and replum is an early indicator for successful fruit development after pollination and fertilization. Evaluation of histological changes in the carpel of a fertilized and unfertilized ovary indicated that increase in cell number and cell diameter both contribute to early fruit growth. Cell division contributes more during early fruit growth while cell expansion contributes more at later stages of fruit growth in C. annuum. The simultaneous occurrence of a peak in auxin concentration and a strong increase in cell diameter in the carpel of seeded fruits suggest that indole-3-acetic acid stimulates a major increase in cell diameter at later stages of fruit growth. The series of physiological and morphological events observed during fruit-set in C. annuum are similar to what has been reported for tomato and Arabidopsis. This indicates that tomato and Arabidopsis are suitable model plants to understand details of fruit-set mechanisms in C. annuum.

  11. Annual surveillance mammography after early-stage breast cancer and breast cancer mortality

    PubMed Central

    Paszat, L.F.; Sutradhar, R.; Gu, S.; Rakovitch, E.

    2016-01-01

    Background After treatment for early-stage breast cancer (bca), annual surveillance mammography (asm) is recommended based on the assumption that early detection of an invasive ipsilateral breast tumour recurrence or subsequent invasive contralateral primary bca reduces bca mortality. Methods We studied women with unilateral early-stage bca treated by breast-conserving surgery from 1994 to 1997 who subsequently developed an ipsilateral recurrence or contralateral primary more than 24 months after initial diagnosis, without prior regional or distant metastases. Annual surveillance mammography was defined as 2 episodes of bilateral mammography 11–18 months apart during the 2 years preceding the ipsilateral recurrence or contralateral primary. The association between asm and bca death was evaluated using a Cox proportional hazards model. Results We identified 669 women who experienced invasive ipsilateral recurrence (n = 455) or a contralateral primary (n = 214) at a median interval of 53 months [interquartile range (iqr): 37–72 months] after initial diagnosis, 64.7% of whom had received asm during the preceding 2 years. The median interval between the 2 bilateral mammograms was 12.3 months (iqr: 11.9–13.0 months), and the median interval between the 2nd mammogram and histopathologic confirmation of ipsilateral recurrence or contralateral primary was 1.5 months (iqr: 0.8–3.9 months). Median followup after ipsilateral recurrence or contralateral primary was 7.76 years (iqr: 3.68–9.81 years). The adjusted hazard ratio for bca death associated with asm was 0.86 (95% confidence limits: 0.63, 1.16). Conclusions Annual surveillance mammography was associated with a modestly lowered hazard ratio for bca death. PMID:28050142

  12. [Prenatal cerebrovascular accidents diagnosed in the early infant stage: a series of 10 patients].

    PubMed

    Pina-Jover, María; Martinez-Del Villar, María; Lillo-Laguna, Lucía; Jadraque-Rodriguez, Rocío; Martinez-Pastor, Pedro; Jover-Cerda, Jenaro; Gomez-Gosalvez, Francisco

    2013-07-01

    INTRODUCTION. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. PATIENTS AND METHODS. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. RESULTS. None of the 10 patients studied presented any relevant events in the mothers' medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. CONCLUSIONS. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible.

  13. Adoption of Intensity Modulated Radiation Therapy For Early-Stage Breast Cancer From 2004 Through 2011

    SciTech Connect

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Smith, Benjamin D.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2015-02-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials: We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results: We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions: The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.

  14. Oxidative reactions during early stages of beer brewing studied by electron spin resonance and spin trapping.

    PubMed

    Frederiksen, Anne M; Festersen, Rikke M; Andersen, Mogens L

    2008-09-24

    An electron spin resonance (ESR)-based method was used for evaluating the levels of radical formation during mashing and in sweet wort. The method included the addition of 5% (v/v) ethanol together with the spin trap alpha-4-pyridyl(1-oxide)- N- tert-butylnitrone (POBN) to wort, followed by monitoring the rate of formation of POBN spin adducts during aerobic heating of the wort. The presence of ethanol makes the spin trapping method more selective and sensitive for the detection of highly reactive radicals such as hydroxyl and alkoxyl radicals. Samples of wort that were collected during the early stages of the mashing process gave higher rates of spin adduct formation than wort samples collected during the later stages. The lower oxidative stability of the early wort samples was confirmed by measuring the rate of oxygen consumption during heating of the wort. The addition of Fe(II) to the wort samples increased the rate of spin adduct formation, whereas the addition of Fe(II) during the mashing had no effect on the oxidative stability of the wort samples. Analysis of the iron content in the sweet wort samples demonstrated that iron added during the mashing had no effect on the iron level in the wort. The moderate temperatures during the early steps of mashing allow the endogenous malt enzymes to be active. The potential antioxidative effects of different redox-active enzymes during mashing were tested by measuring the rate of spin adduct formation in samples of wort. Surprisingly, a high catalase dosage caused a significant, 20% reduction of the initial rate of radical formation, whereas superoxide dismutase had no effect on the oxidation rates. This suggests that hydrogen peroxide and superoxide are not the only intermediates that play a role in the oxidative reactions occurring during aerobic oxidation of sweet wort.

  15. Potential diagnostic role of diffusion tensor imaging in early-stage osteonecrosis of the femoral head

    PubMed Central

    Min, Hongwei; Xu, Feng; Gu, Rui; Han, Xinzuo; Wang, Anqing; Liu, Kemin

    2016-01-01

    The present study aimed to explore the potential diagnostic role of diffusion tensor magnetic resonance imaging (DTI) in the early stage of modified corticosteroid-induced osteonecrosis of the femoral head (ONFH). A total of 20 beagles were randomly classified (1:1) into either an experimental group (LM), which were intramuscularly injected with lipopolysaccharide (LPS) and methylprednisolone (MPS) on three consecutive days, or control (CON) group, which were injected with saline. Magnetic resonance imaging (MRI) and DTI were performed at pre-induction and 8 and 12 weeks post-induction. Apparent diffusion coefficient (ADC) values in the range of interest in the femoral head were quantified using DTI. Proximal femora were examined for ONFH at 8 and 12 weeks. The results demonstrated that ONFH developed in four beagles at 8 weeks and in six beagles at 12 weeks, whereas no ONFH was detected in the CON group. No abnormalities were detected by MRI and DTI, and no mortality occurred. In beagles with ONFH in the LM group, the ADC values were 4.7±0.2×10−4 and 4.8±0.3×10−4 mm2/sec at 8 and 12 weeks, respectively, which were significantly increased compared with the CON group (2.5±0.3×10−4 and 2.4±0.3×10−4 mm2, respectively) and the LM group without ONFH (2.6±0.4×10−4 and 2.4±0.3×10−4 mm2, respectively) (P<0.05). The results of the present study indicated that intramuscular injection of LPS and MPS may lead to early-stage ONFH in beagles. As such, the detection of locally elevated ADC values in the femoral head may aid in the early diagnosis of ONFH. PMID:27882161

  16. The role of norepinephrine and insulin resistance in an early stage of hypertension.

    PubMed

    Penesova, Adela; Radikova, Zofia; Cizmarova, Eva; Kvetnanský, Richard; Blazicek, Pavel; Vlcek, Miroslav; Koska, Juraj; Vigas, Milan

    2008-12-01

    The interrelationship between activity of sympathetic nervous system and metabolic risk factors in youth with hypertension (HT) has been poorly studied. The aim of our present study was to assess the interrelationship between metabolic risk factors, such as insulin resistance, concentration of plasminogen activator inhibitor (PAI)-1, and catecholamines in an early stage of HT onset. An oral glucose tolerance test was performed in 17 young males with early-diagnosed nontreated HT grade 1 and 16 gender-, age-, and BMI-matched normotensive controls. Concentrations of glucose, insulin, epinephrine, norepinephrine, PAI-1, and plasma renin activity (PRA) were determined in venous plasma. Insulin sensitivity indices (ISIs) proposed by Cederholm, Matsuda, and Gutt were calculated. HT had higher baseline levels of norepinephrine, insulin (P= 0.02), and PAI-1 (P= 0.04). ISIs were lower in HT subjects (P < 0.001). Baseline concentrations of epinephrine were negatively associated with HDL cholesterol (r=-0.415, P= 0.02), ISI Matsuda (r=-0.361, P= 0.04), ISI Cederholm (r=-0.354, P= 0.04), and ISI Gutt (r=-0.429, P= 0.01), and positively with PRA (r= 0.609, P < 0.0001). Positive association was found between baseline concentrations of norepinephrine and PAI-1 (r= 0.418, P= 0.02). The sympathetic overactivity, which occurs in the early stage of HT may contribute to reduced insulin sensitivity even in young patients and intensify the undesirable development of metabolic cardiovascular risk factors and progress of the disease.

  17. Growth and physiological responses of Chinese cabbage cv. 'Chungwang' to different irradiances during early-to-middle growth stages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Changes of the growth and morphology of Chinese cabbage cv. ‘Chungwang’ in response to five different irradiance treatments were investigated during the early and middle stages of growth. Seedlings were transplanted to 15 liter pots at the fourth leaf stage and plants were grown in controlled enviro...

  18. Towards a formal and scalable approach for quantifying software reliability at early development stages

    NASA Astrophysics Data System (ADS)

    Kong, Wende

    2009-12-01

    Problems which originate in early development stages can have a lasting influence on the reliability, safety, and cost of a software system. The requirements document, which is usually available at the requirements analysis stage, must be correct, unambiguous, and complete if the rest of the development effort is to succeed. The ability to identify faults in requirements and predict the reliability of a software system early in its development can help organizations make informative decisions about corrective actions and improve the system's quality in a cost-effective manner. A review of the literature reveals that existing approaches are unsuited to provide trustworthy reliability prediction either due to the ignorance of the requirements documents, or because of the informal and fairly sketchy way in detecting faults in requirements. This study explores the use of a preselected software reliability measurement for early software faults detection and reliability prediction. This measurement, originally a black-box testing technique, was broadly recognized for its ability to detect incomplete and ambiguous requirements, although no information was found in the literature about how to take advantage of its power. This study mathematically formalized the measurement to enhance its rigidity, repeatability and scalability and further extended it as an effective requirements faults detection technique. An automation-oriented algorithm was developed for quantifying the impact of the detected requirements faults on software reliability. The feasibility and scalability of the proposed approach for early faults detection and reliability prediction were examined using two real applications. The results clearly confirmed its feasibility and usefulness, particularly when no failure data is available and other methods are not applicable. The scalability barriers were also spotted in the approach. An empirical study was thus conducted to gain insight into the nature of the

  19. Left atrial enlargement in the early stage of hypertensive heart disease: a common but ignored condition.

    PubMed

    Su, Guanhua; Cao, Heng; Xu, Sudan; Lu, Yongxin; Shuai, Xinxin; Sun, Yufei; Liao, Yuhua; Li, Jingdong

    2014-03-01

    How to identify the early signs of hypertensive heart disease is the key to block or reverse the process of heart failure. The aim of this study was to evaluate the predictive value of left atrial (LA) enlargement in the early stage of hypertensive heart disease and to explore the correlations between LA enlargement and heart failure with normal ejection fraction (HFnEF), as well as the metabolic syndrome (MetS). Baseline clinical characteristics, biochemical indices, electrocardiographic and echocardiographic data were collected from 341 consecutive patients with essential hypertension. Among those patients, LA enlargement was more frequently presented than LV enlargement (57.2% vs 17.9%). Compared with patients without HFnEF, the prevalence of LA enlargement was higher in patients with HFnEF (82.9% vs 49.0%, P<.0001). From grade 2 to grade 3 hypertension, LA size was significantly larger in patients with MetS (P<.01) than those without. Multivariate linear regression analyses showed that age, body mass index, waist circumference, triglyceride level, and left ventricular diameter were independent predictors of LA enlargement. The simple measurement for identification of LA enlargement potentially allows early recognition of those patients at risk for heart failure, particularly among patients with MetS.

  20. Virion-incorporated alpha-enolase suppresses the early stage of HIV-1 reverse transcription.

    PubMed

    Kishimoto, Naoki; Iga, Nozomi; Yamamoto, Kengo; Takamune, Nobutoki; Misumi, Shogo

    2017-03-04

    Human immunodeficiency virus type-1 (HIV-1) particles contain not only viral-encoded but also host-encoded proteins. Interestingly, several studies showed that host proteins play a critical role in viral infectivity, replication and/or immunoreactivity in the next target cells. Here, we show that alpha-enolase (ENO1) is incorporated into HIV-1 virions and the virion-incorporated ENO1 prevents the early stage of HIV-1 reverse transcription. We found that viral particles contain two isoforms of ENO1 with different isoelectric points by two-dimensional electrophoresis. Suppression of ENO1 expression by RNA interference in the HIV-1 producer cells decreased ENO1 incorporation into virions without altering the packaging of viral structural proteins and viral production but increased viral infectivity. Although the low-level-ENO1-packaging virus maintained comparable levels of reverse transcriptase activity, viral genomic RNA and tRNA(Lys3) packaging to the control virus, its levels of early cDNA products of reverse transcription were higher than those of the control virus. In contrast, the high-level-ENO1-packaging virus, which was produced from ENO1-overexpressing cells, showed decreased infectivity and the levels of early cDNA products. Taken together, these findings reveal a novel function of ENO1 as a negative regulation factor targeting HIV-1 reverse transcription.

  1. Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma

    PubMed Central

    Chávez-López, María de Guadalupe; Zúñiga-García, Violeta; Pérez-Carreón, Julio Isael; Avalos-Fuentes, Arturo; Escobar, Yesenia; Camacho, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide. HCC is usually asymptomatic at potential curative stages, and it has very poor prognosis if detected later. Thus, the identification of early biomarkers and novel therapies is essential to improve HCC patient survival. Ion channels have been proposed as potential tumor markers and therapeutic targets for several cancers including HCC. Especially, the ether à-go-go-1 (Eag1) voltage-gated potassium channel has been suggested as an early marker for HCC. Eag1 is overexpressed during HCC development from the cirrhotic and the preneoplastic lesions preceding HCC in a rat model. The channel is also overexpressed in human HCC. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including Eag1. Actually, in vivo studies have shown that astemizole may have clinical utility for HCC prevention and treatment. Here, we will review first some general aspects of HCC including the current biomarkers and therapies, and then we will focus on Eag1 channels as promising tools in the early diagnosis of HCC. PMID:27703327

  2. Quantifying the early stages of remyelination following cuprizone-induced demyelination.

    PubMed

    Stidworthy, Mark F; Genoud, Stephane; Suter, Ueli; Mantei, Ned; Franklin, Robin J M

    2003-07-01

    The demyelinating toxin cuprizone is used increasingly in mouse studies of central nervous system remyelination. The value of this model for such studies depends on an accurate description of its quantifiable features. We therefore investigated histology and ultrastructure during the early oligodendrocyte differentiation phase of remyelination in mice given cuprizone and allowed to recover for 2 weeks. Limiting the dose of cuprizone to 0.2% overcame significant mouse morbidity and weight loss seen with a 0.4% dose, but the distribution of cuprizone-induced demyelination was anatomically variable. The caudal corpus callosum and dorsal hippocampal commissure mostly demyelinated at this dose, but the rostral corpus callosum and rostral cerebellar peduncles did not. This variable response, together with small axon diameters and hence thin myelin sheaths, hindered analysis of the progress of early remyelination. The proportion of myelinated and unmyelinated axons in defined regions followed expected trends, but there was pronounced variation between animals. Furthermore, group mean G ratios did not change as expected during the early stages of remyelination, and regression analysis revealed a complex relationship between axon diameter and myelin sheath thickness during this period. We also noted axonal pathology that persisted for at least 2 weeks after cuprizone withdrawal.

  3. Proteomic identification of abnormally expressed proteins in early-stage placenta derived from cloned cat embryos.

    PubMed

    Bang, Jae-Il; Lee, Hyo-Sang; Deb, Gautam Kumar; Ha, A-Na; Kwon, Young-Sang; Cho, Seong-Keun; Kim, Byeong-Woo; Cho, Kyu-Woan; Kong, Il-Keun

    2013-01-15

    It is unknown whether gene expression in cloned placenta during pre- and postimplantation is associated with early pregnancy failure in the cat. In this study, protein expression patterns were examined in early-stage (21-day-old) domestic cat placentas of fetuses derived from AI (CP; N = 4) and cloned embryo transfer (CEP; N = 2). Differentially expressed proteins were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight (TOF) mass spectrometry (MS). A total of 21 proteins were aberrantly expressed (P < 0.05) by >1.5-fold in CEP compared with CP. Compared with CP, 12 proteins were upregulated in CEP (peptidyl-prolyl cis-trans isomerase A, annexin A2, protein DJ-1, adenylate kinase isoenzyme 1, protein disulfide-isomerase A3, actin cytoplasmic 1, serum albumin, protein disulfide-isomerase A6, and triosephosphate isomerase), and nine proteins were downregulated (triosephosphate isomerase; heterogeneous nuclear ribonucleoprotein H; tropomyosin alpha-4; triosephosphate isomerase 1; 60 kDa heat shock protein, mitochondrial; serum albumin; calumenin; keratin type 1; and prohibitin). The identities of the differentially expressed proteins were validated by peptide mass fingerprinting using matrix-assisted laser desorption/ionization-TOF/TOF MS/MS. The abnormally expressed proteins identified in this study might be associated with impaired development and dysfunction of CEP during early pregnancy. Abnormal protein expression might also induce fetal loss and contribute to failure to maintain pregnancy to term.

  4. Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease

    SciTech Connect

    Lehericy, S.; Baulac, M.; Chiras, J.; Pierot, L.; Martin, N.; Pillon, B.; Deweer, B.; Dubois, B.; Marsault, C.

    1994-05-01

    To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status {ge} 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. For patients with a minimental status score of 21 or greater, atrophy was significant for the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease. 46 refs., 8 figs., 2 tabs.

  5. Acute CO2 tolerance during the early developmental stages of four marine teleosts.

    PubMed

    Kikkawa, T; Ishimatsu, A; Kita, J

    2003-12-01

    Ocean sequestration of CO2 is proposed as a possible measure to mitigate climate changes caused by increasing atmospheric concentrations of the gas, but its impact on the marine ecosystem is unknown. We investigated the acute lethal effect of CO2 during the early developmental stages of four marine teleosts: red sea bream (Pagrus major), Japanese whiting (Sillago japonica), Japanese flounder (Paralichthys olivaceus), and eastern little tuna (Euthynnus affinis). The percentages of larvae that hatched and survived were not affected by exposure to water with a PCO2 of 1.0 kPa (= 7.5 mmHg) within 24 h. Median lethal PCO2 values for a 360-min exposure were 1.4 kPa (cleavage), 5.1 kPa (embryo), 7.3 kPa (preflexion), 4.2 kPa (flexion), 4.6 kPa (postflexion), and 2.5 kPa (juvenile) for red sea bream; 2.4 kPa (cleavage), 4.9 kPa (embryo), 5.9 kPa (preflexion), 6.1 kPa (flexion), 4.1 kPa (postflexion), and 2.7 kPa (juvenile) for Japanese whiting; 2.8 kPa (cleavage) and > 7.0 kPa (young) for Japanese flounder; and 11.8 kPa (cleavage) for eastern little tuna. Red sea bream and Japanese whiting of all ontogenetic stages had similar susceptibilities to CO2: the most susceptible stages were cleavage and juvenile, whereas the most tolerant stages were preflexion and flexion.

  6. Ultrastructure of Fibre and Parenchyma Cell Walls During Early Stages of Culm Development in Dendrocalamus asper

    PubMed Central

    GRITSCH, CRISTINA SANCHIS; MURPHY, RICHARD J.

    2005-01-01

    • Background and Aims The anatomy of bamboo culms and the multilayered structure of fibre cell walls are known to be the main determinant factors for its physical and mechanical properties. Studies on the bamboo cell wall have focussed mainly on fully elongated and mature fibres. The main aim of this study was to describe the ultrastructure of primary and secondary cell walls in culm tissues of Dendrocalamus asper at different stages of development. • Methods The development of fibre and parenchyma tissues was classified into four stages based on light microscopy observations made in tissues from juvenile plants. The stages were used as a basis for transmission electron microscopy study on the ultrastructure of the cell wall during the process of primary and early secondary cell wall formation. Macerations and phloroglucinol–HCl staining were employed to investigate fibre cell elongation and fibre cell wall lignification, respectively. • Key Results The observations indicated that the primary wall is formed by the deposition of two distinct layers during the elongation of the internode and that secondary wall synthesis may begin before the complete cessation of internode and fibre elongation. Elongation was followed by a maturation phase characterized by the deposition of multiple secondary wall layers, which varied in number according to the cell type, location in the culm tissue and stage of shoot development. Lignification of fibre cell walls started at the period prior to the cessation of internode elongation. • Conclusions The structure of the primary cell wall was comprised of two layers. The fibre secondary cell wall began to be laid down while the cells were still undergoing some elongation, suggesting that it may act to cause the slow-down and eventual cessation of cell elongation. PMID:15665037

  7. NUCLEAR EGFR PROTEIN EXPRESSION PREDICTS POOR SURVIVAL IN EARLY STAGE NON-SMALL CELL LUNG CANCER

    PubMed Central

    Traynor, Anne M.; Weigel, Tracey L.; Oettel, Kurt R.; Yang, David T.; Zhang, Chong; Kim, KyungMann; Salgia, Ravi; Iida, Mari; Brand, Toni M.; Hoang, Tien; Campbell, Toby C.; Hernan, Hilary R.; Wheeler, Deric L.

    2013-01-01

    Introduction Nuclear EGFR (nEGFR) has been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus, and has predicted poor patient outcomes. We sought to determine if protein expression of nEGFR is prognostic in early stage non-small cell lung cancer (NSCLC). Methods Resected stage I and II NSCLC specimens were evaluated for nEGFR protein expression using immunohistochemistry (IHC). Cases with at least one replicate core containing ≥5% of tumor cells demonstrating strong dot-like nucleolar EGFR expression were scored as nEGFR positive. Results Twenty-three (26.1% of the population) of 88 resected specimens stained positively for nEGFR. Nuclear EGFR protein expression was associated with higher disease stage (45.5% of stage II vs. 14.5% of stage I; p=0.023), histology (41.7% in squamous cell carcinoma vs. 17.1% in adenocarcinoma; p=0.028), shorter progression-free survival (PFS) (median PFS 8.7 months [95% CI 5.1–10.7 mo] for nEGFR positive vs. 14.5 months [95% CI 9.5–17.4 mo] for nEGFR negative; hazard ratio (HR) of 1.89 [95% CI 1.15–3.10]; p=0.011), and shorter overall survival (OS) (median OS 14.1 months [95% CI 10.3–22.7 mo] for nEGFR positive vs. 23.4 months [95% CI 20.1–29.4 mo] for nEGFR negative; HR of 1.83 [95% CI 1.12–2.99]; p=0.014). Conclusions Expression of nEGFR protein was associated with higher stage and squamous cell histology, and predicted shorter PFS and OS, in this patient cohort. Nuclear EGFR serves as a useful independent prognostic variable and as a potential therapeutic target in NSCLC. PMID:23628526

  8. Efficacy of Intensity Modulated Radiation Therapy After Surgery in Early Stage of Esophageal Carcinoma;

    ClinicalTrials.gov

    2016-07-30

    Esophageal Neoplasm; Esophageal Cancer TNM Staging Primary Tumor (T) T2; Esophageal Cancer TNM Staging Primary Tumor (T) T3; Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0; Esophageal Cancer TNM Staging Distal Metastasis (M) M0

  9. In situ nanomechanical characterization of the early stages of swelling and degradation of a biodegradable polymer

    NASA Astrophysics Data System (ADS)

    Dumitru, A. C.; Espinosa, F. M.; Garcia, R.; Foschi, G.; Tortorella, S.; Valle, F.; Dallavalle, M.; Zerbetto, F.; Biscarini, F.

    2015-03-01

    The interactions of a biodegradable scaffold with cells or living tissues depend on the time-evolution of the nanoscale properties of the scaffold. We present an in situ quantitative study on the early-stage swelling and degradation of poly(lactic-co-glycolic acid) (PLGA). A novel metrology scheme based on force microscopy measurements of the patterns of PLGA nanostructures is developed to characterize the evolution of topography, volume and nanomechanical properties. The volume and nanoscale roughness show an oscillating behaviour during the first eight days of immersion; at a later stage, we observe a continuous decrease of the volume. The effective Young's modulus exhibits a monotonic decrease from an initial value of about 2.4 GPa down to 9 MPa at day 14. The oscillating behaviour of the volume before the onset of full degradation is explained by a coupled diffusion-swelling mechanism. The appearance of a second maximum in the volume evolution results from the competition between swelling and degradation.The interactions of a biodegradable scaffold with cells or living tissues depend on the time-evolution of the nanoscale properties of the scaffold. We present an in situ quantitative study on the early-stage swelling and degradation of poly(lactic-co-glycolic acid) (PLGA). A novel metrology scheme based on force microscopy measurements of the patterns of PLGA nanostructures is developed to characterize the evolution of topography, volume and nanomechanical properties. The volume and nanoscale roughness show an oscillating behaviour during the first eight days of immersion; at a later stage, we observe a continuous decrease of the volume. The effective Young's modulus exhibits a monotonic decrease from an initial value of about 2.4 GPa down to 9 MPa at day 14. The oscillating behaviour of the volume before the onset of full degradation is explained by a coupled diffusion-swelling mechanism. The appearance of a second maximum in the volume evolution results from

  10. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    PubMed

    Santiago, Jose A; Potashkin, Judith A

    2015-01-01

    Early diagnosis of Parkinson's disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  11. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    Abstract Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P

  12. Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

    SciTech Connect

    Ichimura, Ryohei; Mizukami, Sayaka; Takahashi, Miwa; Taniai, Eriko; Kemmochi, Sayaka; Mitsumori, Kunitoshi; Shibutani, Makoto

    2010-08-01

    To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter of Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

  13. Emission of spherical cesium-bearing particles from an early stage of the Fukushima nuclear accident

    PubMed Central

    Adachi, Kouji; Kajino, Mizuo; Zaizen, Yuji; Igarashi, Yasuhito

    2013-01-01

    The Fukushima nuclear accident released radioactive materials into the environment over the entire Northern Hemisphere in March 2011, and the Japanese government is spending large amounts of money to clean up the contaminated residential areas and agricultural fields. However, we still do not know the exact physical and chemical properties of the radioactive materials. This study directly observed spherical Cs-bearing particles emitted during a relatively early stage (March 14–15) of the accident. In contrast to the Cs-bearing radioactive materials that are currently assumed, these particles are larger, contain Fe, Zn, and Cs, and are water insoluble. Our simulation indicates that the spherical Cs-bearing particles mainly fell onto the ground by dry deposition. The finding of the spherical Cs particles will be a key to understand the processes of the accident and to accurately evaluate the health impacts and the residence time in the environment. PMID:23989894

  14. An Analysis of Risk and Function Information in Early Stage Design

    NASA Technical Reports Server (NTRS)

    Barrientos, Francesca; Tumer, Irem; Grantham, Katie; VanWie, Michael; Stone, Robert

    2005-01-01

    The concept of function offers a high potential for thinking and reasoning about designs as well as providing a common thread for relating together other design information. This paper focuses specifically on the relation between function and risk by examining how this information is addressed for a design team conducting early stage design for space missions. Risk information is decomposed into a set of key attributes which are then used to scrutinize the risk information using three approaches from the pragmatics sub-field of linguistics: i) Gricean, ii) Relevance Theory, and Functional Analysis. Results of this linguistics-based approach descriptively account for the context of designer communication with respect to function and risk, and offer prescriptive guidelines for improving designer communication.

  15. Early stage second-language learning improves executive control: evidence from ERP.

    PubMed

    Sullivan, Margot D; Janus, Monika; Moreno, Sylvain; Astheimer, Lori; Bialystok, Ellen

    2014-12-01

    A growing body of research has reported a bilingual advantage in performance on executive control tasks, but it is not known at what point in emerging bilingualism these advantages first appear. The present study investigated the effect of early stage second-language training on executive control. Monolingual English-speaking students were tested on a go-nogo task, sentence judgment task, and verbal fluency, before and after 6 months of Spanish instruction. The training group (n = 25) consisted of students enrolled in introductory Spanish and the control group (n = 30) consisted of students enrolled in introductory Psychology. After training, the Spanish group showed larger P3 amplitude on the go-nogo task and smaller P600 amplitude on the judgment task, indicating enhanced performance, with no changes for the control group and no differences between groups on behavioral measures. Results are discussed in terms of neural changes underlying executive control after brief second-language learning.

  16. Climate extremes can drive biological assemblages to early successional stages compared to several mild disturbances

    PubMed Central

    Sanz-Lázaro, Carlos

    2016-01-01

    Extreme climatic events have a major role in the structuring of biological communities, and their occurrence is expected to increase due to climate change. Here I use a manipulative approach to test the effects of extreme storm events on rocky mid-shore assemblages. This study shows that an extreme storm can cause more negative effects than several mild storms, primarily by bringing the biological assemblages towards early stages of succession. This finding contrasts with the effects of clustering of climatic events due to climate change, which are expected to mitigate its ecological impacts. Thus, the ecological consequences of climatic events that are influenced by climate change may have contrasting effects depending on the features that are considered. These results have relevant implications in the forecasting of the ecological consequences of climate change and should be considered when designing measures to mitigate its effects. PMID:27527612

  17. Toxic effects of magnesium oxide nanoparticles on early developmental and larval stages of zebrafish (Danio rerio).

    PubMed

    Ghobadian, Mehdi; Nabiuni, Mohammad; Parivar, Kazem; Fathi, Mojtaba; Pazooki, Jamileh

    2015-12-01

    Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies.

  18. [Quantitative histoenzymatic analysis of the adenohypophysis and adrenal cortex during the early stages of involution].

    PubMed

    Prochukhanov, R A; Rostovtseva, T I

    1977-11-01

    A method of quantitative histenzymatic analysis was applied for determination of the involution changes of the neuroendocrine system. The activity of NAD- and NADP-reductases, acid and alkaline phosphatases, glucose-6-phosphoric dehydrogenase, 3-OH-steroid-dehydrogenase, 11-hydroxysteroid dehydrogenases was investigated in the adenohypophysis and in the adrenal cortex of rats aged 4 and 12 months. There were revealed peculiarities attending the structural-metabolic provision of physiological reconstructions of the neuro-endocrine system under conditions of the estral cycle at the early involution stages. An initial reduction of the cell ular-vascular transport with the retention of the functional activity of the intracellular organoids was demonstrated in ageing animals.

  19. Early Stage Breast Cancer Treatments for Younger Medicare Beneficiaries with Different Disabilities

    PubMed Central

    Iezzoni, Lisa I; Ngo, Long H; Li, Donglin; Roetzheim, Richard G; Drews, Reed E; McCarthy, Ellen P

    2008-01-01

    Objective To explore how underlying disability affects treatments and outcomes of disabled women with breast cancer. Data Sources Surveillance, Epidemiology, and End Results program data, linked with Medicare files and Social Security Administration disability group. Study Design Ninety thousand two hundred and forty-three incident cases of early-stage breast cancer under age 65; adjusted relative risks and hazards ratios examined treatments and survival, respectively, for women in four disability groups compared with nondisabled women. Principal Findings Demographic characteristics, treatments, and survival varied among four disability groups. Compared with nondisabled women, those with mental disorders and neurological conditions had significantly lower adjusted rates of breast conserving surgery and radiation therapy. Survival outcomes also varied by disability type. Conclusions Compared with nondisabled women, certain subgroups of women with disabilities are especially likely to experience disparities in care for breast cancer. PMID:18479411

  20. Right Ventricular Outflow Tract Arrhythmias: Benign Or Early Stage Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia?

    PubMed

    Lin Md, Tina; Conti Md, Sergio; Cipolletta Md, Laura; Marino Md, Vittoria; Zucchetti Md, Martina; Russo Md, Eleonora; Pizzamiglio Md, Francesca; Al-Mohani Md, Ghaliah; Pala Be, Salvatore; Catto Be PhD, Valentina; Di Biase Md PhD, Luigi; Natale Md, Andrea; Tondo Md PhD Fesc, Claudio; Carbucicchio Md, Corrado

    2014-12-01

    Ventricular arrhythmias (VAs) arising from the right ventricular outflow tract (RVOT) are a common and heterogeneous entity. Idiopathic right ventricular arrhythmias (IdioVAs) are generally benign, with excellent ablation outcomes and long-term arrhythmia-free survival, and must be distinguished from other conditions associated with VAs arising from the right ventricle: the differential diagnosis with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is therefore crucial because VAs are one of the most important causes of sudden cardiac death (SCD) in young individuals even with early stage of the disease. Radiofrequency catheter ablation (RFCA) is a current option for the treatment of VAs but important differences must be considered in terms of indication, purposes and procedural strategies in the treatment of the two conditions. In this review, we comprehensively discuss clinical and electrophysiological features, diagnostic and therapeutic techniques in a compared analysis of these two entities.

  1. Polymeric composite devices for localized treatment of early-stage breast cancer

    PubMed Central

    Kan-Dapaah, Kwabena; Soboyejo, Wole

    2017-01-01

    For early-stage breast cancers mastectomy is an aggressive form of treatment. Therefore, there is a need for new treatment strategies that can enhance the use of lumpectomy by eliminating residual cancer cells with limited side effects to reduce local recurrence. Although, various radiotherapy-based methods have been developed, residual cells are found in 20–55% of the time at the first operation. Furthermore, some current treatment methods result in poor cosmesis. For the last decade, the authors have been exploring the use of polymeric composite materials in single and multi-modal implantable biomedical devices for post-operative treatment of breast cancer. In this paper, the concept and working principles of the devices, as well as selected results from experimental and numerical investigations, are presented. The results show the potential of the biomedical implants for cancer treatment. PMID:28245288

  2. Emission of spherical cesium-bearing particles from an early stage of the Fukushima nuclear accident.

    PubMed

    Adachi, Kouji; Kajino, Mizuo; Zaizen, Yuji; Igarashi, Yasuhito

    2013-01-01

    The Fukushima nuclear accident released radioactive materials into the environment over the entire Northern Hemisphere in March 2011, and the Japanese government is spending large amounts of money to clean up the contaminated residential areas and agricultural fields. However, we still do not know the exact physical and chemical properties of the radioactive materials. This study directly observed spherical Cs-bearing particles emitted during a relatively early stage (March 14-15) of the accident. In contrast to the Cs-bearing radioactive materials that are currently assumed, these particles are larger, contain Fe, Zn, and Cs, and are water insoluble. Our simulation indicates that the spherical Cs-bearing particles mainly fell onto the ground by dry deposition. The finding of the spherical Cs particles will be a key to understand the processes of the accident and to accurately evaluate the health impacts and the residence time in the environment.

  3. Climate extremes can drive biological assemblages to early successional stages compared to several mild disturbances

    NASA Astrophysics Data System (ADS)

    Sanz-Lázaro, Carlos

    2016-08-01

    Extreme climatic events have a major role in the structuring of biological communities, and their occurrence is expected to increase due to climate change. Here I use a manipulative approach to test the effects of extreme storm events on rocky mid-shore assemblages. This study shows that an extreme storm can cause more negative effects than several mild storms, primarily by bringing the biological assemblages towards early stages of succession. This finding contrasts with the effects of clustering of climatic events due to climate change, which are expected to mitigate its ecological impacts. Thus, the ecological consequences of climatic events that are influenced by climate change may have contrasting effects depending on the features that are considered. These results have relevant implications in the forecasting of the ecological consequences of climate change and should be considered when designing measures to mitigate its effects.

  4. The early stage wheel fatigue crack detection using eddy current pulsed thermography

    NASA Astrophysics Data System (ADS)

    Peng, Jianping; Zhang, Kang; Yang, Kai; He, Zhu; Zhang, Yu; Peng, Chaoyong; Gao, Xiaorong

    2017-02-01

    The in-service wheel-set quality is one of critical challenges for railway safety, especially for the high-speed train. The defect in wheel tread, initiated by rolling contact fatigue (RCF) damage, is one of the most significant phenomena and has serious influence on rail industry. Eddy current pulsed thermography is studied to compensate the UT method for detection these early stage of fatigue cracks in wheel tread surface. This paper proposes approximately uniform magnetic field, excited by Helmholtz coils, based pulsed eddy current thermography to achieve open-view image and meet the irregular surface in wheel tread through numerical way. Some features are extracted and studied also to quantify the fatigue crack in term of eddy current pulsed thermography. The proposed method enhances the capability for cracks detection and quantitative evaluation compared with previous NDT method in railway.

  5. Placental transport of lindane during early and late stages of gestation in rats

    SciTech Connect

    Khanna, R.N.; Kunwar, K.; Gupta, R.; Gupta, G.S.D. )

    1991-10-01

    Lindane (gamma-isomer of hexachlorocyclohexane, gamma-HCH), an organochlorine pesticide, is widely used as an agricultural pesticide especially in developing countries. Human exposure is likely because of its use in some pharmaceutical preparations and in public health for pest control purpose. It has been detected in human milk and fat samples in India and in many developed countries. The accumulation of lindane over a long period in fat samples and its presence in milk suggests that the human fetus may be exposed to lindane at some time during gestation from the maternal tissue stores. The present study was, therefore, undertaken to determine the placental transfer of lindane in rats during early and late stages of gestation.

  6. Kinetic study of model reactions in the gas phase at the early stage of coke formation

    SciTech Connect

    Nohara, D.; Sakai, T. )

    1992-01-01

    This paper reports that the most probable gas-phase reactions at the early stage of coke formation were elucidated by kinetic study on the model reactions adopted for formation of cyclic compounds and growth of ring. It was revealed that the formation and growth of ring proceeded mainly through cycloaddition of butadiene or allyl radicals to unsaturated hydrocarbons at relatively low temperatures ({approximately}600{degrees}C), i.e., through a Diels-Alder type reaction. On the other hand, such growth of ring as formation of biphenyl accompanying dehydrogenation from benzene can proceed only at the higher temperatures. It was also revealed that in the growth of the ring, cycloaddition of butadiene favors a cyclic olefin molecule that possesses a nonconjugated double bond and a nearly planar structure.

  7. State of the art of diagnostic technology for early-stage melanoma.

    PubMed

    Guitera, Pascale; Menzies, Scott W

    2011-05-01

    In the past few decades, rapid improvements in noninvasive optical technologies have revolutionized the diagnosis of early-stage melanoma. Current knowledge and limitations of these tools will be reviewed in this article. Dermoscopy has been recognized as the 'gold standard' in the screening phase. Digital dermoscopy monitoring and total-body photography are used to identify so-called 'featureless' melanoma only on the criteria of change over time. Automated instruments, as well as optical and nonmorphological methods, are still under development, and offer many opportunities to improve the speed and accuracy of the diagnosis of melanoma and/or to reduce the need for expertise. Despite a penetration depth limited to the upper dermis, the quasi-histological imaging achieved by in vivo reflectance confocal microscopy has been demonstrated to significantly aid diagnostic accuracy for selected melanocytic lesions. Future perspectives on diagnostic instrumentation will also be explored.

  8. [The rural polyclinic in the early stage of the People's Republic of China.].

    PubMed

    Li, De-Cheng; Jin, Xu-Zhong

    2009-11-01

    The polyclinic is one type of medical organization of mutual assistance and cooperation of a collective nature, which was founded based on the integration of rural original medical and health resources in the early stage of the People's Republic of China. The polyclinic played a particular role in resolving the extreme shortage of rural medical resources and medicines at that time and promoting the sanitary and anti-epidemic situation in rural communities. This laid a foundation for the three-level network of care and medical prevention. However it did not change the traditional mode of healthcare and medical work so that is also failed in solving the problems of shortage of medicines in rural areas.

  9. Hypofractionated radiation therapy in the treatment of early-stage breast cancer.

    PubMed

    Freedman, Gary M

    2012-02-01

    Hypofractionated radiation refers to the use of fewer, larger-dose radiation treatments that are usually given over a shorter time period compared to conventional radiation fraction sizes. Randomized trials of hypofractionated whole breast irradiation (WBI) have demonstrated comparable outcomes as conventional fractionation. For a higher-risk population for local recurrence, a phase 3 trial by the Radiation Therapy Oncology Group (RTOG) is currently studying hypofractionated WBI with a concurrent tumor bed boost over 3 weeks. Accelerated partial breast irradiation limits radiation to the region of the tumor bed for 1-3 weeks and is the subject of an ongoing randomized trial by the National Surgical Breast and Bowel Project and RTOG. Questions remain for hypofractionation about optimal patient selection, radiation techniques, and the risk of late toxicity. But results from current trials could make hypofractionation more widely accepted for patients with early-stage breast cancer.

  10. Early stage of critical clusters growth in phenomenological and molecular dynamics simulation models

    NASA Astrophysics Data System (ADS)

    Puzyrewski, Romuald; Rybicki, Jarosław; Białoskórski, Michał

    2006-12-01

    The growth of critical clusters is discussed in the paper according to the classical and molecular dynamics (MD) approaches. A new formula for molecule numbers in critical clusters has been derived within the framework of the classical approach. A set of equations controlling the early stage of growth in a neighborhood of a critical size is presented. As far as molecular dynamics simulation is concerned, a computational technique based on the DL_POLY code is described in brief. Computation results are presented concerning cluster formation of H 2O vapor, distribution of clusters versus time, cluster growth and radial density distribution of isolated clusters. A comparison with the classical results is made for a case of dense vapor, where the mechanism of strong condensation is predominant. The Hertz-Knudsen formula seems to be verified by the molecular dynamics results.

  11. Early stage biliary and intrahepatic migration of Opisthorchis viverrini in the golden hamster.

    PubMed

    Nithikathkul, C; Tesana, S; Sithithaworn, P; Balakanich, S

    2007-03-01

    In Thailand, infection with the liver fluke Opisthorchis viverrini is a serious health problem, with over 8.6 million human infections each year. Early stage biliary intrahepatic migration and infection of O. viverrini in the Syrian golden hamster were used to study the growth and development of this fluke. Fifty metacercariae of O. viverrini were introduced into each hamster by gastric intubation. Worms were found to migrate rapidly from the stomach to the gall bladder and hepatic duct, where they remained in relatively constant numbers until the end of week 8. Sexual development of worms was rapid, with full development of the uterus and testes by one and one half weeks and the appearance of eggs in the uterus by the beginning of the third week of infection. Worm growth as indicated by body length had ceased by week 8. Hamsters demonstrated development of a full reproductive cycle with in three to four weeks, and this generation continued until 8 weeks.

  12. [Extracranial stereotactic radiotherapy for early-stage non-small cell lung cancer and oligometastases].

    PubMed

    Riesterer, Oliver

    2013-10-16

    Stereotactic body radiotherapy (SBRT) is a new radiation technique that combines improvements in radiotherapy planning, intensity modulation and image guidance. The use of SBRT enables radiotherapy to be delivered instead of in six weeks in only a few days and with ablative total dose. Prospective phase II studies in patients with inoperable early stage non-small cell lung cancer demonstrate that the use of SBRT results in local control rates of 85-95% with acceptable toxicity. SBRT is also increasingly used for treatment of metastases in the lung, liver, retroperitoneum and in bones. Because SBRT enables a locally curative dose to be delivered in a time efficient manner this technique also opens up new perspectives for the treatment of patients with oligometastases.

  13. Late-Stage Fluvial Erosion in a Changing Climate on Early Mars

    NASA Astrophysics Data System (ADS)

    Irwin, R. P.; Matsubara, Y.

    2013-12-01

    The decline of heavy bombardment in the solar system coincided with incision of many branching fluvial valleys in the martian highlands. However, these valley networks are underdeveloped relative to typical terrestrial networks, suggesting that valley incision was geologically brief or slow on Mars. Most previous studies have attributed the end of martian fluvial erosion to a monotonic decline of the atmosphere and climate around the Noachian/Hesperian transition. Identification of fluvial valleys on some younger surfaces, including Hesperian volcanoes, and the occurrence of morphologically pristine and degraded reaches in the same valley networks challenged the simplicity of this model. More recently, fluvial valleys and deposits have been recognized on a variety of Hesperian surfaces, including the plateau around Valles Marineris, certain impact craters, and the crustal dichotomy boundary scarp. The extent to which this late-stage erosion represents localized event floods or more widely distributed precipitation and runoff remains to be determined. To evaluate whether Hesperian resurfacing processes were concurrent with (and may have caused) late-stage fluvial erosion, we are identifying any geologically rare or long-lived events that occurred between significant resurfacing events and fluvial erosion of those surfaces. In a variety of locations, we have identified small primary craters that formed between local resurfacing and fluvial dissection of those surfaces, suggesting a gap in time between resurfacing and dissection. These small, otherwise fresh craters have rims or ejecta that were incised by late-stage flows. In other cases, thick stratified deposits accumulated on Hesperian surfaces, and those deposits were later dissected by running water. We also found that highland intercrater plains generally have Early to mid-Hesperian crater populations at diameters less than about 4 km. All smaller primary and secondary craters from the Noachian Period were

  14. EARLY-STAGE DESIGN AND EVALUATION FOR NUCLEAR POWER PLANT CONTROL ROOM UPGRADES

    SciTech Connect

    Ronald L. Boring; Jeffrey C. Joe; Thomas A. Ulrich; Roger T. Lew

    2015-03-01

    As control rooms are modernized with new digital systems at nuclear power plants, it is necessary to evaluate operator performance with these systems as part of a verification and validation process. While there is regulatory and industry guidance for some modernization activities, there are no well defined standard processes or predefined metrics available for assessing what is satisfactory operator interaction with new systems, especially during the early design stages. This paper proposes a framework defining the design process and metrics for evaluating human system interfaces as part of control room modernization. The process and metrics are generalizable to other applications and serve as a guiding template for utilities undertaking their own control room modernization activities.

  15. Dose-Dependent Early Life Stage Toxicities in Xenopus laevis Exposed In Ovo to Selenium.

    PubMed

    Massé, Anita J; Muscatello, Jorgelina R; Janz, David M

    2015-11-17

    Selenium (Se) is a developmental toxicant in oviparous vertebrates. The adverse reproductive effects of Se toxicity have been predominantly investigated in fishes and birds with only a few studies focusing on amphibians. The objective of this study was to determine tissue-based toxicity thresholds for early life stage Se toxicities in Xenopus laevis as a consequence of in ovo exposure through maternal transfer of dietary Se. Following a 68-day dietary exposure to food augmented with l-selenomethionine (SeMet) at measured concentrations of 0.7 (control), 10.9, 30.4, or 94.2 μg Se/g dry mass (d.m.), adult female X. laevis were bred with untreated males, and resulting embryos were incubated until 5 days postfertilization (dpf). The measured Se concentrations in eggs were 1.6, 10.8, 28.1, and 81.7 μg Se/g d.m., respectively. No biologically significant effects were observed on fertilization success, hatchability, or mortality in offspring. Frequency and severity of morphological abnormalities were significantly greater in 5 dpf tadpoles from the highest exposure group when compared to the control, with eye lens abnormalities being the most prominent of all abnormalities. The estimated EC10 value for frequency of total early life stage abnormalities was 44.9 μg Se/g egg d.m., which suggests that this amphibian species is less sensitive to in ovo Se exposure than most of the fish species studied to date.

  16. Similarity ratio analysis for early stage fault detection with optical emission spectrometer in plasma etching process.

    PubMed

    Yang, Jie; McArdle, Conor; Daniels, Stephen

    2014-01-01

    A Similarity Ratio Analysis (SRA) method is proposed for early-stage Fault Detection (FD) in plasma etching processes using real-time Optical Emission Spectrometer (OES) data as input. The SRA method can help to realise a highly precise control system by detecting abnormal etch-rate faults in real-time during an etching process. The method processes spectrum scans at successive time points and uses a windowing mechanism over the time series to alleviate problems with timing uncertainties due to process shift from one process run to another. A SRA library is first built to capture features of a healthy etching process. By comparing with the SRA library, a Similarity Ratio (SR) statistic is then calculated for each spectrum scan as the monitored process progresses. A fault detection mechanism, named 3-Warning-1-Alarm (3W1A), takes the SR values as inputs and triggers a system alarm when certain conditions are satisfied. This design reduces the chance of false alarm, and provides a reliable fault reporting service. The SRA method is demonstrated on a real semiconductor manufacturing dataset. The effectiveness of SRA-based fault detection is evaluated using a time-series SR test and also using a post-process SR test. The time-series SR provides an early-stage fault detection service, so less energy and materials will be wasted by faulty processing. The post-process SR provides a fault detection service with higher reliability than the time-series SR, but with fault testing conducted only after each process run completes.

  17. Magnetic fields during the early stages of massive star formation - I. Accretion and disc evolution

    NASA Astrophysics Data System (ADS)

    Seifried, D.; Banerjee, R.; Klessen, R. S.; Duffin, D.; Pudritz, R. E.

    2011-10-01

    We present simulations of collapsing 100 M⊙ mass cores in the context of massive star formation. The effect of variable initial rotational and magnetic energies on the formation of massive stars is studied in detail. We focus on accretion rates and on the question under which conditions massive Keplerian discs can form in the very early evolutionary stage of massive protostars. For this purpose, we perform 12 simulations with different initial conditions extending over a wide range in parameter space. The equations of magnetohydrodynamics (MHD) are solved under the assumption of ideal MHD. We find that the formation of Keplerian discs in the very early stages is suppressed for a mass-to-flux ratio normalized to the critical value μ below 10, in agreement with a series of low-mass star formation simulations. This is caused by very efficient magnetic braking resulting in a nearly instantaneous removal of angular momentum from the disc. For weak magnetic fields, corresponding to μ≳ 10, large-scale, centrifugally supported discs build up with radii exceeding 100 au. A stability analysis reveals that the discs are supported against gravitationally induced perturbations by the magnetic field and tend to form single stars rather than multiple objects. We find protostellar accretion rates of the order of a few 10-4 M⊙ yr-1 which, considering the large range covered by the initial conditions, vary only by a factor of ˜ 3 between the different simulations. We attribute this fact to two competing effects of magnetic fields. On the one hand, magnetic braking enhances accretion by removing angular momentum from the disc thus lowering the centrifugal support against gravity. On the other hand, the combined effect of magnetic pressure and magnetic tension counteracts gravity by exerting an outward directed force on the gas in the disc thus reducing the accretion on to the protostars.

  18. Genomic Prediction of Single Crosses in the Early Stages of a Maize Hybrid Breeding Pipeline

    PubMed Central

    Kadam, Dnyaneshwar C.; Potts, Sarah M.; Bohn, Martin O.; Lipka, Alexander E.; Lorenz, Aaron J.

    2016-01-01

    Prediction of single-cross performance has been a major goal of plant breeders since the beginning of hybrid breeding. Recently, genomic prediction has shown to be a promising approach, but only limited studies have examined the accuracy of predicting single-cross performance. Moreover, no studies have examined the potential of predicting single crosses among random inbreds derived from a series of biparental families, which resembles the structure of germplasm comprising the initial stages of a hybrid maize breeding pipeline. The main objectives of this study were to evaluate the potential of genomic prediction for identifying superior single crosses early in the hybrid breeding pipeline and optimize its application. To accomplish these objectives, we designed and analyzed a novel population of single crosses representing the Iowa Stiff Stalk synthetic/non-Stiff Stalk heterotic pattern commonly used in the development of North American commercial maize hybrids. The performance of single crosses was predicted using parental combining ability and covariance among single crosses. Prediction accuracies were estimated using cross-validation and ranged from 0.28 to 0.77 for grain yield, 0.53 to 0.91 for plant height, and 0.49 to 0.94 for staygreen, depending on the number of tested parents of the single cross and genomic prediction method used. The genomic estimated general and specific combining abilities showed an advantage over genomic covariances among single crosses when one or both parents of the single cross were untested. Overall, our results suggest that genomic prediction of single crosses in the early stages of a hybrid breeding pipeline holds great potential to redesign hybrid breeding and increase its efficiency. PMID:27646704

  19. Population genomics of a symbiont in the early stages of a pest invasion.

    PubMed

    Brown, Amanda M V; Huynh, Lynn Y; Bolender, Caitlin M; Nelson, Kelly G; McCutcheon, John P

    2014-03-01

    Invasive species often depend on microbial symbionts, but few studies have examined the evolutionary dynamics of symbionts during the early stages of an invasion. The insect Megacopta cribraria and its bacterial nutritional symbiont Candidatus Ishikawaella capsulata invaded the southeastern US in 2009. While M. cribraria was initially discovered on wild kudzu plants, it was found as a pest on soybeans within 1 year of infestation. Because prior research suggests Ishikawaella confers the pest status--that is, the ability to thrive on soybeans--in some Megacopta species, we performed a genomic study on Ishikawaella from US. Megacopta cribraria populations to understand the role of the symbiont in driving host plant preferences. We included Ishikawaella samples collected in the first days of the invasion in 2009 and from 23 locations across the insect's 2011 US range. The 0.75 Mb symbiont genome revealed only 47 fixed differences from the pest-conferring Ishikawaella in Japan, with only one amino acid change in a nutrition-provisioning gene. This similarity, along with a lack of fixed substitutions in the US symbiont population, indicates that Ishikawella likely arrived in the US capable of being a soybean pest. Analyses of allele frequency changes between 2009 and 2011 uncover signatures of both positive and negative selection and suggest that symbionts on soybeans and kudzu experience differential selection for genes related to nutrient provisioning. Our data reveal the evolutionary trajectory of an important insect-bacteria symbiosis in the early stages of an invasion, highlighting the role microbial symbionts may play in the spread of invasive species.

  20. Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

    PubMed

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line.

  1. Partial Breast Irradiation Versus Whole Breast Radiotherapy for Early-Stage Breast Cancer: A Decision Analysis

    SciTech Connect

    Sher, David J.; Wittenberg, Eve; Taghian, Alphonse G.; Bellon, Jennifer R.; Punglia, Rinaa S.

    2008-02-01

    Purpose: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. Results: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. Conclusions: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.

  2. Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

    SciTech Connect

    Woolston, Caroline M.; Al-Attar, Ahmad; Storr, Sarah J.; Ellis, Ian O.; Morgan, David A.L.; Martin, Stewart G.

    2011-04-01

    Purpose: Early-stage invasive breast cancer patients have commonly undergone breast-conserving surgery and radiotherapy. In a large majority of these patients, the treatment is effective; however, a proportion will develop local recurrence. Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Therefore, the expression of redox proteins was examined in tumor specimens from this defined cohort to determine whether such expression could predict response. Methods and Materials: The nuclear and cytoplasmic expression of nine redox proteins (glutathione, glutathione reductase, glutaredoxin, glutathione peroxidase 1, 3, and 4, and glutathione S-transferase-{theta}, -{pi}, and -{alpha}) was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors. Results: A high cytoplasmic expression of glutathione S-transferase-{theta} significantly correlated with a greater risk of local recurrence (p = .008) and, when combined with a low nuclear expression (p = .009), became an independent predictive factor (p = .002) for local recurrence. High cytoplasmic expression of glutathione S-transferase-{theta} also correlated with a worse overall survival (p = .009). Low nuclear and cytoplasmic expression of glutathione peroxidase 3 (p = .002) correlated with a greater risk of local recurrence and was an independent predictive factor (p = .005). These proteins did not correlate with tumor grade, suggesting their function might be specific to the regulation of oxidative stress rather than alterations of tumor phenotype. Only nuclear (p = .005) and cytoplasmic (p = .001) expression of glutathione peroxidase 4 correlated with the tumor grade. Conclusions: Our results support the use of redox protein expression, namely glutathione S-transferase-{theta} and glutathione peroxidase 3, to predict the response to radiotherapy in early-stage breast cancer patients. If incorporated into

  3. Trust during the early stages of the 2009 H1N1 pandemic.

    PubMed

    Freimuth, Vicki S; Musa, Don; Hilyard, Karen; Quinn, Sandra Crouse; Kim, Kevin

    2014-01-01

    Distrust of the government often stands in the way of cooperation with public health recommendations in a crisis. The purpose of this article is to describe the public's trust in government recommendations during the early stages of the H1N1 pandemic and to identify factors that might account for these trust levels. The authors surveyed 1,543 respondents about their experiences and attitudes related to H1N1 influenza between June 3, 2009, and July 6, 2009, during the first wave of the pandemic using the Knowledge Networks online panel. This panel is representative of the U.S. population and uses a combination of random digit dialing and address-based probability sampling frames covering 99% of the U.S. household population to recruit participants. To ensure participation of low-income individuals and those without Internet access, Knowledge Networks provides hardware and access to the Internet if needed. Measures included standard demographics, a trust scale, trust ratings for individual spokespersons, involvement with H1N1, experience with H1N1, and past discrimination in health care. The authors found that trust of government was low (2.3 out of 4) and varied across demographic groups. Blacks and Hispanics reported higher trust in government than did Whites. Of the spokespersons included, personal health professionals received the highest trust ratings and religious leaders the lowest. Attitudinal and experience variables predicted trust better than demographic characteristics. Closely following the news about the flu virus, having some self-reported knowledge about H1N1, self-reporting of local cases, and previously experiencing discrimination were the significant attitudinal and experience predictors of trust. Using a second longitudinal survey, trust in the early stages of the pandemic predicted vaccine acceptance later but only for White, non-Hispanic individuals.

  4. Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

    PubMed Central

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

  5. Early Stage Biomineralization in the Periostracum of the ‘Living Fossil’ Bivalve Neotrigonia

    PubMed Central

    Checa, Antonio G.; Salas, Carmen; Harper, Elizabeth M.; Bueno-Pérez, Juan de Dios

    2014-01-01

    A detailed investigation of the shell formation of the palaeoheterodont ‘living fossil’ Neotrigonia concentrated on the timing and manufacture of the calcified ‘bosses’ which stud the outside of all trigonioid bivalves (extant and fossil) has been conducted. Electron microscopy and optical microscopy revealed that Neotrigonia spp. have a spiral-shaped periostracal groove. The periostracum itself is secreted by the basal cell, as a thin dark pellicle, becoming progressively transformed into a thin dark layer by additions of secretions from the internal outer mantle fold. Later, intense secretion of the internal surface of the outer mantle fold forms a translucent layer, which becomes transformed by tanning into a dark layer. The initiation of calcified bosses occurred at a very early stage of periostracum formation, deep within the periostracal groove immediately below the initialmost dark layer. At this stage, they consist of a series of polycyclically twinned crystals. The bosses grow as the periostracum traverse through the periostracal groove, in coordination with the thickening of the dark periostracal layer and until, upon reaching the mantle edge, they impinge upon each other and become transformed into large prisms separated by dark periostracal walls. In conclusion, the initial bosses and the external part of the prismatic layer are fully intraperiostracal. With later growth, the prisms transform into fibrous aggregates, although the details of the process are unknown. This reinforces the relationships with other groups that have the ability to form intraperiostracal calcifications, for example the unionoids with which the trigonioids form the clade Paleoheterodonta. The presence of similar structures in anomalodesmatans and other euheterodonts raises the question of whether this indicates a relationship or represents a convergence. The identification of very early calcification within an organic sheet has interesting implications for our

  6. Sildenafil and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.

    PubMed

    Binns-Loveman, Karen M; Kaplowitz, Mark R; Fike, Candice D

    2005-07-01

    Devising therapies that might prevent the onset or progression of pulmonary hypertension in newborns has received little attention. Our major objective was to determine whether sildenafil, a selective phosphodiesterase inhibitor, prevents the development of an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs. Another objective was to determine whether sildenafil causes pulmonary vasodilation without systemic vasodilation in piglets with chronic pulmonary hypertension. Piglets were raised in room air (control, n = 5) or 10-11% O(2) (hypoxic, n = 17) for 3 days. Some piglets (n = 4) received oral sildenafil, 12 mg/kg/day, throughout exposure to hypoxia. All piglets were anesthetized and catheterized, and pulmonary arterial pressure (Ppa), pulmonary wedge pressure (Pw), aortic pressure (Ao), and cardiac output (CO) were measured. Then for some piglets raised in hypoxia for 3 days, a single oral sildenafil dose (3 mg/kg, n = 6) or placebo (n = 5) was given, and hemodynamic measurements were repeated. For piglets raised in hypoxia for 3 days, mean Ppa and calculated PVR were elevated above respective values in control piglets. Mean Ppa and PVR did not differ between piglets that received sildenafil throughout exposure to hypoxia and those that did not. For piglets with chronic hypoxia-induced pulmonary hypertension that received a single oral dose of sildenafil, mean Ppa and PVR decreased, while mean Pw, CO, mean Ao, and systemic vascular resistance remained the same. All hemodynamic measurements were unchanged after placebo. Oral sildenafil did not influence the early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets. However, a single oral dose of sildenafil caused pulmonary vasodilation, without systemic vasodilation, in piglets with chronic hypoxia-induced pulmonary hypertension, which may have therapeutic implications.

  7. Hyper-connectivity of the Thalamus in during Early Stages following Mild Traumatic Brain Injury

    PubMed Central

    Sours, Chandler; George, Elijah O.; Zhuo, Jiachen; Roys, Steven; Gullapalli, Rao P.

    2015-01-01

    The thalamo-cortical resting state functional connectivity of 7 sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6±3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self-reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work. PMID:26153468

  8. Comparing stochastic differential equations and agent-based modelling and simulation for early-stage cancer.

    PubMed

    Figueredo, Grazziela P; Siebers, Peer-Olaf; Owen, Markus R; Reps, Jenna; Aickelin, Uwe

    2014-01-01

    There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm.

  9. URINE miRNAs: POTENTIAL BIOMARKERS FOR MONITORING PROGRESION OF EARLY STAGES OF DIABETIC NEPHROPATHY

    PubMed Central

    Yang, Yeyi; Xiao, Li; Li, Jun; Kanwar, Yashpal S.; Liu, Fuyou; Sun, Lin

    2013-01-01

    With a steep increase in the incidence of type 1 and 2 diabetes globally, diabetic nephropathy (DN) has now become the leading cause of renal failure in the world. There are no suitable biomarkers for the diagnosis of early stages of DN. In recent years, tremendous efforts are being made worldwide to delineate the role of micro RNAs in the pathogenesis of DN. Circulating miRNAs in serum, plasma, urine and other body fluids, which reflect a response to various pathophysiological stresses, are being investigated in the context of diabetic nephropathy. Delineation of the changes in miRNA levels in patients with DN may lead to a better understanding of the progression of the disease. We present here an exhaustive survey of the miRNA literature, highlighting various studies performed over the last decade. The aim is to assess if changes in various miRNAs could correlate with the progression of diabetic nephropathy. Based on the survey, we found that miRNA-377, miRNA-192, miRNA-216/217 and miRNA-144 are increased in body fluids of patients with DN, while miRNA-21 and miRNA-375 are decreased. Overall, there are a very few miRNAs that are kidney specific, and although significant differences were observed in the urinary excretion of certain miRNAs, they were not correlative to their levels in the blood or plasma. Thus, it is completely plausible that urine-specific miRNAs could serve as novel biomarkers for the diagnosis of early stages of diabetic nephropathy. PMID:23683774

  10. Early experience with laparoscopic sleeve gastrectomy as a single-stage bariatric procedure.

    PubMed

    Lewis, Catherine E; Dhanasopon, Andrew; Dutson, Erik P; Mehran, Amir

    2009-10-01

    Laparoscopic sleeve gastrectomy (LSG) as a single-stage restrictive bariatric procedure is becoming increasingly popular, especially in patients who are high risk and/or superobese. Between November 21, 2006, and September 30, 2008, 42 patients underwent LSG at our institution. Average age was 47 +/- 11 years, average body mass index was 54 +/- 10 kg/m2, and 62 per cent were female. Preoperative indications for LSG included contraindication to laparoscopic Roux-en-Y gastric bypass (n = 11), severe coronary artery disease and/or congestive heart failure (n = 3), significant liver disease (n = 3), and patient preference (n = 4). Intraoperative indications for LSG included a foreshortened mesentery with inability to create a gastrojejunostomy (n = 13), extensive adhesions (n = 5), and intraoperative findings concerning for cirrhosis (n = 3). Twelve complications occurred in six patients: laparoscopic to open conversion (n = 1), reoperation (n = 3), nosocomial pneumonia (n = 1), wound infection (n = 1), bleeding (n = 1), pulmonary embolus (n = 1), readmission (n = 3), and superior splenic pole infarction. There was one death resulting from pulmonary embolism that occurred 2 weeks postoperatively. Preliminary excess body weight loss at 3, 6, 9, and 12 months was 29, 32 t, 38, and 30 per cent, respectively, and many patients had improvement or resolution of obesity-related comorbidities. Early review of our experience demonstrates that LSG may be an effective single-stage bariatric procedure. Additional follow up will be necessary to better define its long-term safety and efficacy.

  11. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    PubMed

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-07

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  12. Early stage reversed crystal growth of zeolite A and its phase transformation to sodalite.

    PubMed

    Greer, Heather; Wheatley, Paul S; Ashbrook, Sharon E; Morris, Russell E; Zhou, Wuzong

    2009-12-16

    Microstructural analysis of the early stage crystal growth of zeolite A in hydrothermal synthetic conditions revealed a revised crystal growth route from surface to core in the presence of the biopolymer chitosan. The mechanism of this extraordinary crystal growth route is discussed. In the first stage, the precursor and biopolymer aggregated into amorphous spherical particles. Crystallization occurred on the surface of these spheres, forming the typical cubic morphology associated with zeolite A with a very thin crystalline cubic shell and an amorphous core. With a surface-to-core extension of crystallization, sodalite nanoplates were crystallized within the amorphous cores of these zeolite A cubes, most likely due to an increase of pressure. These sodalite nanoplates increased in size, breaking the cubic shells of zeolite A in the process, leading to the phase transformation from zeolite A to sodalite via an Ostwald ripening process. Characterization of specimens was performed using scanning electron microscopy and transmission electron microscopy, supported by other techniques including X-ray diffraction, solid-state NMR, and N(2) adsorption/desorption.

  13. Improving website accessibility for people with early-stage dementia: a preliminary investigation.

    PubMed

    Freeman, E D; Clare, Linda; Savitch, Nada; Royan, Lindsay; Litherland, Rachael; Lindsay, Margot

    2005-09-01

    This study, conducted collaboratively with five men who have a diagnosis of early-stage Alzheimer's disease (AD), is the first stage of a formative research project aimed at developing a new website for people with dementia. Recommendations derived from a literature review of the implications of dementia-related cognitive changes for website design were combined with general web accessibility guidelines to provide a basis for the initial design of a new website. This website was compared with an equivalent site, containing the same information but based on an existing design, in terms of accessibility, ease of use, and user satisfaction. Participants were very satisfied with both sites, but responses did indicate some specific areas where one site was preferred over another. Observational data highlighted significant strengths of the new site as well as some limitations, and resulted in clear recommendations for enhancing the design. In particular, the study suggested that limiting the size of web pages to the amount of information that can be displayed on a computer screen at any one time could reduce the level of difficulty encountered by the participants. The results also suggested the importance of reducing cognitive load through limiting the number of choices required at any one time, the very opposite of the ethos of much website design.

  14. Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer.

    PubMed

    Han, Jun; Meng, Qingyang; Xi, Qiulei; Zhang, Yongxian; Zhuang, Qiulin; Han, Yusong; Jiang, Yi; Ding, Qiurong; Wu, Guohao

    2016-01-01

    Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

  15. Stereotactic radiotherapy for early stage non-small cell lung cancer

    PubMed Central

    Badellino, Serena; Filippi, Andrea Riccardo

    2015-01-01

    Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice. PMID:26157674

  16. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

    PubMed Central

    Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    Objectives This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. Methods The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Results Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Conclusions Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification. PMID:27861522

  17. Radiation therapy for early stage unfavorable Hodgkin lymphoma: is dose reduction feasible?

    PubMed

    Laskar, Siddhartha; Kumar, Deepak P; Khanna, Nehal; Menon, Hari; Sengar, Manju; Arora, Brijesh; Gujral, Sumeet; Shet, Tanuja; Sridhar, Epari; Rangarajan, Venkatesh; Muckaden, Mary Ann; Nair, Reena; Banavali, Shripad

    2014-10-01

    One hundred and fifty-one patients aged between 3 and 70 years with early stage unfavorable Hodgkin lymphoma were included. Patients received 4-6 cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and involved field radiation therapy (IFRT). The most common histology was mixed cellularity (43%). The majority had stage IIAX disease. IFRT doses were 25.2 Gy/14 fractions and 34.2 Gy/19 fractions for adults with a complete response (CR) and partial response (PR), respectively, while the doses were 19.8 Gy/11 fractions and 30.6 Gy/17 fractions, respectively, for children. After 60 months (median), the 10-year progression-free survival (PFS) and overall survival (OS) were 88.4% and 93.2%, respectively. On univariate analysis, prognostic factors with significant impact on PFS were age ≥ 18 years, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) histology, extranodal disease and response to treatment. Extranodal disease had a significant impact on OS. On multivariate analysis, NLPHL histology (p = 0.001) and response at 3 months (p = 0.000) had a significant impact on PFS. There were no in-field relapses in patients with bulky disease receiving RT doses > 25.2 Gy. Chemotherapy related acute pulmonary toxicity was documented in 21.4% and 4.8% of patients after six and four cycles of ABVD chemotherapy (p = 0.041). Four cycles of ABVD and reduced dose IFRT resulted in optimal outcomes.

  18. Results and survival after photodynamic therapy in early-stage esophageal carcinoma

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Mancini, Andrea; Dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

    1996-01-01

    From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

  19. Surgical treatment preferences in Chinese-American women with early-stage breast cancer.

    PubMed

    Killoran, Moira; Moyer, Anne

    2006-11-01

    Breast-conserving treatment (BCT) is considered preferable to radical or modified radical mastectomy (MRM) for most women diagnosed with early-stage breast cancer. Studies have found that Chinese-American women are more likely to be treated with MRM, regardless of age or stage of disease. The central question posed in this study is: what are the cultural factors that influence the selection of treatments by Chinese-American patients and the presentation of treatment options by providers? Focused group discussions, semi-structured interviews, and ethnographic observations were conducted with 69 Chinese-American women and 14 health professionals. Results indicated that (1) many Chinese-American women, regardless of age, migration status, education, and income level, expressed a preference for MRM because it was seen as safer; (2) this was primarily a communal belief that even women who had BCT felt pressure to conform to; (3) some women felt pressured into the BCT decision by their physician and/or were unhappy with their choice; (4) patient and physician bias and difficulties with translation issues and supplemental materials all led to cross-cultural miscommunication; and (5) this miscommunication was cited as a reason for (a) not completing treatment regimes or (b) drastic changes in the treatment selected.

  20. Hematopoietic cell crisis: An early stage of evolving myeloid leukemia following radiation exposure

    SciTech Connect

    Seed, T.M.

    1990-01-01

    Under select radiological conditions, chronic radiation exposure elicits a high incidence of myeloproliferative disease, principally myeloid leukemia (ML), in beagles. Previously we demonstrated that for full ML expression, a four-stage preclinical sequence is required, namely (1) suppression, (2) recovery, (3) accommodation, and (4) preleukemic transition. Within this pathological sequence, a critical early event has been identified as the acquisition of radioresistance by hematopoietic progenitors that serves to mediate a newfound regenerative hematopoietic capacity. As such, this event sets the stage'' for preleukemic progression by initiating progression from preclinical phase 1 to 2. Due to the nature of target cell suppression, the induction of crisis, and the outgrowth of progenitors with altered phenotypes, this preleukemic event resembles the immortalization'' step of the in vitro transformation sequence following induction with either physical and chemical carcinogens. The radiological, temporal, and biological dictates governing this event have been extensively evaluated and will be discussed in light of their role in the induction and progression of chronic radiation leukemia. 35 refs., 2 tabs.

  1. Refugees and Evacuees: Enhancing Historical Understanding through Irish Historical Fiction with Key Stage 2 and Early Key Stage 3 Pupils

    ERIC Educational Resources Information Center

    Bracey, Paul; Gove-Humphries, Alison; Jackson, Darius

    2006-01-01

    This article explores the use of historical fiction as a means of undertaking a historical enquiry into the experiences of refugees and evacuees with Key Stage 2 and 3 pupils. The authors reflect on the reasons why people have come to Britain before focussing on specific circumstances associated with World War 2. This is undertaken through the use…

  2. Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study

    SciTech Connect

    Cai Ling; Stauder, Michael C.; Zhang Yujing; Poortmans, Philip; Li Yexiong; Constantinou, Nicolaos; Thariat, Juliette; Kadish, Sidney P.; Nguyen, Tan Dat; Kirova, Youlia M.; Ghadjar, Pirus; Weber, Damien C.; Bertran, Victoria Tuset; Ozsahin, Mahmut; Mirimanoff, Rene-Olivier

    2012-05-01

    Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score {<=}1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

  3. Nephelinite lavas at early stage of rift initiation (Hanang volcano, North Tanzanian Divergence)

    NASA Astrophysics Data System (ADS)

    Baudouin, Céline; Parat, Fleurice; Denis, Carole M. M.; Mangasini, Fredrik

    2016-07-01

    North Tanzanian Divergence is the first stage of continental break-up of East African Rift (<6 Ma) and is one of the most concentrated areas of carbonatite magmatism on Earth, with singular Oldoinyo Lengai and Kerimasi volcanoes. Hanang volcano is the southernmost volcano in the North Tanzanian Divergence and the earliest stage of rift initiation. Hanang volcano erupted silica-undersaturated alkaline lavas with zoned clinopyroxene, nepheline, andradite-schorlomite, titanite, apatite, and pyrrhotite. Lavas are low MgO-nephelinite with low Mg# and high silica content (Mg# = 22.4-35.2, SiO2 = 44.2-46.7 wt%, respectively), high incompatible element concentrations (e.g. REE, Ba, Sr) and display Nb-Ta fractionation (Nb/Ta = 36-61). Major elements of whole rock are consistent with magmatic differentiation by fractional crystallization from a parental melt with melilititic composition. Although fractional crystallization occurred at 9-12 km and can be considered as an important process leading to nephelinite magma, the complex zonation of cpx (e.g. abrupt change of Mg#, Nb/Ta, and H2O) and trace element patterns of nephelinites recorded magmatic differentiation involving open system with carbonate-silicate immiscibility and primary melilititic melt replenishment. The low water content of clinopyroxene (3-25 ppm wt. H2O) indicates that at least 0.3 wt% H2O was present at depth during carbonate-rich nephelinite crystallization at 340-640 MPa and 1050-1100 °C. Mg-poor nephelinites from Hanang represent an early stage of the evolution path towards carbonatitic magmatism as observed in Oldoinyo Lengai. Paragenesis and geochemistry of Hanang nephelinites require the presence of CO2-rich melilititic liquid in the southern part of North Tanzanian Divergence and carbonate-rich melt percolations after deep partial melting of CO2-rich oxidized mantle source.

  4. Biogeochemical Changes at Early Stage After the Closure of Radioactive Waste Geological Repository in South Korea

    SciTech Connect

    Choung, Sungwook; Um, Wooyong; Choi, Seho; Francis, Arokiasamy J.; Kim, Sungpyo; Park, Jin beak; Kim, Suk-Hoon

    2014-09-01

    Permanent disposal of low- and intermediate-level radioactive wastes in the subterranean environment has been the preferred method of many countries, including Korea. A safety issue after the closure of a geological repository is that biodegradation of organic materials due to microbial activities generates gases that lead to overpressure of the waste containers in the repository and its disintegration with the release of radionuclides. As part of an ongoing large-scale in situ experiment using organic wastes and groundwater to simulate geological radioactive waste repository conditions, we investigated the geochemical alteration and microbial activities at an early stage (~63 days) intended to be representative of the initial period after repository closure. The increased numbers of both aerobes and facultative anaerobes in waste effluents indicate that oxygen content could be the most significant parameter to control biogeochemical conditions at very early periods of reaction (<35 days). Accordingly, the values of dissolved oxygen and redox potential were decreased. The activation of anaerobes after 35 days was supported by the increased concentration to ~50 mg L-1 of ethanol. These results suggest that the biogeochemical conditions were rapidly altered to more reducing and anaerobic conditions within the initial 2 months after repository closure. Although no gases were detected during the study, activated anaerobic microbes will play more important role in gas generation over the long term.

  5. Effects of Mixture of Pharmaceuticals on Early Life Stages of Tench (Tinca tinca)

    PubMed Central

    Stancova, Vlasta; Plhalova, Lucie; Bartoskova, Marta; Zivna, Dana; Prokes, Miroslav; Marsalek, Petr; Blahova, Jana; Skoric, Misa; Svobodova, Zdenka

    2014-01-01

    Ubiquitous occurrence of pharmaceuticals in aquatic environment results in concern about potential adverse the effects on nontarget organisms. In water, drugs are present in complex mixtures, in which complicated interactions affect toxicity of single components. The purpose of this study was to examine effect of 35-day-long exposure to mixture of ibuprofen, diclofenac, and carbamazepine on the mortality, growth, early ontogeny, and histopathological changes in tench (Tinca tinca). Early life stage toxicity test was carried out using a modified protocol according to OECD guideline 210. Exposure to mixture of pharmaceuticals at concentration of 60 μg·L−1 for each substance was associated with significant increase in mortality, as well as significant increase in growth and elevated incidence of malformations. Any of the tested concentrations resulted in histopathological changes of liver, kidney, skin, or gill. After fourteen days of exposure there was short-term delay of development related to increased concentrations of pharmaceuticals in the mixture (2, 20, and 60 μg·L−1). Environmentally relevant concentrations (0.02; and 0.2 μg·L−1) used in this experiment did not result in toxic impairment of tench. PMID:24772417

  6. A Report On Eight Early-Stage State And Regional Projects Testing Value-Based Payment

    PubMed Central

    Conrad, Douglas; Grembowski, David; Gibbons, Claire; Marcus-Smith, Miriam; Hernandez, Susan E.; Chang, Judy; Renz, Anne; Lau, Bernard; Cruz, Erin dela

    2014-01-01

    To help contain health care spending and improve the quality of care, practitioners and policy makers are trying to move away from fee-for-service toward value-based payment, which links providers’ reimbursement to the value, rather than the volume, of services delivered. With funding from the Robert Wood Johnson Foundation, eight grantees across the country are designing and implementing value-based payment reform projects. For example, in Salem, Oregon, the Physicians Choice Foundation is testing “Program Oriented Payments,” which include incentives for providers who follow a condition-specific program of care designed to meet goals set jointly by patient and provider. In this article we describe the funding rationale and the specific objectives, strategies, progress, and early stages of implementation of the eight projects. We also share some early lessons and identify prerequisites for success, such as ensuring that providers have broad and timely access to data so they can meet patients’ needs in cost-effective ways. PMID:23650332

  7. Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

    PubMed Central

    König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.

    2008-01-01

    Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154

  8. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia

    PubMed Central

    Pearson, John; Aitchison, Alan; Dixon, Liane; Frizelle, Frank A.; Keenan, Jacqueline I.

    2017-01-01

    Background Enterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum. Methods Mucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed. Findings We found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from the right side of the colon. Conclusion Our results showing association of ETBF positivity and increased abundance with early-stage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis. PMID:28151975

  9. Small pelagics in a changing ocean: biological responses of sardine early stages to warming

    PubMed Central

    Faleiro, Filipa; Pimentel, Marta; Pegado, Maria Rita; Bispo, Regina; Lopes, Ana Rita; Diniz, Mário S.; Rosa, Rui

    2016-01-01

    Small pelagic fishes are known to respond rapidly to changes in ocean climate. In this study, we evaluate the effects of future environmental warming (+2°C) during the early ontogeny of the European sardine, Sardina pilchardus. Warming reduced the survival of 30-day-old larvae by half. Length at hatching increased with temperature as expected, but no significant effect was observed on the length and growth at 30 days post-hatching. Warming did not significantly affect the thermal tolerance of sardine larvae, even though the mean lethal temperature increased by 1°C. In the warm conditions, sardine larvae showed signs of thermal stress, indicated by a pronounced increase in larval metabolism (Q10 = 7.9) and a 45% increase in the heat shock response. Lipid peroxidation was not significantly affected by the higher temperature, even though the mean value doubled. Warming did not affect the time larvae spent swimming, but decreased by 36% the frequency of prey attacks. Given the key role of these small pelagics in the trophic dynamics off the Western Iberian upwelling ecosystem, the negative effects of warming on the early stages may have important implications for fish recruitment and ecosystem structure. PMID:27293764

  10. Analysis of corneal morphologic and pathologic changes in early-stage congenital aniridic keratopathy

    PubMed Central

    Du, Juan; Liu, Rong-Qiang; Ye, Lei; Li, Zhi-Hui; Zhao, Feng-Tu; Jiang, Nan; Ye, Lin-Hong; Shao, Yi

    2017-01-01

    AIM To determine typical corneal changes of congenital aniridic keratopathy (CAK) using corneal topography and confocal systems, and to identify characteristics that might assist in early diagnosis. METHODS Patients with CAK and healthy control subjects underwent detailed ophthalmic examinations including axial length, corneal thickness, tear film condition, corneal topography, and laser-scanning in vivo confocal microscopy (IVCM). RESULTS In early stage aniridic keratopathy, Schirmer I test (SIT), break-up time (BUT), mean keratometry (mean K) and simulated keratometry (sim K) were reduced relative to controls (P<0.05), while simulation of corneal astigmatism (sim A) and corneal thickness were increased (P<0.05). In addition, significantly more eyes exhibited flat cornea compared with the control group. Inflammatory dendritic cells were present in the aniridic epithelium, with significantly increased density relative to controls (P<0.05). Palisade ridge-like features and abnormal cell morphology were observed in six out of sixteen CAK cases. In central cornea area, the aniridic corneas had the increased subbasal nerve density. CONCLUSION These changes in corneal morphology in borderline situations can be useful to confirm the diagnosis of CAK. PMID:28393028

  11. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

    PubMed

    Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

    2016-04-12

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  12. Is IL-33 useful to detect early stage of renal failure?

    PubMed

    Caner, Sedat; Usluoğulları, Celil Alper; Balkan, Fevzi; Büyükcam, Fatih; Kaya, Cafer; Saçıkara, Muhammed; Koca, Cemile; Ersoy, Reyhan; Çakır, Bekir

    2014-02-01

    IL-33 is a proinflammatory cytokine that is a member of IL-1 family. Previously the effect of IL-33 on kidney injury is showed in animal models. In this study, we searched if we can use IL-33 to show the early stage of kidney injury in diabetic patients. Three groups are identified: 26 patients in Group 1: Healthy group, that do not have any chronic diseases and not taking any medication; 42 patients in Group 2: DM (diabetes mellitus) group without any known kidney disease and with normal kidney functions; 32 patients in Group 3: DM + MA (microalbuminuria) group that are assumed to have nephropathy. IL-33 level of DM patient group is greater than healthy group; also IL-33 level of DM + MA patient group is greater than healthy group; but there is not any difference between DM and DM + MA group. The increase in IL-33 levels in diabetic nephropathy is not associated with kidney injury but the increase could be resulting because of diabetes. So IL-33 cannot be used in early recognition of diabetic nephropathy.

  13. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    PubMed Central

    Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

    2016-01-01

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

  14. The ReSTAGE Collaboration: Defining Optimal Bleeding Criteria for Onset of Early Menopausal Transition

    PubMed Central

    Harlow, Siobán D.; Mitchell, Ellen S.; Crawford, Sybil; Nan, Bin; Little, Roderick; Taffe, John

    2008-01-01

    Study objective Criteria for staging the menopausal transition are not established. This paper evaluates five bleeding criteria for defining early transition and provides empirically-based guidance regarding optimal criteria. Design/Setting Prospective menstrual calendar data from four population-based cohorts: TREMIN, Melbourne Women’s Midlife Health Project(MWMHP), Seattle Midlife Women’s Health Study(SMWHS), and Study of Women’s Health Across the Nation(SWAN) with annual serum follicle stimulating hormone (FSH) from MWMHP and SWAN. Participants 735 TREMIN, 279 SMWHS, 216 MWMHP, and 2270 SWAN women aged 35-57 at baseline who maintained menstrual calendars. Main outcome measure(s) Age at and time to menopause for: standard deviation >6 and >8 days, persistent difference in consecutive segments >6 days, irregularity, and >=45 day segment. Serum follicle stimulating hormone concentration. Results Most women experienced each of the bleeding criteria. Except for persistent >6 day difference which occurs earlier, the criteria occur at a similar age and at approximately the same age as late transition in a large proportion of women. FSH was associated with all proposed markers. Conclusions The early transition may be best described by ovarian activity consistent with the persistent >6 day difference, but further study is needed, as other proposed criterion are consistent with later menstrual changes. PMID:17681300

  15. Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

    PubMed Central

    Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

    2014-01-01

    Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m2, and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

  16. Phytoplankton dynamics in contrasting early stage North Atlantic spring blooms: composition, succession, and potential drivers

    NASA Astrophysics Data System (ADS)

    Daniels, C. J.; Poulton, A. J.; Esposito, M.; Paulsen, M. L.; Bellerby, R.; St John, M.; Martin, A. P.

    2015-04-01

    The spring bloom is a key annual event in the phenology of pelagic ecosystems, making a major contribution to the oceanic biological carbon pump through the production and export of organic carbon. However, there is little consensus as to the main drivers of spring bloom formation, exacerbated by a lack of in situ observations of the phytoplankton community composition and its evolution during this critical period. We investigated the dynamics of the phytoplankton community structure at two contrasting sites in the Iceland and Norwegian basins during the early stage (25 March-25 April) of the 2012 North Atlantic spring bloom. The plankton composition and characteristics of the initial stages of the bloom were markedly different between the two basins. The Iceland Basin (ICB) appeared well mixed down to >400 m, yet surface chlorophyll a (0.27-2.2 mg m-3) and primary production (0.06-0.66 mmol C m-3 d-1) were elevated in the upper 100 m. Although the Norwegian Basin (NWB) had a persistently shallower mixed layer (<100 m), chlorophyll a (0.58-0.93 mg m-3) and primary production (0.08-0.15 mmol C m-3 d-1) remained lower than in the ICB, with picoplankton (<2 μm) dominating chlorophyll a biomass. The ICB phytoplankton composition appeared primarily driven by the physicochemical environment, with periodic events of increased mixing restricting further increases in biomass. In contrast, the NWB phytoplankton community was potentially limited by physicochemical and/or biological factors such as grazing. Diatoms dominated the ICB, with the genus Chaetoceros (1-166 cells mL-1) being succeeded by Pseudo-nitzschia (0.2-210 cells mL-1). However, large diatoms (>10 μm) were virtually absent (<0.5 cells mL-1) from the NWB, with only small nano-sized (<5 μm) diatoms (i.e. Minidiscus spp.) present (101-600 cells mL-1). We suggest microzooplankton grazing, potentially coupled with the lack of a seed population of bloom-forming diatoms, was restricting diatom growth in the NWB

  17. Phytoplankton dynamics in contrasting early stage North Atlantic spring blooms: composition, succession, and potential drivers

    NASA Astrophysics Data System (ADS)

    Daniels, C. J.; Poulton, A. J.; Esposito, M.; Paulsen, M. L.; Bellerby, R.; St. John, M.; Martin, A. P.

    2015-01-01

    The spring bloom is a key annual event in the phenology of pelagic ecosystems, making a major contribution to the oceanic biological carbon pump through the production and export of organic carbon. However, there is little consensus as to the main drivers of spring bloom formation, exacerbated by a lack of in situ observations of the phytoplankton community composition and its evolution during this critical period. We investigated the dynamics of the phytoplankton community structure at two contrasting sites in the Iceland and Norwegian Basins during the early stage (25 March-25 April) of the 2012 North Atlantic spring bloom. The plankton composition and characteristics of the initial stages of the bloom were markedly different between the two basins. The Iceland Basin (ICB) appeared well mixed to > 400 m, yet surface chlorophyll a (0.27-2.2 mg m-3) and primary production (0.06-0.66 mmol C m-3 d-1) were elevated in the upper 100 m. Although the Norwegian Basin (NWB) had a persistently shallower mixed layer (< 100 m), chlorophyll a (0.58-0.93 mg m-3) and primary production (0.08-0.15 mmol C m-3 d-1) remained lower than in the ICB, with picoplankton (> 2 μm) dominating chlorophyll a biomass. The ICB phytoplankton composition appeared primarily driven by the physicochemical environment, with periodic events of increased mixing restricting further increases in biomass. In contrast, the NWB phytoplankton community was potentially limited by physicochemical and/or biological factors such as grazing. Diatoms dominated the ICB, with the genus Chaetoceros (1-166 cells mL-1) being succeeded by Pseudo-nitzschia (0.2-210 cells mL-1). However, large diatoms (> 10 μm) were virtually absent (< 0.5 cells mL-1) from the NWB, with only small nanno-sized (< 5 μm) diatoms present (101-600 cells mL-1). We suggest micro-zooplankton grazing, potentially coupled with the lack of a seed population of bloom forming diatoms, was restricting diatom growth in the NWB, and that large diatoms

  18. Public–private partnerships improve health outcomes in individuals with early stage Alzheimer’s disease

    PubMed Central

    Galvin, James E; Tolea, Magdalena I; George, Nika; Wingbermuehle, Cheryl

    2014-01-01

    Purpose In a collaborative effort between the Missouri Department of Health, Area Agencies on Aging (AAA), Alzheimer Association, and academic researchers, we tested whether early dementia detection and comprehensive care consultations would improve health outcomes in care receivers (CRs) and their family caregivers (FCGs), therefore addressing an important public health concern. Participants and methods A total of 244 community-dwelling older adults screened for early-stage dementia by the AAA field staff were referred to the Alzheimer Association and participated in Project Learn MORE (Missouri Outreach and Referral Expanded) (PLM) – a 2-year, nonrandomized multisite intervention consisting of comprehensive care consultations to improve coping skills. PLM participants were compared against 96 controls receiving the Alzheimer Association’s “usual services” between January 2011 and December 2012. We examined CR and FCG outcomes, including burden, care confidence, and mood, as effects of PLM, on delaying transitions in level of care. Results CRs showed improved knowledge (P=0.002) and reduced depression (P=0.007), while FCGs demonstrated improved knowledge (P=0.003) and ability to identify sources of support for the CR (P=0.032) and for themselves (P=0.043). However, FCGs were more burdened after PLM (P=0.02), due to increased awareness of Alzheimer’s disease. PLM delayed transitions in care (odds ratio [OR] 3.32, 95% confidence level [CI]: 1.25–8.83) with the number needed to treat =6.82. Conclusion PLM was successful in improving detection of incident cases of dementia in the community and in connecting patients and their families with needed services. Our findings support the use of state agencies and community service partners to detect dementia. Early implementation of psychosocial interventions could have significant impact in improving patient- and family-centered outcomes, potentially providing a cost-efficient alternative to pharmacotherapy

  19. Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine

    PubMed Central

    2016-01-01

    Abstract Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved “upstream” so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bridges between oral health and systems medicine since what happens in oral health affects systems pathophysiology, and vice versa. This article offers a synthesis of the latest trends and approaches in early phase HTA, with a view to near future applications in oral health, systems medicine, and biomarker-guided precision medicine. In brief, this review underscores that demonstrating health outcomes of biomarkers and next-generation diagnostics is particularly challenging because they do not always influence long-term outcomes directly, but rather impact subsequent care processes. Biomarker testing costs are typically less of a barrier to uptake in practice than the biomarker's impact on longer term health outcomes. As a single biomarker or next-generation diagnostic in oral health can inform decisions about numerous downstream diagnosis-treatment combinations, early stage “upstream” HTA is crucial in prioritizing the most valuable diagnostic applications to pursue first. For the vast array of oral health biomarkers currently developed, early HTA is necessary to timely and iteratively assess their comparative effectiveness and anticipate the inevitable questions about value for money from regulators and payers. PMID:26760958

  20. Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine.

    PubMed

    Steuten, Lotte M G

    2016-01-01

    Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved "upstream" so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bridges between oral health and systems medicine since what happens in oral health affects systems pathophysiology, and vice versa. This article offers a synthesis of the latest trends and approaches in early phase HTA, with a view to near future applications in oral health, systems medicine, and biomarker-guided precision medicine. In brief, this review underscores that demonstrating health outcomes of biomarkers and next-generation diagnostics is particularly challenging because they do not always influence long-term outcomes directly, but rather impact subsequent care processes. Biomarker testing costs are typically less of a barrier to uptake in practice than the biomarker's impact on longer term health outcomes. As a single biomarker or next-generation diagnostic in oral health can inform decisions about numerous downstream diagnosis-treatment combinations, early stage "upstream" HTA is crucial in prioritizing the most valuable diagnostic applications to pursue first. For the vast array of oral health biomarkers currently developed, early HTA is necessary to timely and iteratively assess their comparative effectiveness and anticipate the inevitable questions about value for money from regulators and payers.

  1. Computer Simulation on the Cooperation of Functional Molecules during the Early Stages of Evolution

    PubMed Central

    Ma, Wentao; Hu, Jiming

    2012-01-01

    It is very likely that life began with some RNA (or RNA-like) molecules, self-replicating by base-pairing and exhibiting enzyme-like functions that favored the self-replication. Different functional molecules may have emerged by favoring their own self-replication at different aspects. Then, a direct route towards complexity/efficiency may have been through the coexistence/cooperation of these molecules. However, the likelihood of this route remains quite unclear, especially because the molecules would be competing for limited common resources. By computer simulation using a Monte-Carlo model (with “micro-resolution” at the level of nucleotides and membrane components), we show that the coexistence/cooperation of these molecules can occur naturally, both in a naked form and in a protocell form. The results of the computer simulation also lead to quite a few deductions concerning the environment and history in the scenario. First, a naked stage (with functional molecules catalyzing template-replication and metabolism) may have occurred early in evolution but required high concentration and limited dispersal of the system (e.g., on some mineral surface); the emergence of protocells enabled a “habitat-shift” into bulk water. Second, the protocell stage started with a substage of “pseudo-protocells”, with functional molecules catalyzing template-replication and metabolism, but still missing the function involved in the synthesis of membrane components, the emergence of which would lead to a subsequent “true-protocell” substage. Third, the initial unstable membrane, composed of prebiotically available fatty acids, should have been superseded quite early by a more stable membrane (e.g., composed of phospholipids, like modern cells). Additionally, the membrane-takeover probably occurred at the transition of the two substages of the protocells. The scenario described in the present study should correspond to an episode in early evolution, after the

  2. Is surgery indicated for elderly patients with early stage nonsmall cell lung cancer, in the era of stereotactic body radiotherapy?

    PubMed Central

    Nguyen, Nam P.; Godinez, Juan; Shen, Wei; Vinh-Hung, Vincent; Gorobets, Helena; Thariat, Juliette; Ampil, Fred; Vock, Jacqueline; Karlsson, Ulf; Chi, Alexander

    2016-01-01

    Abstract Background: The aim of this article is to assess the influence of comorbidities among elderly patients (at least 70 year old) undergoing surgery for early stage nonsmall cell lung cancer (NSCLC) and to explore the tolerability and efficacy of surgery in relation to stereotactic body radiotherapy (SBRT) in this patient population. Methods: A review of the literature on the prevalence of comorbidities among elderly patients with early stage NSCLC, and the impact of comorbidity factors on survival following surgery was conducted. Survival rates and the incidence of complications following SBRT for this patient population were also identified. Results: Comorbidities in elderly patients with early stage NSCLC may preclude surgery or lead to poor survival following surgery. However, chronological age alone should not be used as a deciding factor to deny curative treatment in elderly, but fit patients. Stereotactic body radiotherapy is well tolerated by elderly lung cancer patients and may result in survival rates similar to that following surgery. Conclusion: SBRT should be the treatment of choice for early stage NSCLC in elderly patients with multiple comorbidities that preclude surgery. The roles of surgery and SBRT for elderly, -fit patients with early stage NSCLC needs to be further defined in future prospective trials. PMID:27787380

  3. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    PubMed Central

    Niu, Chunhao; Sun, Xiaoying; Zhang, Weijing; Li, Han; Xu, Liqun; Li, Jun; Xu, Benke; Zhang, Yanna

    2016-01-01

    Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer. PMID:27775588

  4. Comprehensive out-patient pulmonary rehabilitation: Treatment outcomes in early and late stages of chronic obstructive pulmonary disease

    PubMed Central

    Ergün, Pinar; Kaymaz, Dicle; Günay, Ersin; Erdoğan, Yurdanur; Turay, Ülkü Yilmaz; Demir, Neşe; Çanak, Ebru; Sengül, Fatma; Egesel, Nurcan; Köse, Serdal Kenan

    2011-01-01

    BACKGROUND: The aim was to evaluate the outcomes of a comprehensive pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) and to establish whether in early disease stage PR is as effective as in late stages of disease. METHODS: A total of 55 stable COPD patients, 28 with early and 27 with late disease stages, were assessed. Patients underwent a comprehensive out-patient PR program for 8 weeks. To eluciate the effects of PR and compare the level of improvement; lung function, dyspnea sensation [Medical Research Council (MRC)], body composition [body mass index (BMI), fat free mass (FFM), fat free mass index (FFMI)], exercise capacity [incremental shuttle walking test, endurance shuttle walking test], health related quality of life (HRQoL) with St. George Respiratory Disease Questionnaire, psycohological status (Hospital anxiety–depression (HAD) scale) were evaluated before and after PR. RESULTS: At the end of PR in the early disease stage group, the improvement in forced vital capacity (FVC) reached a statistically significant level (P < 0.05). In both disease stages, there were no significant differences in BMI, FFM, and FFMI. The decrease in exertional dyspnea for the two groups evaluated with the modified BORG scale were not found statistically significant, though the dyspnea scores evaluated with MRC showed significant improvements (P < 0.001). HRQoL and exercise capacity were significantly improved for the two groups (P < 0.001). Psychological status evaluated with the HAD scale improved after PR (P < 0.001) both in early and late stages. Gainings in the study parameters did not differ in the early and the late disease stages. CONCLUSIONS: These results showed that patients with COPD had benefited from a comprehensive PR program in an out-patient setting regardless of disease severity. Even patients with earlier stage of disease should be referred and encouraged to participate in a PR program. PMID:21572695

  5. Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

    PubMed Central

    Malone, James P.; Shah, Aarti R.; Gilmore, Petra; Davis, Alan E.; Roe, Catherine M.; Peskind, Elaine R.; Li, Ge; Galasko, Douglas R.; Clark, Christopher M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Morris, John C.; Holtzman, David M.; Townsend, R. Reid; Fagan, Anne M.

    2011-01-01

    Background Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the ‘preclinical’ stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome. Methods and Findings CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85–0.94 95% confidence interval [CI]) and 0.88 (0.81–0.94 CI), respectively. Conclusions Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel

  6. Different effects of ERβ and TROP2 expression in Chinese patients with early-stage colon cancer.

    PubMed

    Fang, Yu-Jing; Wang, Guo-Qiang; Lu, Zhen-Hai; Zhang, Lin; Li, Ji-Bin; Wu, Xiao-Jun; Ding, Pei-Rong; Ou, Qing-Jian; Zhang, Mei-Fang; Jiang, Wu; Pan, Zhi-Zhong; Wan, De-Sen

    2012-12-01

    Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

  7. [The ultrasonography of the capsular ligamentous apparatus of the knee joint in the early stages of rheumatoid arthritis].

    PubMed

    Herasymenko, S I; Huzhevs'kyĭ, I V; Vovchenko, H Ia; Babko, A N

    1999-07-01

    With the purpose of finding out informative value of the ultrasound investigation designed to study the capsular and ligamentous apparatus of the knee joint in its instability during the early stages of rheumatoid arthritis and correlating clinical symptoms with ultrasonographic findings an examination was done of twenty joints of patients in early stages of rheumatoid arthritis presenting with clinical signs of anterior-medial instability. Sonography confirmed the presence of instability and permitted the qualitative assessment of its degree to be done. The method allows us to disclose relative incompetence of the anterior-medial sector of the knee joint in those patients presenting with early stages of rheumatoid arthritis, which is one of causes of instability, with the cruciate and lateral ligaments remaining uninjured. Ultrasonography makes it possible to perform a quantitative assessment of the degree of instability of the joint irrespective of the clinical test used and experience of the orthopedist.

  8. Cumulative Effects of Nutrient Enrichment and Elevated Temperature Compromise the Early Life History Stages of the Coral Acropora tenuis

    PubMed Central

    Noonan, Sam H. C.; Willis, Bette L.; Fabricius, Katharina E.; Negri, Andrew P.

    2016-01-01

    Inshore coral reefs are experiencing the combined pressures of excess nutrient availability associated with coastal activities and warming seawater temperatures. Both pressures are known to have detrimental effects on the early life history stages of hard corals, but studies of their combined effects on early demographic stages are lacking. We conducted a series of experiments to test the combined effects of nutrient enrichment (three levels) and elevated seawater temperature (up to five levels) on early life history stages of the inshore coral Acropora tenuis, a common species in the Indo-Pacific and Red Sea. Gamete fertilization, larval survivorship and larval settlement were all significantly reduced as temperature increased, but only fertilization was further affected by simultaneous nutrient enrichment. Combined high temperatures and nutrient enrichment affected fertilization in an additive manner, whereas embryo abnormalities increased synergistically. Higher than normal temperatures (32°C) increased coral juvenile growth rates 1.6-fold, but mortality also increased by 50%. The co-occurrence of nutrient enrichment with high temperatures reduced juvenile mortality to 36%, ameliorating temperature stress (antagonistic interaction). Overall, the types of effect (additive vs synergistic or antagonistic) and their magnitude varied among life stages. Gamete and embryo stages were more affected by temperature stress and, in some cases, also by nutrient enrichment than juveniles. The data suggest that coastal runoff events might exacerbate the impacts of warming temperatures on fertilization if these events co-occur during corals spawning. The cumulative impacts of simultaneous exposure to nutrient enrichment and elevated temperatures over all early life history stages increases the likelihood for failure of larval supply and recruitment for this coral species. Our results suggest that improving the water quality of river discharges into coastal areas might help to

  9. Comparative toxicity of inorganic contaminants released by placer mining to early life stages of salmonids

    SciTech Connect

    Buhl, K.J.; Hamilton, S.J. )

    1990-12-01

    The acute toxicities of four trace inorganics associated with placer mining were determined, individually and in environmentally relevant mixtures, to early life stages of Arctic grayling (Thymallus arcticus) from Alaska and Montana, coho salmon (Oncorhynchus kisutch) from Alaska and Washington, and rainbow trout (Oncorhynchus mykiss) from Montana. The descending rank order of toxicity to all species and life stages was copper greater than zinc greater than lead greater than arsenic. For each of the three species, sensitivity to the inorganics was greater in juveniles than in alevins or in swim-up fry. Arctic grayling from Alaska were more sensitive than the other species tested, including Arctic grayling from Montana. For Arctic grayling, sensitivity to all four inorganics was significantly greater in swim-up fry from Alaska than in alevins from Montana, and sensitivity to arsenic and copper was significantly greater in juveniles from Alaska than in juveniles from Montana. In tests with environmentally relevant mixtures (based on ratios of concentrations measured in streams with placer mining) of these four inorganics, copper was identified as the major toxic component because it accounted for greater than or equal to 97% of the summed toxic units of the mixture, and an equitoxic mixture of these inorganics showed less-than-additive toxicity. Total and total recoverable copper concentrations reported in five Alaskan streams with active placer mines were higher than the acutely toxic concentrations that the authors found to be acutely toxic to Arctic grayling and coho salmon from Alaska. However, caution should be used when comparing our results obtained in 'clear' water to field situations, because speciation and toxicity of these inorganics may be altered in the presence of sediments suspended by placer mining activities.

  10. Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

    SciTech Connect

    Lemanski, Claire; Azria, David; Gourgon-Bourgade, Sophie; Gutowski, Marian; Rouanet, Phillippe; Saint-Aubert, Bernard; Ailleres, Norbert; Fenoglietto, Pascal; Dubois, Jean-Bernard

    2010-03-01

    Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

  11. Heat transfer and microstructure during the early stages of metal solidification

    NASA Astrophysics Data System (ADS)

    Muojekwu, C. A.; Samarasekera, I. V.; Brimacombe, J. K.

    1995-04-01

    Transient heat transfer in the early stages of solidification of an alloy on a water-cooled chill and the consequent evolution of microstructure, quantified in terms of secondary dendrite arm spacing (SDAS), have been studied. Based on dip tests of the chill, instrumented with thermocouples, into Al-Si alloys, the influence of process variables such as mold surface roughness, mold material, metal superheat, alloy composition, and lubricant on heat transfer and cast structure has been determined. The heat flux between the solidifying metal and substrate, computed from measurements of transient temperature in the chill by the inverse heat-transfer technique, ranged from low values of 0.3 to 0.4 MW/m2 to peak values of 0.95 to 2.0 MW/m2. A onedimensional, implicit, finite-difference model was applied to compute heat-transfer coefficients, which ranged from 0.45 to 4.0 kW/m2 °C, and local cooling rates of 10 °C/s to 100 °C/s near the chill surface, as well as growth of the solidifying shell. Near the chill surface, the SDAS varied from 12 to 22 ( µm while at 20 mm from the chill, values of up to 80 /smm were measured. Although the SDAS depended on the cooling rate and local solidification time, it was also found to be a direct function of the heat-transfer coefficient at distances very near to the casting/chill interface. A three-stage empirical heat-flux model based on the thermophysical properties of the mold and casting has been proposed for the simulation of the mold/casting boundary condition during solidification. The applicability of the various models proposed in the literature relating the SDAS to heat-transfer parameters has been evaluated and the extension of these models to continuous casting processes pursued.

  12. Prognosis for Mammographically Occult, Early-Stage Breast Cancer Patients Treated With Breast-Conservation Therapy

    SciTech Connect

    Yang, Tzu-I. J.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2010-01-15

    Purpose: To compare mammographically occult (MamOcc) and mammographically positive (MamPos) early-stage breast cancer patients treated with breast-conservation therapy (BCT), to analyze differences between the two cohorts. Methods and Materials: Our two cohorts consisted of 214 MamOcc and 2168 MamPos patients treated with BCT. Chart reviews were conducted to assess mammogram reports and method of detection. All clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. Results: Median follow-up was 7 years. There were no differences in final margins, T stage, nodal status, estrogen/progesterone receptor status, or 'triple-negative' status. Significant differences included younger age at diagnosis (p < 0.0001), more positive family history (p = 0.0033), less HER-2+ disease (p = 0.0294), and 1{sup o} histology (p < 0.0001). At 10 years, the differences in overall survival, cause-specific survival, and distant relapse between the two groups did not differ significantly. The MamOcc cohort had more breast relapses (15% vs. 8%; p = 0.0357), but on multivariate analysis this difference was not significant (hazard ratio 1.0, 95% confidence interval 0.993-1.007, p = 0.9296). Breast relapses were mammographically occult in 32% of the MamOcc and 12% of the MamPos cohorts (p = 0.0136). Conclusions: Although our study suggests that there are clinical-pathologic variations for the MamOcc cohort vs. MamPos patients that may ultimately affect management, breast relapse after BCT was not significantly different. Breast recurrences were more often mammographically occult in the MamOcc cohort; consideration should be given to closer follow-up and alternative imaging strategies (ultrasound, breast MRI) for routine posttreatment examination. To our knowledge, this represents the largest series addressing the prognostic significance of MamOcc cancers treated with BCT.

  13. Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

    PubMed Central

    Midgett, Madeline; López, Claudia S.; David, Larry; Maloyan, Alina; Rugonyi, Sandra

    2017-01-01

    Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease. However, the progressive detrimental remodeling processes that relate altered blood flow to cardiac defects remain unclear. Endothelial–mesenchymal cell transition is one of the many complex developmental events involved in transforming the early embryonic outflow tract into the aorta, pulmonary trunk, interventricular septum, and semilunar valves. This study elucidated the effects of increased hemodynamic load on endothelial–mesenchymal transition remodeling of the outflow tract cushions in vivo. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24. Increased hemodynamic load induced increased cell density in outflow tract cushions, fewer cells along the endocardial lining, endocardium junction disruption, and altered periostin expression as measured by confocal microscopy analysis. In addition, 3D focused ion beam scanning electron microscopy analysis determined that a portion of endocardial cells adopted a migratory shape after outflow tract banding that is more irregular, elongated, and with extensive cellular projections compared to normal cells. Proteomic mass-spectrometry analysis quantified altered protein composition after banding that is consistent with a more active stage of endothelial–mesenchymal transition. Outflow tract banding enhances the endothelial–mesenchymal transition phenotype during formation of the outflow tract cushions, suggesting that endothelial–mesenchymal transition is a critical developmental process that when disturbed by altered blood flow gives rise to cardiac malformation and defects. PMID:28228731

  14. Involved-Field, Low-Dose Chemoradiotherapy for Early-Stage Anal Carcinoma

    SciTech Connect

    Hatfield, Paul; Cooper, Rachel; Sebag-Montefiore, David

    2008-02-01

    Purpose: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. Methods and Materials: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m{sup 2} on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m{sup 2}/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that were excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. Results: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. Conclusion: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.

  15. Progression of gingival squamous cell carcinoma from early to late stage after invasive dental procedure.

    PubMed

    Hinchy, Nicole V; Jayaprakash, Vijayvel; Rigual, Nestor; Reid, Mary; Frustino, Jennifer L; Rossitto, Rachael; Groman, Adrienne; Sullivan, Maureen A

    2016-01-01

    Early presentation of gingival squamous cell carcinoma (GSCC) is at times misdiagnosed as a benign inflammatory or reactive oral condition. Some misdiagnosed patients undergo unnecessary, invasive dental procedures, resulting in delayed cancer diagnosis and an increased risk of accelerated disease progression due to disruption of the periosteum and cortical bone. The records of 58 patients with biopsy-proven GSCC were retrospectively reviewed. The sample included 32 patients who underwent an invasive dental procedure (IDP) prior to cancer diagnosis and 26 patients who did not undergo an IDP (non-case group). Patients from both groups initially presented with similar symptoms. The median duration of symptoms at initial clinical presentation was 6 months for the IDP group and 2 months for the non-case group. In IDP patients, symptoms worsened after the IDP was rendered, with 37.5% presenting with a severe-grade symptom. In both groups, the majority of lesions were found on the posterior mandible and had a histologic grading of moderately differentiated GSCC. The odds of the IDP group having late-stage disease were 2.94 times greater than the odds for the control group. Stage T3/T4 malignancy was diagnosed in 77.4% of the IDP patients versus 53.8% of non-case patients. Disease-specific mortality was comparable; however, surgical treatment was significantly more extensive in the IDP group than in the non-case group. The disruption of alveolar periosteum in undiagnosed oral cancer patients results in significant delay in diagnosis, necessitating more complicated treatment regimens because of local tumor progression.

  16. Evidence from neglect dyslexia for morphological decomposition at the early stages of orthographic-visual analysis

    PubMed Central

    Reznick, Julia; Friedmann, Naama

    2015-01-01

    This study examined whether and how the morphological structure of written words affects reading in word-based neglect dyslexia (neglexia), and what can be learned about morphological decomposition in reading from the effect of morphology on neglexia. The oral reading of 7 Hebrew-speaking participants with acquired neglexia at the word level—6 with left neglexia and 1 with right neglexia—was evaluated. The main finding was that the morphological role of the letters on the neglected side of the word affected neglect errors: When an affix appeared on the neglected side, it was neglected significantly more often than when the neglected side was part of the root; root letters on the neglected side were never omitted, whereas affixes were. Perceptual effects of length and final letter form were found for words with an affix on the neglected side, but not for words in which a root letter appeared in the neglected side. Semantic and lexical factors did not affect the participants' reading and error pattern, and neglect errors did not preserve the morpho-lexical characteristics of the target words. These findings indicate that an early morphological decomposition of words to their root and affixes occurs before access to the lexicon and to semantics, at the orthographic-visual analysis stage, and that the effects did not result from lexical feedback. The same effects of morphological structure on reading were manifested by the participants with left- and right-sided neglexia. Since neglexia is a deficit at the orthographic-visual analysis level, the effect of morphology on reading patterns in neglexia further supports that morphological decomposition occurs in the orthographic-visual analysis stage, prelexically, and that the search for the three letters of the root in Hebrew is a trigger for attention shift in neglexia. PMID:26528159

  17. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer.

    PubMed

    Heegaard, Niels H H; Schetter, Aaron J; Welsh, Judith A; Yoneda, Mitsuhiro; Bowman, Elise D; Harris, Curtis C

    2012-03-15

    Circulating micro-RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro-RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT-PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro-RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a were significantly reduced in the serum of NSCLC cases, while miR-29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let-7b was modestly associated with worse cancer-specific mortality in all patients, and reduced serum expression of miR-223 was modestly associated with cancer-specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let-7b is associated with prognosis in NSCLC.

  18. Blue-Black or White-Gold? Early Stage Processing and the Color of 'The Dress'

    PubMed Central

    Rabin, Jeff

    2016-01-01

    Purpose In Feb 2015 an image of a dress posted on Tumblr triggered an internet phenomenon: Is the Dress blue and black (BB) or white and gold (WG)? Many claim BB and others insist WG while the true colors are BB. The prevailing theory is that assumptions about the illuminant govern perception of the Dress with WG due to bluish lighting and BB due to yellowish. Our purpose was to determine if early stage optical, retinal and/or neural factors also impact perception of the Dress. Methods Thirty-nine subjects were categorized as BB or WG based on their initial perception of the Dress and their perception reported when viewing the Dress on iPhone 5, iPad, and 22” LCD displays. Macular pigment optical density (MPOD) measured with the QuantifEye™ MPS II and visual brainwaves (VEPs) in response to brief presentations of a transparency of the Dress illuminated by a flashing light were measured on each subject and compared between BB and WG groups. Additionally, CIE chromaticity (color) and luminance (brightness) were measured from multiple areas of the Dress image to determine cone stimulation and contrast. Results Mean MPOD was higher in the WG group (0.49) vs. the BB (0.41, p = 0.04) and median values were higher as well (WG = 0.46, BB = 0.36, p = 0.03). There was no difference in VEP amplitude between groups (p > 0.85) but mean VEP latency was longer in WG (130 msec.) vs. the BB group (107 msec., p = 0.0005). Colorimetry of the Dress showed significantly greater stimulation of blue cones (contrast = 73%) vs. red and green sensitive cones (contrast = 13%). Conclusions Our findings indicate that observers with denser MPOD may be predisposed to perceive the Dress as WG due to great absorption of blue light by the macular pigment. Moreover, the novel, substantial stimulation of blue cones by the Dress may contribute to ambiguity and dichotomous perception since the blue cones are so sparse in the retina. Finally, the delayed WG VEPs indicate distinct neural processing

  19. Application of molecular endpoints in early life stage salmonid environmental biomonitoring.

    PubMed

    Marlatt, Vicki L; Sherrard, Ryan; Kennedy, Chris J; Elphick, James R; Martyniuk, Christopher J

    2016-04-01

    Molecular endpoints can enhance existing whole animal bioassays by more fully characterizing the biological impacts of aquatic pollutants. Laboratory and field studies were used to examine the utility of adopting molecular endpoints for a well-developed in situ early life stage (eyed embryo to onset of swim-up fry) salmonid bioassay to improve diagnostic assessments of water quality in the field. Coastal cutthroat trout (Oncorhynchus clarki clarki) were exposed in the laboratory to the model metal (zinc, 40μg/L) and the polycyclic aromatic hydrocarbon (pyrene, 100μg/L) in water to examine the resulting early life stage salmonid responses. In situ field exposures and bioassays were conducted in parallel to evaluate the water quality of three urban streams in British Columbia (two sites with anthropogenic inputs and one reference site). The endpoints measured in swim-up fry included survival, deformities, growth (weight and length), vitellogenin (vtg) and metallothionein (Mt) protein levels, and hepatic gene expression (e.g., metallothioneins [mta and mtb], endocrine biomarkers [vtg and estrogen receptors, esr] and xenobiotic-metabolizing enzymes [cytochrome P450 1A3, cyp1a3 and glutathione transferases, gstk]). No effects were observed in the zinc treatment, however exposure of swim-up fry to pyrene resulted in decreased survival, deformities and increased estrogen receptor alpha (er1) mRNA levels. In the field exposures, xenobiotic-metabolizing enzymes (cyp1a3, gstk) and zinc transporter (zntBigM103) mRNA were significantly increased in swim-up fry deployed at the sites with more anthropogenic inputs compared to the reference site. Cluster analysis revealed that gene expression profiles in individuals from the streams receiving anthropogenic inputs were more similar to each other than to the reference site. Collectively, the results obtained in this study suggest that molecular endpoints may be useful, and potentially more sensitive, indicators of site

  20. Early life-stage mortalities of Japanese medaka (Oryzias latipes) exposed to polychlorinated diphenyl ethers

    SciTech Connect

    Metcalfe, C.D.; Metcalfe, T.L.; Cormier, J.A.; Huestis, S.Y.; Niimi, A.J.

    1997-08-01

    Polychlorinated diphenyl ethers (PCDEs) are a group of compounds that resemble polychlorinated dibenzofurans in structure that have been detected at ppb concentrations in fish from the Great Lakes. The objective of this project was to determine the toxicological significance of PCDE residues in fish. PCDE congener 77 (3,3{prime},4,4{prime}-tetrachlorodiphenyl ether), congener 71 (2,3{prime},4{prime},6-tetrachlorodiphenyl ether), congener 118 (2,3{prime}4,4{prime},5-pentachlorodiphenyl ether), and congener 105 (2,3,3{prime},4,4{prime}-pentachlorodiphenyl) were tested for toxicity with early life stages (ELS) of Japanese medaka, Oryzias latipes. These embryotoxicity data showed that the mono-ortho congeners 105 and 118 and the non-ortho congener 77 were embryotoxic to medaka. However, the toxic equivalency factors (TEFs) estimated for congeners 105, 77, and 118 relative to 2,3,7,8-TCDD were relatively low at 0.00056, 0.00003, and 0.00001, respectively. PCDE compounds were isolated in a fraction prepared from a bulk extract of Lake Ontario lake trout. In this fraction, congeners 99 (2,2{prime},4,4{prime},5-pentaCDE), 153 (2,2{prime},4,m4{prime},5,5{prime}-hexaCDE), 154 (2,2{prime},4,4{prime},5,6{prime}-hexaCDE), and 163 (2,3,3{prime},4{prime},5,6-hexaCDE) comprised 81.3% of total PCDEs, while congeners 77, 71, 118, and 105 comprised only 1.1% of total PCDEs. The LC50 for embryotoxicity of this fraction was equivalent to 15.5 ng/ml of total PCDEs. Toxicopathic lesions noted in medaka embryos exposed to either individual PCDEs or the lake trout extract included vascular hemorrhage but no edematous lesions. Medaka fry did not exhibit symptoms of hyperexcitability prior to death, as has been noted for ELS of lake trout exhibiting swim-up syndrome. These data indicate that PCDEs in Lake Ontario lake trout have the potential to induce toxic effects in early life stages of fish.

  1. Observations of Nucleation and Early Stage Growth of Amorphous Silica on Carboxyl-Terminated Model Biosubstrates

    NASA Astrophysics Data System (ADS)

    Wallace, A. F.; Dove, P. M.

    2005-12-01

    surface. While controlling solution chemistry, we can make in situ measurements of nucleation and early stage growth at these interfaces with Atomic Force Microscopy (AFM). Preliminary experiments show that at pH 4 to 7, and supersaturations of 0.76 to 1.45 (σ = ln([H4SiO4]/Ksp)), silica nucleates on carboxyl-terminated areas of the surface, that are less than 30 nm in diameter. The nuclei evolve during early stages of growth to spread over the surface into a sheet like form.

  2. Methods for assessment of innovative medical technologies during early stages of development.

    PubMed

    Bartelmes, Marc; Neumann, Ulrike; Lühmann, Dagmar; Schönermark, Matthias P; Hagen, Anja

    2009-11-05

    Conventional Health Technology Assessment (HTA) is usually conducted at a point in time at which the development of the respective technology may no longer be influenced. By this time developers and/or purchasers may have misinvested resources. Thus the demand for Technology Assessment (TA) which incorporates appropriate methods during early development stages of a technology becomes apparent. Against this health political background, the present report describes methods for a development-accompanying assessment of innovative medical technologies. Furthermore, international research programmes set out to identify or apply such methods will be outlined. A systematic literature search as well as an extensive manual literature search are carried out in order to obtain literature and information. The greatest units of the identified methods consist of assessment concepts, decision support methods, modelling approaches and methods focusing on users and their knowledge. Additionally, several general-purpose concepts have been identified. The identified research programmes INNO-HTA and MATCH (Multidisciplinary-Assessment-of-Technology-Centre-for-Healthcare) are to be seen as pilot projects which so far have not been able to generate final results. MATCH focuses almost entirely on the incorporation of the user-perspective regarding the development of non-pharmaceutical technologies, whereas INNO-HTA is basically concerned with the identification and possible advancement of methods for the early, socially-oriented technology assessment. Most references offer only very vague descriptions of the respective method and the application of greatly differing methods seldom exceeds the character of a pilot implementation. A standardisation much less an institutionalisation of development-accompanying assessment cannot be recognized. It must be noted that there is no singular method with which development-accompanying assessment should be carried out. Instead, a technology and

  3. Intraoperative Radiotherapy Versus Whole-Breast External Beam Radiotherapy in Early-Stage Breast Cancer

    PubMed Central

    Zhang, Li; Zhou, Zhirui; Mei, Xin; Yang, Zhaozhi; Ma, Jinli; Chen, Xingxing; Wang, Junqi; Liu, Guangyu; Yu, Xiaoli; Guo, Xiaomao

    2015-01-01

    Abstract There has not been a clear answer about the efficacy of intraoperative radiotherapy (IORT) for women with early-stage breast cancer. The aim of this meta-analysis was to summarize the available evidence comparing the efficacy and safety of IORT with those of whole-breast external beam radiotherapy (EBRT) for women with early-stage breast cancer. MEDLINE, EMBASE, the Web of Science, and the Cochrane Library were searched up to October 2014. Two authors independently conducted the literature selection and data extraction. Studies that compared IORT with whole-breast EBRT were included in the systematic review. IORT was defined as a single dose of irradiation to the tumor bed during breast-conserving surgery rather than whole-breast irradiation. Qualities of RCTs were evaluated according to the PEDro scale. Qualities of non-RCTs were evaluated according to the Methodological Index for Non-Randomized Studies (MINORS). The risk ratios (RRs) of ipsilateral breast tumor recurrence, overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were pooled using a random-effects model. Four studies with 5415 patients were included in this meta-analysis, including 2 randomized controlled trials (RCTs) and 2 non-RCTs. Ipsilateral breast tumor recurrence was significantly higher in patients with IORT compared to those with whole-breast EBRT (RR 2.83, 95% CI 1.23–6.51), but with significant heterogeneity (I2 = 58.5%, P = 0.065). Comparing IORT with whole-breast EBRT, the pooled RRs for overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were 0.88 (95% CI: 0.66–1.17), 1.20 (95% CI: 0.77–1.86), 0.76 (95% CI: 0.44–1.31), and 0.95 (95% CI: 0.61–1.49), respectively. IORT had a significantly higher risk of ipsilateral breast tumor recurrence than whole-breast EBRT. Overall mortality did not differ significantly. IORT should be used in conjunction with the prudent selection of

  4. Clinically Defined Type 2 Diabetes Mellitus and Prognosis in Early-Stage Breast Cancer

    PubMed Central

    Erickson, Kirsten; Patterson, Ruth E.; Flatt, Shirley W.; Natarajan, Loki; Parker, Barbara A.; Heath, Dennis D.; Laughlin, Gail A.; Saquib, Nazmus; Rock, Cheryl L.; Pierce, John P.

    2011-01-01

    Purpose Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis. Methods Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival. Results Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (Ptrend < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk. Conclusion Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted. PMID:21115861

  5. Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

    ClinicalTrials.gov

    2015-09-02

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

  6. Proteomics Identification of Potential Candidates Involved in Cell Proliferation for Early Stage of Brain Regeneration in the Adult Zebrafish.

    PubMed

    Lim, Fei Tieng; Ogawa, Satoshi; Smith, A Ian; Parhar, Ishwar S

    2017-02-01

    The central nervous system (CNS) of the non-mammalian vertebrates has better neuroregenerative capability as compared with the mammalian CNS. Regeneration of habenula was observed 40 days after damage in zebrafish. During the early stage of regeneration, we found a significant increase of apoptotic cells on day-1 post-damage and of proliferative cells on day-3 post-damage. To identify the molecular factor(s) involved in the early stages of neuroregeneration, differentially expressed proteins during sham, 20- and 40-h post-habenula damage were investigated by proteomic approach by using two-dimensional differential gel electrophoresis (2D-DIGE) coupled with Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight (MALDI-ToF) and tandem mass spectrometry. Protein profiles revealed 17 differentially (>1.5-fold) expressed proteins: 10 upregulated, 4 downregulated, 2 proteins were found to be downregulated at the early stage but upregulated at a later stage, and 1 protein was found to be upregulated at 2 different time points. All proteins identified can be summarized under few molecular processes involved in the early stages of neuroregeneration in zebrafish CNS: apoptosis regulation (Wnt inhibitory factor 1 [WIF1]), neuroprotection (metallothionein), cell proliferation (Spred2, ependymin, Lhx1, and Wnts), differentiation (Spred2, Lhx9, and Wnts), and morphogenesis (cytoplasmic actins and draculin). These protein profiling results suggest that drastic molecular changes occur in the neuroregenerative process during this period, which includes cell proliferation, differentiation, and protection.

  7. Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

    PubMed

    Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

    2014-12-01

    In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

  8. Interaction between Streptococcus spp. and Veillonella tobetsuensis in the Early Stages of Oral Biofilm Formation

    PubMed Central

    Mashima, Izumi

    2015-01-01

    Dental plaque is a multispecies oral biofilm, the development of which is initiated by adherence of the pioneer Streptococcus spp. Oral Veillonella spp., including V. atypica, V. denticariosi, V. dispar, V. parvula, V. rogosae, and V. tobetsuensis, are known as early colonizers in oral biofilm formation. These species have been reported to coaggregate with Streptococcus spp. in a metabolic cooperation-dependent manner to form biofilms in human oral cavities, especially in the early stages of biofilm formation. However, in our previous study, Streptococcus gordonii showed biofilm formation to the greatest extent in the presence of V. tobetsuensis, without coaggregation between species. These results suggest that V. tobetsuensis produces signaling molecules that promote the proliferation of S. gordonii in biofilm formation. It is well known in many bacterial species that the quorum-sensing (QS) system regulates diverse functions such as biofilm formation. However, little is known about the QS system with autoinducers (AIs) with respect to Veillonella and Streptococcus spp. Recently, autoinducer 1 (AI-1) and AI-2 were detected and identified in the culture supernatants of V. tobetsuensis as strong signaling molecules in biofilm formation with S. gordonii. In particular, the supernatant from V. tobetsuensis showed the highest AI-2 activity among 6 oral Veillonella species, indicating that AIs, mainly AI-2, produced by V. tobetsuensis may be important factors and may facilitate biofilm formation of S. gordonii. Clarifying the mechanism that underlies the QS system between S. gordonii and V. tobetsuensis may lead to the development of novel methods for the prevention of oral infectious diseases caused by oral biofilms. PMID:25917902

  9. Gold nanoparticle-enabled blood test for early stage cancer detection and risk assessment.

    PubMed

    Zheng, Tianyu; Pierre-Pierre, Nickisha; Yan, Xin; Huo, Qun; Almodovar, Alvin J O; Valerio, Felipe; Rivera-Ramirez, Inoel; Griffith, Elizabeth; Decker, David D; Chen, Sixue; Zhu, Ning

    2015-04-01

    When citrate ligands-capped gold nanoparticles are mixed with blood sera, a protein corona is formed on the nanoparticle surface due to the adsorption of various proteins in the blood to the nanoparticles. Using a two-step gold nanoparticle-enabled dynamic light scattering assay, we discovered that the amount of human immunoglobulin G (IgG) in the gold nanoparticle protein corona is increased in prostate cancer patients compared to noncancer controls. Two pilot studies conducted on blood serum samples collected at Florida Hospital and obtained from Prostate Cancer Biorespository Network (PCBN) revealed that the test has a 90-95% specificity and 50% sensitivity in detecting early stage prostate cancer, representing a significant improvement over the current PSA test. The increased amount of human IgG found in the protein corona is believed to be associated with the autoantibodies produced in cancer patients as part of the immunodefense against tumor. Proteomic analysis of the nanoparticle protein corona revealed molecular profile differences between cancer and noncancer serum samples. Autoantibodies and natural antibodies produced in cancer patients in response to tumorigenesis have been found and detected in the blood of many cancer types. The test may be applicable for early detection and risk assessment of a broad spectrum of cancer. This new blood test is simple, low cost, requires only a few drops of blood sample, and the results are obtained within minutes. The test is well suited for screening purpose. More extensive studies are being conducted to further evaluate and validate the clinical potential of the new test.

  10. Geological, isothermal, and isobaric 3-D model construction in early stage of geothermal exploration

    NASA Astrophysics Data System (ADS)

    Saputra, M. P.; Suryantini; Catigtig, D.; Regandara, R.; Asnin, S. N.; Pratama, A. B.

    2016-09-01

    Construction of geology, thermal anomaly and pressure distribution of a geothermal system in the early stage of exploration where data is limited is described using a 3-D software, Leapfrog Geothermal. The geological 3-D model was developed from a topographic map (derived from DEM data), geological map and literature studies reported in an early geological survey. The isothermal 3-D model was constructed using reservoir temperature estimation from geothermometry calculated from chemical analyses on surface manifestations, available shallow gradient temperature hole data and the normal gradient temperature (3°C/100m) for a nonthermal area. The isobaric 3-D model was built using hydrostatic pressure where the hydrostatic pressure is determined by the product of the fluid density, acceleration due to gravity, and depth. Fluid density is given by saturated liquid density as a function of temperature. There are some constraints on the modelling result such as (1) within the predicted reservoir, the geothermal gradient is not constant but continues to increase, thus, creating an anomalously high temperature at depth, and (2) the lithology model is made by interpolating and extrapolating cross-sections whereas usually only two to three geology sections were available for this study. Hence, the modeller must understand the geology. An additional cross section was developed by the modeller which may not be as suitable as the geologist constructed sections. The results of this study can be combined with geophysical data such as gravity, geomagnetic, micro-tremor and resistivity data. The combination of geological, geochemical, isothermal, isobaric and geophysical data could be used in (1) estimating the geometry and size of the geothermal reservoir, (2) predicting the depth of top reservoir, and (3) creating well prognosis for exploration and production wells.

  11. Harvey Cushing and pediatric brain tumors at Johns Hopkins: the early stages of development

    PubMed Central

    Pendleton, Courtney; Ahn, Edward S.; Quiñones-Hinojosa, Alfredo

    2015-01-01

    Object Harvey Cushing, credited with pioneering the field of neurosurgery as a distinct surgical subspecialty in the US, was at the forefront of neurooncology, publishing seminal papers on the diagnosis and treatment of pediatric brain tumors during the latter part of his career. However, his contributions to the surgical treatment of these lesions during the early stages of his tenure at the Johns Hopkins Hospital, from 1896 to 1912, remain largely unknown. Methods After obtaining institutional review board approval, and through the courtesy of the Alan Mason Chesney Archives, the authors reviewed the Johns Hopkins Hospital surgical files from the years 1896 to 1912. Patients younger than 18 years of age, presenting with symptoms suspicious for an intracranial tumor, and undergoing surgical intervention by Cushing were selected for further analysis. Results Of the 40 pediatric patients undergoing surgery for suspected intracranial neoplasms, 26 were male. The mean age among the entire sample was 10.1 years. Cushing used three main operative approaches in the surgical treatment of pediatric intracranial neoplasms: infratentorial/suboccipital, subtemporal, and hemisphere flap. Twenty-three patients had negative findings following both the primary and subsequent surgical interventions conducted by Cushing. Postoperative conditions following the primary surgical intervention were improved in 24 patients. Twelve patients (30%) died during their inpatient stay for the primary intervention. The mean time to the last follow-up was 24.9 months; the mean time to death was 10.0 months. Conclusions Cushing strove to maximize exposure while minimizing blood loss in an attempt to increase his ability to successfully treat pediatric brain tumors. His early contributions to the field of pediatric neurooncology demonstrate his commitment to advancing the field of neurosurgery. PMID:21631192

  12. Oxygen consumption rate and Na+/K+-ATPase activity in early developmental stages of the sea urchin Paracentrotus lividus Lam.

    NASA Astrophysics Data System (ADS)

    Tomšić, Sanja; Stanković, Suzana; Lucu, Čedomil

    2011-09-01

    Changes in oxygen consumption rate and Na+/K+-ATPase activity during early development were studied in the sea urchin Paracentrotus lividus Lam. The oxygen consumption rate increased from 0.12 μmol O2 mg protein-1 h-1 in unfertilized eggs to 0.38 μmol O2 mg protein-1 h-1 25 min after fertilization. Specific activity of the Na+/K+-ATPase was significantly stimulated after fertilization, ranging up to 1.07 μmol Pi h-1 mg protein-1 in the late blastula stage and slightly lower values in the early and late pluteus stages.

  13. Chromium Toxicity Test for Fall Chinook Salmon (Oncorhynchus tshawytscha) Using Hanford Site Groundwater: Onsite Early Life-Stage Toxicity Evaluation

    SciTech Connect

    Patton, Gregory W.; Dauble, Dennis D.; Chamness, Michele A.; Abernethy, Cary S.; McKinstry, Craig A.

    2001-07-10

    The objective of this study was to evaluate site-specific effects for early life-stage (eyed eggs to free swimming juveniles) fall chinook salmon that might be exposed to hexavalent chromium from Hanford groundwater sources. Our exposure conditions included hexavalent chromium obtained from Hanford groundwater wells near the Columbia River, Columbia River water as the diluent, and locally adapted populations of fall chinook salmon. This report describes both a 96-hr pretest using rainbow trout eggs and an early life-stage test beginning with chinook salmon eggs.

  14. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    PubMed

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving.

  15. The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

    PubMed

    Fleming, Jonathan J

    2015-02-01

    A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas.

  16. The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE

    PubMed Central

    Kim, Jung Hee; Sinn, Dong Hyun; Shin, Sung Wook; Cho, Sung Ki; Kang, Wonseok; Gwak, Geum-Youn; Paik, Yong-Han; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Choi, Moon Seok

    2017-01-01

    Background/Aims We investigated the outcomes of early-stage hepatocellular carcinoma (HCC) patients who showed a complete response (CR) to initial transarterial chemoembolization (TACE), with a focus on the role of scheduled TACE repetition. Methods A total of 178 patients with early-stage HCC who were initially treated with TACE and showed a CR based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria on one month follow-up computed tomography (CT) were analyzed. Among them, 90 patients underwent scheduled repetition of TACE in the absence of viable tumor on CT. Results During a median follow-up period of 4.6 years (range: 0.4-8.8 years), mortality was observed in 71 patients (39.9%). The overall recurrence-free and local recurrence-free survival rates at 1 year were 44.4% and 56.2%. In the multivariable model, scheduled repetition of TACE was an independent factor associated with survival (hazard ratio [95% confidence interval]: 0.56 [0.34-0.93], P=0.025). When stratified using Barcelona clinic liver cancer (BCLC) stage, scheduled repetition of TACE was associated with a favorable survival rate in BCLC stage A patients, but not in BCLC 0 patients. Conclusions Scheduled repetition of TACE was associated with better survival for early-stage HCC patients showing a CR after initial TACE, especially in BCLC stage A patients. PMID:28263954

  17. Early lactation feed intake and milk yield responses of dairy cows offered grass silages harvested at early maturity stages.

    PubMed

    Randby, A T; Weisbjerg, M R; Nørgaard, P; Heringstad, B

    2012-01-01

    The main objective was to evaluate the potential of grass silages of very high quality to support a high milk yield with a low or moderate, or even without concentrate supplementation. Production responses to increased levels of concentrate supplementation with 3 primary growth grass silages differing in digestibility were studied using 66 Norwegian Red dairy cows. Roundbale silage was produced from a timothy-dominated sward at very early (H1), early (H2), and normal (H3) stages of crop maturity. Crops were rapidly wilted (<24h) and a formic acid-based additive was applied. All silages were restrictedly fermented. Silage digestible organic matter in dry matter (DM) values were 747, 708, and 647 g/kg of DM for H1, H2, and H3, respectively. Dietary treatments were fed in a 3×3 factorial arrangement of the 3 silages supplemented with 3 concentrate levels (4, 8, and 12 kg/d) and, additionally, H1 was offered without concentrates and H3 with 16 kg/d, giving a total of 11 diets. Cows, blocked according to parity and calving date, were introduced to the experiment before calving and kept in the experiment until wk 16 of lactation. Silage was offered ad libitum in loose housing and concentrate was available in automatic feed stations. Intake of grass silage when fed as the sole feed was 16.9 kg of DM on average for lactation wk 1 to 16. When H1 was supplemented with 4 or 8 kg of concentrates, silage DM intake did not change, but total DM intake increased to 20.6 and 23.7 kg/d, respectively. Energy-corrected milk (ECM) yield increased from 23.4 kg when H1 was offered without concentrate supplement to 29.1 and 32.8 kg when supplemented with 4 or 8 kg concentrate, respectively. None of the other diets equaled the yield obtained by H1 plus 8 kg of concentrate. Feed intake and yield of cows offered H3 plus 4 kg of concentrates were strongly constrained by high dietary fiber concentration. They consumed 16.5 g of neutral detergent fiber/kg of body weight and spent more time

  18. Tough Adults, Frail Babies: An Analysis of Stress Sensitivity across Early Life-History Stages of Widely Introduced Marine Invertebrates

    PubMed Central

    Pineda, M. Carmen; McQuaid, Christopher D.; Turon, Xavier; López-Legentil, Susanna; Ordóñez, Víctor; Rius, Marc

    2012-01-01

    All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be

  19. Tough adults, frail babies: an analysis of stress sensitivity across early life-history stages of widely introduced marine invertebrates.

    PubMed

    Pineda, M Carmen; McQuaid, Christopher D; Turon, Xavier; López-Legentil, Susanna; Ordóñez, Víctor; Rius, Marc

    2012-01-01

    All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be

  20. Investigating Alternatives to the Fish Early Life-Stage Test: A Strategy for Discovering and Annotating Adverse Outcome Pathways for Early Fish Development

    EPA Science Inventory

    The fish early life-stage (FELS) test (OECD Test Guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an on-going effort to develop efficient and cost-effec...

  1. Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

    PubMed

    Shemenski, Justin

    2016-04-09

    potential immunomodulator. CIM therapy has been shown to increase levels of the TH1 associated cytokines IL-12, TNF-α, and IFN-γ while decreasing levels of the TH2 associated cytokine IL-10. The author proposes a novel theory that CIM therapy during early Bb infection may promote a more appropriate immune response and increase the utility of antibiotic therapy during early stage Lyme disease, thus improving clinical outcomes of the disease.

  2. Effect of ocean warming and acidification on the early life stages of subtropical Acropora spicifera

    NASA Astrophysics Data System (ADS)

    Foster, T.; Gilmour, J. P.; Chua, C. M.; Falter, J. L.; McCulloch, M. T.

    2015-12-01

    This study investigated the impacts of acidified seawater ( pCO2 ~ 900 μatm) and elevated water temperature (+3 °C) on the early life history stages of Acropora spicifera from the subtropical Houtman Abrolhos Islands (28°S) in Western Australia. Settlement rates were unaffected by high temperature (27 °C, ~250 μatm), high pCO2 (24 °C, ~900 μatm), or a combination of both high temperature and high pCO2 treatments (27 °C, ~900 μatm). There were also no significant differences in rates of post-settlement survival after 4 weeks of exposure between any of the treatments, with survival ranging from 60 to 70 % regardless of treatment. Similarly, calcification, as determined by the skeletal weight of recruits, was unaffected by an increase in water temperature under both ambient and high pCO2 conditions. In contrast, high pCO2 significantly reduced early skeletal development, with mean skeletal weight in the high pCO2 and combined treatments reduced by 60 and 48 %, respectively, compared to control weights. Elevated temperature appeared to have a partially mitigative effect on calcification under high pCO2; however, this effect was not significant. Our results show that rates of settlement, post-settlement survival, and calcification in subtropical corals are relatively resilient to increases in temperature. This is in marked contrast to the sensitivity to temperature reported for the majority of tropical larvae and recruits in the literature. The subtropical corals in this study appear able to withstand an increase in temperature of 3 °C above ambient, indicating that they may have a wider thermal tolerance range and may not be adversely affected by initial increases in water temperature from subtropical 24 to 27 °C. However, the reduction in skeletal weight with high pCO2 indicates that early skeletal formation will be highly vulnerable to the changes in ocean pCO2 expected to occur over the twenty-first century, with implications for their longer-term growth

  3. Early stage breast cancer detection by means of time-domain ultra-wide band sensing

    NASA Astrophysics Data System (ADS)

    Zanoon, T. F.; Abdullah, M. Z.

    2011-11-01

    The interest in the use of ultra-wide band (UWB) impulses for medical imaging, particularly early stage breast cancer detection, is driven by safety advantage, super resolution capability, significant dielectric contrast between tumours and their surrounding tissues, patient convenience and low operating costs. However, inversion algorithms leading to recovery of the dielectric profile are complex in their nature, and vulnerable to noisy experimental conditions and environment. In this paper, we present a simplified yet robust gradient-based iterative image reconstruction technique to solve the nonlinear inverse scattering problem. The calculation is based on the Polak-Ribière's approach while the Broyden's formula is used to update the gradient in an iterative scheme. To validate this approach, both numerical and experimental results are presented. Animal derived biological targets in the form of chicken skin, beef and salted butter are used to construct an experimental breast phantom, while vegetable oil is used as a background media. UWB transceivers in the form of biconical antennas contour the breast forming a full view scanning geometry at a frequency range of 0-5 GHz. Results indicate the feasibility of experimental detection of millimetre scaled targets.

  4. Microstructural evolution at the bonding interface during the early-stage infrared active brazing of alumina

    NASA Astrophysics Data System (ADS)

    Shiue, R. K.; Wu, S. K.; O, J. M.; Wang, J. Y.

    2000-10-01

    Infrared brazing of Al2O3 and alloy 42 using a silver-base active braze alloy was investigated at 900 °C for 0 to 300 seconds, with a heating rate of 3000 °C/min. Experimental results show that Ti3(Cu, Al)3O intermetallic with various amounts of Al is observed in the reaction layer and plays an important role in the early stage of reactive wetting. A two-layer structure is observed at the reaction interface brazed at 900 °C for 5 seconds. The reaction layer close to the alumina contains large amounts of Al, so the mass balance of the system is maintained. The growth of the reaction layer is not rate controlled by diffusion within the first 120 seconds. After 120 seconds, the rate controlling mechanism of the reaction layer becomes the diffusion control, satisfying the parabolic law. Dynamic wetting angle measurements using a traditional vacuum furnace at the heating rate of 10 °C/min demonstrate that the wetting angle rapidly decreases within the first 150 seconds, especially 0 to 80 seconds, and eventually stabilizes after 600 seconds.

  5. Efficiency of eugenol as anesthetic for the early life stages of Nile tilapia (Oreochromis niloticus).

    PubMed

    Ribeiro, Paula A P; Miranda-Filho, Kleber C; Melo, Daniela C de; Luz, Ronald K

    2015-03-01

    In aquaculture, activities with anesthetic compounds are usually used in order to ensure the welfare of farmed fish, allowing handling out of water with decreased trauma by stress. Presently, there is no information about anesthetic action of eugenol in early life stages of Nile tilapia (Oreochromis niloticus). The objective of this study was to evaluate different concentrations of eugenol for larvae and juveniles of Nile tilapia. Sixty animals were used for each group of weight, group I = 0.02 g; group II = 0.08 g; group III = 0.22 g; group IV = 2.62 g; and group V = 11.64 g. The eugenol concentrations tested were 50, 75, 100, 125, 150 and 175 mg L-1. No mortality was reported during the tests with eugenol. Tilapia larvae with 0.02 g and juveniles around 11.64 g can be anesthetized with eugenol concentrations between 150 and 175 mg L-1, since they determine the shortest sedation time (23 and 72 seconds, for the group of lowest and highest weights, respectively).

  6. Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

    PubMed

    De Sanctis, Vitaliana; Agolli, Linda; Visco, Vincenzo; Monaco, Flavia; Muni, Roberta; Spagnoli, Alessandra; Campanella, Barbara; Valeriani, Maurizio; Minniti, Giuseppe; Osti, Mattia F; Amanti, Claudio; Pellegrini, Patrizia; Brunetti, Serena; Costantini, Anna; Alfò, Marco; Torrisi, Maria Rosaria; Marchetti, Paolo; Enrici, Riccardo Maurizi

    2014-01-01

    We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

  7. αβ'-NAC cooperates with Sam37 to mediate early stages of mitochondrial protein import.

    PubMed

    Ponce-Rojas, José Carlos; Avendaño-Monsalve, Maria Clara; Yañez-Falcón, Armando Roberto; Jaimes-Miranda, Fabiola; Garay, Erika; Torres-Quiroz, Francisco; DeLuna, Alexander; Funes, Soledad

    2017-03-01

    The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial subcompartments until they reach their functional destination. It has been suggested that the nascent-polypeptide associated complex (NAC) - a cytosolic chaperone that recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated cotranslational import are still not clear. Here, we show that a particular NAC heterodimer formed by subunits α and β' in Saccharomyces cerevisiae is specifically involved in the process of mitochondrial import and functionally cooperates with Sam37, an outer membrane protein subunit of the sorting and assembly machinery complex. Mutants in both components display growth defects, incorrectly accumulate precursor forms of mitochondrial proteins in the cytosol, and have an altered mitochondrial protein content. We propose that αβ'-NAC and Sam37 are members of the system that recognizes mitochondrial proteins at early stages of their synthesis, escorting them to the import machinery of mitochondria.

  8. Early-stage lupus nephritis treated with N-acetylcysteine: A report of two cases.

    PubMed

    Li, Ming; Gao, Wenjuan; Ma, Jingjing; Zhu, Yun; Li, Xingfu

    2015-08-01

    The oxidative-antioxidative status is closely associated with the progression of systemic lupus erythematosus (SLE), and oxidative stress is customarily found in patients with SLE. N-acetylcysteine (NAC), a typical antioxidant, is reliable and often applied for clinical treatment. Lupus nephritis (LN) is a kidney disorder associated with SLE, but the treatment of LN with antioxidants is rarely documented. The present report describes two cases of early-stage LN that were orally treated with 1,200 mg NAC in addition to the standard therapy with hydroxychloroquine and calcitriol. Following the NAC administration, the glutathione level largely increased while the level of the lipid peroxidation biomarker 8-iso-prostaglandin F2α declined in both cases. In addition, the routine blood counts, 24-h urine protein, erythrocyte sedimentation rate and the SLE disease activity index were markedly improved. In conclusion, the present report of two cases has shown that NAC, as an antioxidant, may exert a beneficial effect to modulate the oxidative status in LN; however, the underlying mechanisms require further investigation.

  9. Early-stage lupus nephritis treated with N-acetylcysteine: A report of two cases

    PubMed Central

    LI, MING; GAO, WENJUAN; MA, JINGJING; ZHU, YUN; LI, XINGFU

    2015-01-01

    The oxidative-antioxidative status is closely associated with the progression of systemic lupus erythematosus (SLE), and oxidative stress is customarily found in patients with SLE. N-acetylcysteine (NAC), a typical antioxidant, is reliable and often applied for clinical treatment. Lupus nephritis (LN) is a kidney disorder associated with SLE, but the treatment of LN with antioxidants is rarely documented. The present report describes two cases of early-stage LN that were orally treated with 1,200 mg NAC in addition to the standard therapy with hydroxychloroquine and calcitriol. Following the NAC administration, the glutathione level largely increased while the level of the lipid peroxidation biomarker 8-iso-prostaglandin F2α declined in both cases. In addition, the routine blood counts, 24-h urine protein, erythrocyte sedimentation rate and the SLE disease activity index were markedly improved. In conclusion, the present report of two cases has shown that NAC, as an antioxidant, may exert a beneficial effect to modulate the oxidative status in LN; however, the underlying mechanisms require further investigation. PMID:26622376

  10. Lower hypoxia thresholds of cuttlefish early life stages living in a warm acidified ocean.

    PubMed

    Rosa, Rui; Trübenbach, Katja; Repolho, Tiago; Pimentel, Marta; Faleiro, Filipa; Boavida-Portugal, Joana; Baptista, Miguel; Lopes, Vanessa M; Dionísio, Gisela; Leal, Miguel Costa; Calado, Ricardo; Pörtner, Hans O

    2013-10-07

    The combined effects of future ocean acidification and global warming on the hypoxia thresholds of marine biota are, to date, poorly known. Here, we show that the future warming and acidification scenario led to shorter embryonic periods, lower survival rates and the enhancement of premature hatching in the cuttlefish Sepia officinalis. Routine metabolic rates increased during the embryonic period, but environmental hypercapnia significantly depressed pre-hatchling's energy expenditures rates (independently of temperature). During embryogenesis, there was also a significant rise in the carbon dioxide partial pressure in the perivitelline fluid (PVF), bicarbonate levels, as well as a drop in pH and oxygen partial pressure (pO₂). The critical partial pressure (i.e. hypoxic threshold) of the pre-hatchlings was significantly higher than the PVF oxygen partial pressure at the warmer and hypercapnic condition. Thus, the record of oxygen tensions below critical pO₂ in such climate scenario indicates that the already harsh conditions inside the egg capsules are expected to be magnified in the years to come, especially in populations at the border of their thermal envelope. Such a scenario promotes untimely hatching and smaller post-hatching body sizes, thus challenging the survival and fitness of early life stages.

  11. Impacts of treated municipal wastewaters on early life stages of fishes

    SciTech Connect

    Weis, P. ); Weis, J.S. ); Greenberg, A. )

    1988-09-01

    The Hudson-Raritan Estuary is a typical urban estuary that receives a tremendous burden of pollutants from many point- and non-point sources. Treated municipal wastewater (TMW) accounts for about 13% of the freshwater input, 90% of point-source volume and >98% of point-source pollutants. Most sources of TMW have a substantial industrial input, so the effluents include organics and heavy metals. While secondary treatment substantially reduces TMW toxicity, chlorination of the effluent restores the toxicity by producing oxidized and chlorinated compounds not previously present. The authors are attempting to assess the biological impacts of such effluents. They report here results to date of laboratory analyses of realistic dilutions of such secondarily-treated and chlorinated TMW. They have targeted three species of fish common to the Hudson-Raritan Estuary, the winter flounder (Pseudopleuonectes americanus), the mummichog (Fundulus heteroclitus) and the striped bass (Morone saxatilis). The estuary is a spawning area for the first two species and a significant overwintering area for the third, a protected species. Because the early life stages of fish are especially sensitive, they are focusing on development and growth.

  12. Neoadjuvant Therapy for Early-Stage Breast Cancer: Current Practice, Controversies, and Future Directions.

    PubMed

    Santa-Maria, Cesar Augusto; Camp, Melissa; Cimino-Mathews, Ashley; Harvey, Susan; Wright, Jean; Stearns, Vered

    2015-11-01

    Research in the fields of surgical, medical, and radiation oncology has changed the landscape of neoadjuvant therapy in breast cancer, yet many areas of controversy still exist. When considering whether a patient is a candidate for neoadjuvant therapy, ideally the initial assessment should be multidisciplinary in nature and should include clinical, radiographic, and pathologic evaluation. Optimization of systemic therapy is dependent upon identifying the patient's breast cancer subtype; the best approach may include targeted agents, as well as the determination of eligibility for enrollment into clinical trials that incorporate novel therapeutics or predictive biomarkers. This article will review a variety of surgical and radiation-based strategies for management of early-stage breast cancer, including surgical options involving the breast and axilla, and the role of radiation based on response to systemic therapy. Key areas of controversy include the ideal systemic treatment for different breast cancer subtypes, the surgical and radiotherapeutic approaches for management of the axilla, and the role of pathologic response rates as a surrogate for survival in drug development.

  13. Lipid droplet dynamics at early stages of Mycobacterium marinum infection in Dictyostelium.

    PubMed

    Barisch, Caroline; Paschke, Peggy; Hagedorn, Monica; Maniak, Markus; Soldati, Thierry

    2015-09-01

    Lipid droplets exist in virtually every cell type, ranging not only from mammals to plants, but also to eukaryotic and prokaryotic unicellular organisms such as Dictyostelium and bacteria. They serve among other roles as energy reservoir that cells consume in times of starvation. Mycobacteria and some other intracellular pathogens hijack these organelles as a nutrient source and to build up their own lipid inclusions. The mechanisms by which host lipid droplets are captured by the pathogenic bacteria are extremely poorly understood. Using the powerful Dictyostelium discoideum/Mycobacterium marinum infection model, we observed that, immediately after their uptake, lipid droplets translocate to the vicinity of the vacuole containing live but not dead mycobacteria. Induction of lipid droplets in Dictyostelium prior to infection resulted in a vast accumulation of neutral lipids and sterols inside the bacterium-containing compartment. Subsequently, under these conditions, mycobacteria accumulated much larger lipid inclusions. Strikingly, the Dictyostelium homologue of perilipin and the murine perilipin 2 surrounded bacteria that had escaped to the cytosol of Dictyostelium or microglial BV-2 cells respectively. Moreover, bacterial growth was inhibited in Dictyostelium plnA knockout cells. In summary, our results provide evidence that mycobacteria actively manipulate the lipid metabolism of the host from very early infection stages.

  14. Effects of CO2-driven ocean acidification on early life stages of marine medaka (Oryzias melastigma)

    NASA Astrophysics Data System (ADS)

    Mu, J.; Jin, F.; Wang, J.; Zheng, N.; Cong, Y.

    2015-06-01

    The potential effects of high CO2 and associated ocean acidification (OA) in marine fishes and other non-calcified organisms are less well understood. In this study, we investigated the responses of early life stages (ELS) of marine medaka (Oryzias melastigma) exposed to a series of experimental manipulation of CO2 levels. Results showed that CO2-driven seawater acidification (pH 7.6 and pH 7.2) had no detectable effect on hatching time, hatching rate, or heart rate of embryos. However, the deformity rate of larvae in the pH 7.2 treatment was significantly higher than that in the control treatment. There is no significant difference between the left and right otolith areas in each treatment. However, the average otolith area of larvae in the pH 7.6 treatment was significantly smaller than that in the control. Such alterations in the developmental abnormalities and otolith size of marine medaka larvae due to elevated-CO2 levels suggests that this species will be increasingly challenged by future OA. Further studies of the impacts of OA on marine fish to assess whether or not the environmental influence in one generation can affect the later life history and the phenotype of subsequent generations are needed.

  15. Effects of CO2-driven ocean acidification on early life stages of marine medaka (Oryzias melastigma)

    NASA Astrophysics Data System (ADS)

    Mu, J.; Jin, F.; Wang, J.; Zheng, N.; Cong, Y.

    2015-01-01

    The potential effects of elevated CO2 level and reduced carbonate saturation state in marine environment on fishes and other non-calcified organisms are still poorly known. In present study, we investigated the effects of ocean acidification on embryogenesis and organogenesis of newly hatched larvae of marine medaka (Oryzias melastigma) after 21 d exposure of eggs to different artificially acidified seawater (pH 7.6 and 7.2, respectively), and compared with those in control group (pH 8.2). Results showed that CO2-driven seawater acidification (pH 7.6 and 7.2) had no detectable effect on hatching time, hatching rate, and heart rate of embryos. However, the deformity rate of larvae in pH 7.2 treatment was significantly higher than that in control treatment. The left and right sagitta areas did not differ significantly from each other in each treatment. However, the mean sagitta area of larvae in pH 7.6 treatment was significantly smaller than that in the control (p = 0.024). These results suggest that although marine medaka might be more tolerant of elevated CO2 than some other fishes, the effect of elevated CO2 level on the calcification of otolith is likely to be the most susceptibly physiological process of pH regulation in early life stage of marine medaka.

  16. Histomorphometric Analysis of Cutaneous Remodeling in the Early Stage of the Scleroderma Model

    PubMed Central

    de Oliveira, Cristiane Carla; Velosa, Ana Paula Pereira; Parra, Edwin Roger; Capelozzi, Vera Luiza; Teodoro, Walcy Rosolia; Yoshinari, Natalino Hajime

    2009-01-01

    INTRODUCTION/OBJECTIVES Systemic sclerosis, or scleroderma, is a rheumatic disease characterized by autoimmunity, vasculopathy, and fibrosis of the skin and several internal organs. In the present study, our aim was to assess the skin alterations in animals with scleroderma during the first stages of disease induction. METHODS: To induce scleroderma, female New Zealand rabbits (n = 12) were subcutaneously immunized with 1 mg/ml of collagen V (Col V) in complete Freund’s adjuvant, twice with a thirty-day interval. Fifteen days later, the animals received an intramuscular booster with type V collagen in incomplete Freund’s adjuvant, twice with a fifteen-day interval. The control group was inoculated with 1 ml of 10 mM acetic acid solution diluted with an equal amount of Freund’s adjuvant. Serial dorsal skin biopsies were performed at 7, 15, and 30 days and stained with H&E, Masson’s trichrome and Picrosírius for morphological and morphometric analyses. RESULTS: Immunized rabbits presented a significant increase in collagen in skin collected seven days after the first immunization (p=0.05). CONCLUSION: The results from this experimental model may be very important to a better understanding of the pathogenic mechanisms involved in the beginning of human SSc. Therapeutic protocols to avoid early remodeling of the skin may lead to promising treatments for SSc in the future. PMID:19578663

  17. Early-stage Massive Star Formation near the Galactic Center: Sgr C

    NASA Astrophysics Data System (ADS)

    Kendrew, S.; Ginsburg, A.; Johnston, K.; Beuther, H.; Bally, J.; Cyganowski, C. J.; Battersby, C.

    2013-10-01

    We present near-infrared spectroscopy and 1 mm line and continuum observations of a recently identified site of high mass star formation likely to be located in the Central Molecular Zone (CMZ) near Sgr C. Located on the outskirts of the massive evolved H II region associated with Sgr C, the area is characterized by an Extended Green Object (EGO) measuring ~10'' in size (0.4 pc), whose observational characteristics suggest the presence of an embedded massive protostar driving an outflow. Our data confirm that early-stage star formation is taking place on the periphery of the Sgr C H II region, with detections of two protostellar cores and several knots of H2 and Brackett γ emission alongside a previously detected compact radio source. We calculate the cores' joint mass to be ~103 M ⊙, with column densities of 1-2 × 1024 cm-2. We show the host molecular cloud to hold ~105 M ⊙ of gas and dust with temperatures and column densities favorable for massive star formation to occur, however, there is no evidence of star formation outside of the EGO, indicating that the cloud is predominantly quiescent. Given its mass, density, and temperature, the cloud is comparable to other remarkable non-star-forming clouds such as G0.253 in the eastern CMZ.

  18. Fungal and algal gene expression in early developmental stages of lichen-symbiosis.

    PubMed

    Joneson, Suzanne; Armaleo, Daniele; Lutzoni, François

    2011-01-01

    How plants and microbes recognize each other and interact to form long-lasting relationships remains one of the central questions in cellular communication. The symbiosis between the filamentous fungus Cladonia grayi and the single-celled green alga Asterochloris sp. was used to determine fungal and algal genes upregulated in vitro in early lichen development. cDNA libraries of upregulated genes were created with suppression subtractive hybridization in the first two stages of lichen development. Quantitative PCR subsequently was used to verify the expression level of 41 and 33 candidate fungal and algal genes respectively. Induced fungal genes showed significant matches to genes putatively encoding proteins involved in self and non-self recognition, lipid metabolism, and negative regulation of glucose repressible genes, as well as to a putative d-arabitol reductase and two dioxygenases. Upregulated algal genes included a chitinase-like protein, an amino acid metabolism protein, a dynein-related protein and a protein arginine methyltransferase. These results also provided the first evidence that extracellular communication without cellular contact can occur between lichen symbionts. Many genes showing slight variation in expression appear to direct the development of the lichen symbiosis. The results of this study highlight future avenues of investigation into the molecular biology of lichen symbiosis.

  19. Nigericin is a potent inhibitor of the early stage of vaccinia virus replication.

    PubMed

    Myskiw, Chad; Piper, Jessica; Huzarewich, Rhiannon; Booth, Tim F; Cao, Jingxin; He, Runtao

    2010-12-01

    Poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. Thus, the identification of small molecule inhibitors of poxvirus replication is warranted. Vaccinia virus is the prototypic member of the Orthopoxvirus genus, which also includes variola and monkeypox virus. In this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia virus replication in several human cell lines. In HeLa cells, we found that the 50% inhibitory concentration of nigericin against vaccinia virus was 7.9 nM, with a selectivity index of 1038. We present data demonstrating that nigericin targets vaccinia virus replication at a post-entry stage. While nigericin moderately inhibits both early vaccinia gene transcription and translation, viral DNA replication and intermediate and late gene expression are severely compromised in the presence of nigericin. Our results demonstrate that nigericin has the potential to be further developed into an effective antiviral to treat poxvirus infections.

  20. Cross-modal re-organization in adults with early stage hearing loss.

    PubMed

    Campbell, Julia; Sharma, Anu

    2014-01-01

    Cortical cross-modal re-organization, or recruitment of auditory cortical areas for visual processing, has been well-documented in deafness. However, the degree of sensory deprivation necessary to induce such cortical plasticity remains unclear. We recorded visual evoked potentials (VEP) using high-density electroencephalography in nine persons with adult-onset mild-moderate hearing loss and eight normal hearing control subjects. Behavioral auditory performance was quantified using a clinical measure of speech perception-in-noise. Relative to normal hearing controls, adults with hearing loss showed significantly larger P1, N1, and P2 VEP amplitudes, decreased N1 latency, and a novel positive component (P2') following the P2 VEP. Current source density reconstruction of VEPs revealed a shift toward ventral stream processing including activation of auditory temporal cortex in hearing-impaired adults. The hearing loss group showed worse than normal speech perception performance in noise, which was strongly correlated with a decrease in the N1 VEP latency. Overall, our findings provide the first evidence that visual cross-modal re-organization not only begins in the early stages of hearing impairment, but may also be an important factor in determining behavioral outcomes for listeners with hearing loss, a finding which demands further investigation.

  1. Discovery of gramine derivatives that inhibit the early stage of EV71 replication in vitro.

    PubMed

    Wei, Yanhong; Shi, Liqiao; Wang, Kaimei; Liu, Manli; Yang, Qingyu; Yang, Ziwen; Ke, Shaoyong

    2014-06-27

    Enterovirus 71 (EV71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for EV71 infections. In this study, the antiviral activity of gramine and 21 gramine derivatives against EV71 was investigated in cell-based assays. Eighteen derivatives displayed some degree of inhibitory effects against EV71, in that they could effectively inhibit virus-induced cytopathic effects (CPEs), but the anti-EV71 activity of the lead compound gramine was not observed. Studies on the preliminary modes of action showed that these compounds functioned by targeting the early stage of the EV71 lifecycle after viral entry, rather than inactivating the virus directly, inhibiting virus adsorption or affecting viral release from the cells. Among these derivatives, one (compound 4s) containing pyridine and benzothiazole units showed the most potency against EV71. Further studies demonstrated that derivative 4s could profoundly inhibit viral RNA replication, protein synthesis, and virus-induced apoptosis in RD cells. These results indicate that derivative 4s might be a feasible therapeutic agent against EV71 infection and that these gramine derivatives may provide promising lead scaffolds for the further design and synthesis of potential antiviral agents.

  2. Re-examining the effects of verbal instructional type on early stage motor learning.

    PubMed

    Bobrownicki, Ray; MacPherson, Alan C; Coleman, Simon G S; Collins, Dave; Sproule, John

    2015-12-01

    The present study investigated the differential effects of analogy and explicit instructions on early stage motor learning and movement in a modified high jump task. Participants were randomly assigned to one of three experimental conditions: analogy, explicit light (reduced informational load), or traditional explicit (large informational load). During the two-day learning phase, participants learned a novel high jump technique based on the 'scissors' style using the instructions for their respective conditions. For the single-day testing phase, participants completed both a retention test and task-relevant pressure test, the latter of which featured a rising high-jump-bar pressure manipulation. Although analogy learners demonstrated slightly more efficient technique and reported fewer technical rules on average, the differences between the conditions were not statistically significant. There were, however, significant differences in joint variability with respect to instructional type, as variability was lowest for the analogy condition during both the learning and testing phases, and as a function of block, as joint variability decreased for all conditions during the learning phase. Findings suggest that reducing the informational volume of explicit instructions may mitigate the deleterious effects on performance previously associated with explicit learning in the literature.

  3. Intraoperative localization of early-stage gastrointestinal tumors using a marking clip detector system.

    PubMed

    Ohdaira, Takeshi; Nagai, Hideo; Shibusawa, Hiroyuki

    2005-01-01

    Intraoperative Tumor site recognition is extremely difficult during laparoscopic surgical treatment of early-stage gastrointestinal carcinoma. A novel marking method that uses both metallic clips and a marking clip detector system (MCDS, Olympus Optical Co., Tokyo, Japan) modified from a metal detector system, was designed by the authors. Metallic clips were applied to the tumor site during preoperative endoscopy, and the clip site was identified intraoperatively using the MCDS. In a basic ex vivo study, three metallic clips were detected easily (100% detection). In a clinical study, the marking site was detected in all gastric cancer patients who underwent laparoscopic subtotal gastrectomy. The mean distance between detected site and clip along the longitudinal bowel axis was 6.4 +/- 2.9 mm. Mean detection time was 18.1 +/- 5.7 seconds. None of the patients in this study experienced complications from this marking technique. MCDS allows accurate identification of tumor sites. This method may be useful for tumor